id
stringlengths 1
4
| tokens
sequence | ner_tags
sequence |
---|---|---|
0 | [
"Levofloxacin",
"for",
"prophylaxis",
"in",
"breast",
"cancer",
"surgery",
"compared",
"with",
"ofloxacin",
".",
"We",
"found",
"that",
"once",
"-",
"daily",
"use",
"of",
"ofloxacin",
"is",
"beneficial",
"from",
"the",
"standpoints",
"of",
"economy",
"and",
"patient",
"compliance",
".",
"Levofloxacin",
",",
"has",
"twice",
"the",
"antimicrobial",
"activity",
"and",
"same",
"toxicity",
"of",
"ofloxacin",
".",
"We",
"investigated",
"the",
"clinical",
"usefulness",
"of",
"levofloxacin",
"compared",
"with",
"ofloxacin",
"in",
"breast",
"surgery",
".",
"Between",
"July",
",",
"1996",
"and",
"April",
",",
"1999",
",",
"199",
"consecutive",
"patients",
"hospitalized",
"in",
"our",
"department",
"for",
"treatment",
"of",
"breast",
"cancer",
"were",
"enrolled",
"in",
"this",
"study",
"with",
"their",
"informed",
"consent",
"and",
"181",
"patients",
"were",
"evaluated",
".",
"Four",
"(",
"4",
"%",
")",
"of",
"the",
"99",
"patients",
"in",
"the",
"levofloxacin",
"group",
"had",
"wound",
"infections",
",",
"as",
"did",
"5",
"(",
"6",
"%",
")",
"of",
"the",
"82",
"patients",
"in",
"the",
"ofloxacin",
"group",
".",
"The",
"median",
"times",
"needed",
"for",
"wound",
"care",
",",
"with",
"25",
"th",
"and",
"75",
"th",
"percentiles",
",",
"were",
"13",
"[",
"9",
",",
"16",
"]",
"days",
"in",
"the",
"levofloxacin",
"group",
"and",
"11",
"[",
"9",
",",
"16",
"]",
"days",
"in",
"the",
"ofloxacin",
"group",
".",
"From",
"infected",
"wound",
"three",
"strains",
"of",
"Staphylococcus",
"aureus",
"were",
"detected",
"from",
"the",
"levofloxacin",
"group",
"and",
"two",
"strains",
"were",
"from",
"ofloxacin",
"group",
",",
"but",
"no",
"methicillin",
"-",
"resistant",
"strains",
"were",
"isolated",
".",
"Multiple",
"regression",
"analysis",
"showed",
"that",
"only",
"wound",
"dehiscence",
"was",
"a",
"significant",
"factor",
"in",
"the",
"occurrence",
"of",
"wound",
"infection",
"and",
"the",
"period",
"of",
"wound",
"care",
".",
"No",
"signs",
"or",
"symptoms",
"suggesting",
"levofloxacin",
"or",
"ofloxacin",
"toxicity",
"were",
"observed",
".",
"Laboratory",
"test",
"changes",
"before",
"and",
"after",
"treatment",
"were",
"similar",
"in",
"the",
"two",
"groups",
".",
"It",
"appears",
"that",
"levofloxacin",
"is",
"not",
"superior",
"to",
"ofloxacin",
"in",
"prophylactic",
"efficacy",
"for",
"postoperative",
"wound",
"infection",
"after",
"breast",
"surgery",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
27,
0,
31,
32,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
37,
0,
45,
0,
49,
0,
0,
0,
0,
0,
0,
0,
39,
0,
47,
0,
51,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
1 | [
"Effects",
"of",
"hydrochlorothiazide",
"on",
"drainage",
"volume",
"and",
"seroma",
"formation",
"in",
"deep",
"inferior",
"epigastric",
"perforator",
"flap",
"breast",
"reconstruction",
":",
"Randomized",
"controlled",
"trial",
".",
"Seroma",
"is",
"a",
"recognized",
"complication",
"encountered",
"at",
"the",
"reconstructed",
"breast",
"and",
"donor",
"site",
"after",
"abdominal",
"-",
"based",
"breast",
"reconstruction",
".",
"Seroma",
"is",
"caused",
"by",
"lymphatic",
"channel",
"disruption",
"and",
"the",
"formation",
"of",
"a",
"large",
"space",
"between",
"the",
"deep",
"fascia",
"during",
"flap",
"elevation",
".",
"Surgical",
"techniques",
"to",
"preserve",
"the",
"lymphatics",
"and",
"secure",
"the",
"closure",
"of",
"the",
"donor",
"site",
"can",
"reduce",
"seroma",
"formation",
".",
"This",
"study",
"investigated",
"the",
"safety",
"and",
"effectiveness",
"of",
"the",
"diuretic",
"hydrochlorothiazide",
"at",
"reducing",
"interstitial",
"fluid",
"accumulation",
"and",
"seroma",
"formation",
"during",
"deep",
"inferior",
"epigastric",
"perforator",
"(",
"DIEP",
")",
"flap",
"breast",
"reconstruction",
".",
"Sixty",
"patients",
"with",
"breast",
"cancer",
"who",
"underwent",
"skin-",
"or",
"nipple",
"-",
"sparing",
"mastectomy",
"and",
"DIEP",
"flap",
"reconstruction",
"were",
"enrolled",
"between",
"August",
"2016",
"and",
"June",
"2017",
".",
"The",
"patients",
"were",
"randomly",
"assigned",
"to",
"receive",
"either",
"25",
"mg",
"per",
"day",
"of",
"hydrochlorothiazide",
"from",
"the",
"second",
"to",
"the",
"twentieth",
"day",
"after",
"surgery",
"(",
"treatment",
")",
"or",
"no",
"diuretic",
"(",
"control",
")",
".",
"The",
"clinicopathological",
"characteristics",
",",
"drainage",
"time",
",",
"and",
"drainage",
"volume",
"were",
"statistically",
"compared",
"between",
"the",
"two",
"groups",
".",
"The",
"average",
"total",
"drainage",
"volume",
"at",
"the",
"donor",
"site",
"was",
"291",
"mL",
"in",
"the",
"treatment",
"group",
"and",
"434",
"mL",
"in",
"the",
"control",
"group",
"(",
"p",
"=",
"0.003",
")",
".",
"The",
"differences",
"in",
"body",
"mass",
"index",
"and",
"flap",
"weight",
"between",
"the",
"two",
"groups",
"were",
"not",
"statistically",
"significant",
"(",
"p",
"=",
"0.879",
"and",
"p",
"=",
"0.963",
",",
"respectively",
")",
".",
"No",
"hypotension",
"or",
"electrolyte",
"imbalance",
"was",
"noted",
"during",
"the",
"follow",
"-",
"up",
".",
"Intake",
"of",
"25",
"mg",
"per",
"day",
"of",
"hydrochlorothiazide",
"tablets",
"effectively",
"reduced",
"the",
"total",
"abdominal",
"drainage",
"volume",
"and",
"removal",
"time",
"of",
"indwelling",
"drains",
".",
"However",
",",
"the",
"adverse",
"effects",
"should",
"be",
"further",
"investigated",
"in",
"a",
"large",
"population",
"and",
"multiracial",
"cohort",
"before",
"using",
"hydrochlorothiazide",
"for",
"seroma",
"prevention",
"."
] | [
0,
0,
17,
0,
13,
14,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
33,
34,
0,
0,
0,
0,
0,
35,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
2 | [
"Prophylactic",
"use",
"of",
"levonorgestrel",
"-",
"releasing",
"intrauterine",
"system",
"in",
"women",
"with",
"breast",
"cancer",
"treated",
"with",
"tamoxifen",
":",
"a",
"randomized",
"controlled",
"trial",
".",
"To",
"estimate",
"the",
"rate",
"of",
"endometrial",
"pathology",
"with",
"the",
"prophylactic",
"use",
"of",
"levonorgestrel",
"-",
"releasing",
"intrauterine",
"system",
"in",
"women",
"with",
"breast",
"cancer",
"treated",
"with",
"tamoxifen",
".",
"This",
"was",
"a",
"randomized",
"contro",
"-",
"lled",
"trial",
"of",
"129",
"Chinese",
"women",
"who",
"attended",
"a",
"university",
"hospital",
"in",
"Hong",
"Kong",
"and",
"required",
"adjuvant",
"tamoxifen",
"for",
"breast",
"cancer",
"after",
"the",
"completion",
"of",
"postoperative",
"radiotherapy",
"and",
"chemotherapy",
".",
"Women",
"were",
"randomized",
"to",
"treatment",
"(",
"prophylactic",
"levonorgestrel",
"-",
"releasing",
"intrauterine",
"system",
"insertion",
"before",
"the",
"commencement",
"of",
"tamoxifen",
")",
"or",
"control",
"group",
".",
"The",
"uterine",
"cavity",
"was",
"examined",
"by",
"hysteroscopy",
"and",
"endometrial",
"sampling",
"before",
"the",
"commencement",
"of",
"tamoxifen",
"and",
"at",
"12",
",",
"24",
",",
"45",
",",
"and",
"60",
"months",
"afterward",
".",
"Any",
"endometrial",
"polyps",
"or",
"submucosal",
"fibroids",
"were",
"resected",
"through",
"hysteroscopy",
"at",
"each",
"assessment",
"and",
"specimens",
"were",
"sent",
"for",
"histologic",
"confirmation",
".",
"A",
"total",
"of",
"94",
"women",
"completed",
"5",
"-year",
"follow",
"-",
"up",
".",
"There",
"was",
"no",
"significant",
"difference",
"in",
"the",
"occurrence",
"of",
"submucosal",
"fibroids",
"(",
"1",
"[",
"1.8",
"%",
"]",
"compared",
"with",
"2",
"[",
"3.4",
"%",
"]",
")",
"and",
"endometrial",
"hyperplasia",
"(",
"both",
"0",
")",
"in",
"the",
"treatment",
"and",
"control",
"groups",
",",
"respectively",
".",
"Levonorgestrel",
"-",
"releasing",
"intrauterine",
"system",
"significantly",
"reduced",
"de",
"novo",
"endometrial",
"polyps",
"(",
"hazard",
"ratio",
"0.19",
",",
"95",
"%",
"confidence",
"interval",
"0.07",
"-",
"0.48",
")",
"over",
"the",
"course",
"of",
"5",
"years",
"on",
"an",
"intention",
"-",
"to",
"-",
"treat",
"basis",
".",
"There",
"was",
"no",
"statistically",
"significant",
"increase",
"in",
"breast",
"cancer",
"recurrence",
"rate",
"(",
"10",
"[",
"17.2",
"%",
"]",
"compared",
"with",
"6",
"[",
"10.0",
"%",
"]",
")",
"or",
"cancer",
"-",
"related",
"deaths",
"(",
"6",
"[",
"10.3",
"%",
"]",
"compared",
"with",
"5",
"[",
"8.3",
"%",
"]",
")",
"in",
"the",
"treatment",
"group",
",",
"but",
"the",
"study",
"was",
"underpowered",
"in",
"this",
"regard",
".",
"Prophylactic",
"levonorgestrel",
"-",
"releasing",
"intrauterine",
"system",
"prevents",
"de",
"novo",
"endometrial",
"polyps",
"in",
"women",
"using",
"tamoxifen",
".",
"However",
",",
"its",
"role",
"in",
"the",
"prevention",
"of",
"endometrial",
"hyperplasia",
"and",
"adenocarcinoma",
"as",
"well",
"as",
"its",
"effect",
"on",
"risk",
"of",
"breast",
"cancer",
"recurrence",
"remain",
"uncertain",
".",
"Chinese",
"Clinical",
"Trial",
"Registry",
",",
"http://www.chictr.org/en/",
",",
"ChiCTR",
"-",
"TRC-",
"09000625",
".",
"I",
"."
] | [
0,
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
11,
0,
0,
0,
0,
0,
0,
0,
11,
12,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
25,
0,
29,
30,
0,
0,
0,
27,
0,
31,
32,
0,
0,
0,
21,
22,
0,
0,
25,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
27,
0,
31,
32,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
21,
22,
22,
22,
0,
27,
0,
31,
32,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
3 | [
"Preoperative",
"MRI",
"and",
"surgical",
"management",
"in",
"patients",
"with",
"nonpalpable",
"breast",
"cancer",
":",
"the",
"MONET",
"-",
"randomised",
"controlled",
"trial",
".",
"We",
"evaluated",
"whether",
"performing",
"contrast",
"-",
"enhanced",
"breast",
"MRI",
"in",
"addition",
"to",
"mammography",
"and/or",
"ultrasound",
"in",
"patients",
"with",
"nonpalpable",
"suspicious",
"breast",
"lesions",
"improves",
"breast",
"cancer",
"management",
".",
"The",
"MONET",
"-",
"study",
"(",
"MR",
"mammography",
"of",
"nonpalpable",
"breast",
"tumours",
")",
"is",
"a",
"randomised",
"controlled",
"trial",
"in",
"patients",
"with",
"a",
"nonpalpable",
"BIRADS",
"3",
"-",
"5",
"lesion",
".",
"Patients",
"were",
"randomly",
"assigned",
"to",
"receive",
"routine",
"medical",
"care",
",",
"including",
"mammography",
",",
"ultrasound",
"and",
"lesion",
"sampling",
"by",
"large",
"core",
"needle",
"biopsy",
"or",
"additional",
"MRI",
"preceding",
"biopsy",
".",
"Patients",
"with",
"cancer",
"were",
"referred",
"for",
"surgery",
".",
"Primary",
"end",
"-",
"point",
"was",
"the",
"rate",
"of",
"additional",
"surgical",
"procedures",
"(",
"re",
"-",
"excisions",
"and",
"conversion",
"to",
"mastectomy",
")",
"in",
"patients",
"with",
"a",
"nonpalpable",
"breast",
"cancer",
".",
"Four",
"hundred",
"and",
"eighteen",
"patients",
"were",
"randomised",
",",
"207",
"patients",
"were",
"allocated",
"to",
"MRI",
",",
"and",
"211",
"patients",
"to",
"the",
"control",
"group",
".",
"In",
"the",
"MRI",
"group",
"74",
"patients",
"had",
"83",
"malignant",
"lesions",
",",
"compared",
"to",
"75",
"patients",
"with",
"80",
"malignant",
"lesions",
"in",
"the",
"control",
"group",
".",
"The",
"primary",
"breast",
"conserving",
"surgery",
"(",
"BCS",
")",
"rate",
"was",
"similar",
"in",
"both",
"groups",
";",
"68",
"%",
"in",
"the",
"MRI",
"group",
"versus",
"66",
"%",
"in",
"the",
"control",
"group",
".",
"The",
"number",
"of",
"re",
"-",
"excisions",
"performed",
"because",
"of",
"positive",
"resection",
"margins",
"after",
"primary",
"BCS",
"was",
"increased",
"in",
"the",
"MRI",
"group",
";",
"18",
"/",
"53",
"(",
"34",
"%",
")",
"patients",
"in",
"the",
"MRI",
"group",
"versus",
"6",
"/",
"50",
"(",
"12",
"%",
")",
"in",
"the",
"control",
"group",
"(",
"p=",
"0.008",
")",
".",
"The",
"number",
"of",
"conversions",
"to",
"mastectomy",
"did",
"not",
"differ",
"significantly",
"between",
"groups",
".",
"Overall",
",",
"the",
"rate",
"of",
"an",
"additional",
"surgical",
"intervention",
"(",
"BCS",
"and",
"mastectomy",
"combined",
")",
"after",
"initial",
"breast",
"conserving",
"surgery",
"was",
"24",
"/",
"53",
"(",
"45",
"%",
")",
"in",
"the",
"MRI",
"group",
"versus",
"14",
"/",
"50",
"(",
"28",
"%",
")",
"in",
"the",
"control",
"group",
"(",
"p=",
"0.069",
")",
".",
"Addition",
"of",
"MRI",
"to",
"routine",
"clinical",
"care",
"in",
"patients",
"with",
"nonpalpable",
"breast",
"cancer",
"was",
"paradoxically",
"associated",
"with",
"an",
"increased",
"re",
"-",
"excision",
"rate",
".",
"Breast",
"MRI",
"should",
"not",
"be",
"used",
"routinely",
"for",
"preoperative",
"work",
"-",
"up",
"of",
"patients",
"with",
"nonpalpable",
"breast",
"cancer",
"."
] | [
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
0,
21,
22,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
29,
30,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
4 | [
"Association",
"of",
"tamoxifen",
"use",
"and",
"reduced",
"cardiovascular",
"events",
"among",
"asian",
"females",
"with",
"breast",
"cancer",
".",
"Tamoxifen",
"is",
"used",
"for",
"breast",
"cancer",
"treatment",
"and",
"has",
"been",
"reported",
"to",
"be",
"beneficial",
"for",
"the",
"cardiovascular",
"system",
",",
"but",
"it",
"is",
"unclear",
"whether",
"tamoxifen",
"exhibits",
"a",
"favorable",
"cardiovascular",
"effect",
"in",
"Asian",
"patients",
".",
"From",
"January",
",",
"1998",
"to",
"December",
",",
"2006",
",",
"a",
"breast",
"cancer",
"cohort",
"study",
"was",
"conducted",
"using",
"the",
"Taiwan",
"National",
"Health",
"Insurance",
"database",
".",
"Patients",
"were",
"divided",
"according",
"to",
"whether",
"tamoxifen",
"was",
"used",
".",
"Study",
"endpoints",
"were",
"occurrence",
"of",
"acute",
"myocardial",
"infarction",
"(",
"AMI",
")",
",",
"ischemic",
"or",
"hemorrhagic",
"stroke",
"and",
"total",
"cardiovascular",
"events",
".",
"A",
"total",
"of",
"3",
",",
"690",
"female",
"subjects",
"were",
"enrolled",
"(",
"mean",
"age",
"50.1",
"±",
"11.3",
")",
",",
"2",
",",
"056",
"of",
"whom",
"received",
"tamoxifen",
"and",
"1",
",",
"634",
"did",
"not",
".",
"During",
"a",
"mean",
"follow",
"-",
"up",
"of",
"6.9",
"years",
",",
"the",
"tamoxifen",
"group",
"had",
"a",
"significantly",
"lower",
"incidence",
"of",
"AMI",
"(",
"0.15",
"%",
"vs.",
"0.67",
"%",
",",
"P=",
"0.008",
")",
",",
"ischemic",
"stroke",
"(",
"1.99",
"%",
"vs.",
"3.30",
"%",
",",
"P=",
"0.008",
")",
",",
"hemorrhagic",
"stroke",
"(",
"0.15",
"%",
"vs.",
"0.55",
"%",
",",
"P=",
"0.029",
")",
",",
"and",
"total",
"cardiovascular",
"events",
"(",
"2.24",
"%",
"vs.",
"4.16",
"%",
",",
"P",
"<",
"0.001",
")",
"than",
"the",
"non",
"-",
"exposed",
"group",
".",
"After",
"adjusting",
"for",
"comorbidities",
",",
"tamoxifen",
"was",
"independently",
"associated",
"with",
"a",
"reduced",
"risk",
"of",
"myocardial",
"infarction",
"(",
"hazard",
"ratio",
"[",
"HR",
"]",
"0.22",
";",
"95",
"%",
"confidence",
"interval",
"[",
"CI",
"]",
"0.07",
"-",
"0.70",
",",
"ischemic",
"stroke",
"(",
"HR",
"0.52",
";",
"95",
"%",
"CI",
"0.35",
"-",
"0.78",
")",
",",
"hemorrhagic",
"stroke",
"(",
"HR",
"0.25",
";",
"95",
"%",
"CI",
"0.07",
"-",
"0.92",
")",
",",
"and",
"total",
"cardiovascular",
"events",
"(",
"HR",
"0.54",
";",
"95",
"%",
"CI",
"0.37",
"-",
"0.78",
")",
".",
"In",
"Asian",
"female",
"breast",
"cancer",
"patients",
",",
"tamoxifen",
"use",
"was",
"associated",
"with",
"reduced",
"risks",
"of",
"AMI",
",",
"ischemic",
",",
"hemorrhagic",
"stroke",
"and",
"total",
"cardiovascular",
"events",
"."
] | [
0,
0,
17,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
0,
23,
24,
24,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
0,
0,
3,
4,
4,
0,
0,
0,
0,
0,
5,
6,
6,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
5 | [
"Smartphone",
"-",
"Enabled",
"Health",
"Coaching",
"Intervention",
"(",
"iMOVE",
")",
"to",
"Promote",
"Long",
"-",
"Term",
"Maintenance",
"of",
"Physical",
"Activity",
"in",
"Breast",
"Cancer",
"Survivors",
":",
"Protocol",
"for",
"a",
"Feasibility",
"Pilot",
"Randomized",
"Controlled",
"Trial",
".",
"Although",
"physical",
"activity",
"has",
"been",
"shown",
"to",
"contribute",
"to",
"long",
"-",
"term",
"disease",
"control",
"and",
"health",
"in",
"breast",
"cancer",
"survivors",
",",
"a",
"majority",
"of",
"breast",
"cancer",
"survivors",
"do",
"not",
"meet",
"physical",
"activity",
"guidelines",
".",
"Past",
"research",
"has",
"focused",
"on",
"promoting",
"physical",
"activity",
"components",
"for",
"short",
"-",
"term",
"breast",
"cancer",
"survivor",
"benefits",
",",
"but",
"insufficient",
"attention",
"has",
"been",
"devoted",
"to",
"long",
"-",
"term",
"outcomes",
"and",
"sustained",
"exercise",
"adherence",
".",
"We",
"are",
"assessing",
"a",
"health",
"coach",
"intervention",
"(",
"iMOVE",
")",
"that",
"uses",
"mobile",
"technology",
"to",
"increase",
"and",
"sustain",
"physical",
"activity",
"maintenance",
"in",
"initially",
"inactive",
"breast",
"cancer",
"survivors",
".",
"This",
"pilot",
"randomized",
"controlled",
"trial",
"(",
"RCT",
")",
"is",
"an",
"initial",
"step",
"in",
"evaluating",
"the",
"iMOVE",
"intervention",
"and",
"will",
"inform",
"development",
"of",
"a",
"full",
"-",
"scale",
"pragmatic",
"RCT",
".",
"We",
"will",
"enroll",
"107",
"physically",
"inactive",
"breast",
"cancer",
"survivors",
"and",
"randomly",
"assign",
"them",
"to",
"intervention",
"or",
"control",
"groups",
"at",
"the",
"University",
"Health",
"Network",
",",
"a",
"tertiary",
"cancer",
"care",
"center",
"in",
"Toronto",
",",
"Canada",
".",
"Participants",
"will",
"be",
"women",
"(",
"age",
"18",
"to",
"74",
"years",
")",
"stratified",
"by",
"age",
"(",
"55",
"years",
"and",
"older",
"/",
"younger",
"than",
"55",
"years",
")",
"and",
"adjuvant",
"hormone",
"therapy",
"(",
"AHT",
")",
"exposure",
"(",
"AHT",
"vs",
"no",
"AHT",
")",
"following",
"breast",
"cancer",
"treatment",
"with",
"no",
"metastases",
"or",
"recurrence",
"who",
"report",
"less",
"than",
"60",
"minutes",
"of",
"preplanned",
"physical",
"activity",
"per",
"week",
".",
"Both",
"intervention",
"and",
"control",
"groups",
"receive",
"the",
"12",
"-week",
"physical",
"activity",
"program",
"with",
"weekly",
"group",
"sessions",
"and",
"an",
"individualized",
",",
"progressive",
",",
"home",
"-",
"based",
"exercise",
"program",
".",
"The",
"intervention",
"group",
"will",
"additionally",
"receive",
"(",
"1",
")",
"10",
"telephone",
"-",
"based",
"health",
"coaching",
"sessions",
",",
"(",
"2",
")",
"smartphone",
"with",
"data",
"plan",
",",
"if",
"needed",
",",
"(",
"3",
")",
"supportive",
"health",
"tracking",
"software",
"(",
"Connected",
"Wellness",
",",
"NexJ",
"Health",
"Inc",
")",
",",
"and",
"(",
"4",
")",
"a",
"wearable",
"step",
"-",
"counting",
"device",
"linked",
"to",
"a",
"smartphone",
"program",
".",
"We",
"will",
"be",
"assessing",
"recruitment",
"rates",
";",
"acceptability",
"reflected",
"in",
"selective",
",",
"semistructured",
"interviews",
";",
"and",
"enrollment",
",",
"retention",
",",
"and",
"adherence",
"quantitative",
"intervention",
"markers",
"as",
"pilot",
"outcome",
"measures",
".",
"The",
"primary",
"clinical",
"outcome",
"will",
"be",
"directly",
"measured",
"peak",
"oxygen",
"consumption",
".",
"Secondary",
"clinical",
"outcomes",
"include",
"health",
"-",
"related",
"quality",
"of",
"life",
"and",
"anthropometric",
"measures",
".",
"All",
"outcome",
"measures",
"are",
"administered",
"at",
"baseline",
",",
"after",
"exercise",
"program",
"(",
"month",
"3",
")",
",",
"and",
"6",
"months",
"after",
"program",
"(",
"month",
"9",
")",
".",
"This",
"pilot",
"RCT",
"will",
"inform",
"full",
"-",
"scale",
"RCT",
"planning",
".",
"We",
"will",
"assess",
"pilot",
"procedures",
"and",
"interventions",
"and",
"collect",
"preliminary",
"effect",
"estimates",
".",
"ClinicalTrials.gov",
"NCT",
"02620735",
";",
"https://clinicaltrials.gov/ct2/show/NCT",
"02620735",
"(",
"Archived",
"by",
"WebCite",
"at",
"https://clinicaltrials.gov/ct2/show/NCT",
"02620735",
")",
"."
] | [
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
16,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
23,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
6 | [
"Long",
"-",
"term",
"prevention",
"of",
"skeletal",
"complications",
"of",
"metastatic",
"breast",
"cancer",
"with",
"pamidronate",
".",
"Protocol",
"19",
"Aredia",
"Breast",
"Cancer",
"Study",
"Group",
".",
"Pamidronate",
",",
"an",
"aminobisphosphonate",
",",
"has",
"been",
"shown",
"to",
"lower",
"the",
"risk",
"of",
"skeletal",
"complications",
"associated",
"with",
"lytic",
"bone",
"lesions",
"for",
"up",
"to",
"1",
"year",
"in",
"women",
"with",
"stage",
"IV",
"breast",
"cancer",
"who",
"received",
"chemotherapy",
".",
"We",
"studied",
"the",
"long",
"-",
"term",
"effectiveness",
"and",
"safety",
"of",
"continued",
"treatment",
"with",
"intravenous",
"pamidronate",
"infusions",
"for",
"up",
"to",
"2",
"years",
".",
"Three",
"hundred",
"eighty",
"-",
"two",
"women",
"with",
"metastatic",
"breast",
"cancer",
"and",
"lytic",
"bone",
"lesions",
"who",
"received",
"chemotherapy",
"were",
"randomly",
"assigned",
"to",
"receive",
"either",
"90",
"mg",
"of",
"pamidronate",
"or",
"placebo",
"intravenously",
"every",
"3",
"to",
"4",
"weeks",
"in",
"this",
"double",
"-",
"blind",
",",
"multicenter",
",",
"parallel",
"-",
"group",
"trial",
".",
"Patients",
"were",
"evaluated",
"monthly",
"for",
"2",
"years",
"for",
"skeletal",
"complications",
",",
"which",
"included",
"pathologic",
"fractures",
",",
"need",
"for",
"radiation",
"or",
"surgery",
"to",
"treat",
"bone",
"complications",
",",
"spinal",
"cord",
"compression",
",",
"and",
"hypercalcemia",
".",
"Bone",
"pain",
",",
"analgesic",
"use",
",",
"bone",
"biochemical",
"markers",
",",
"performance",
"status",
",",
"quality",
"of",
"life",
",",
"radiologic",
"response",
"in",
"bone",
",",
"and",
"survival",
"were",
"also",
"evaluated",
".",
"As",
"in",
"the",
"first",
"year",
"of",
"treatment",
",",
"the",
"proportion",
"of",
"patients",
"with",
"any",
"skeletal",
"complication",
"was",
"significantly",
"less",
"for",
"the",
"pamidronate",
"than",
"the",
"placebo",
"group",
"at",
"15",
",",
"18",
",",
"21",
",",
"and",
"24",
"months",
"(",
"P",
"<",
".",
"001",
")",
".",
"The",
"proportions",
"of",
"patients",
"with",
"any",
"pathologic",
"fracture",
"(",
"i.e.",
",",
"vertebral",
"and",
"nonvertebral",
"fractures",
")",
",",
"need",
"for",
"radiation",
"or",
"surgery",
"to",
"treat",
"bone",
"complications",
",",
"and",
"hypercalcemia",
"were",
"also",
"statistically",
"less",
"for",
"the",
"pamidronate",
"than",
"the",
"placebo",
"group",
".",
"The",
"median",
"time",
"to",
"the",
"first",
"skeletal",
"complication",
"was",
"13.9",
"months",
"in",
"the",
"pamidronate",
"-",
"treated",
"women",
"and",
"7.0",
"months",
"in",
"the",
"placebo",
"group",
"(",
"P",
"<",
".",
"001",
")",
".",
"Long",
"-",
"term",
"treatment",
"did",
"not",
"result",
"in",
"any",
"unexpected",
"adverse",
"events",
".",
"Survival",
"did",
"not",
"differ",
"between",
"the",
"two",
"groups",
".",
"The",
"risk",
"for",
"osteolytic",
"bone",
"lesion",
"complications",
"in",
"metastatic",
"breast",
"cancer",
"was",
"significantly",
"decreased",
"with",
"monthly",
"infusions",
"of",
"90",
"mg",
"of",
"pamidronate",
",",
"and",
"this",
"effect",
"was",
"maintained",
"for",
"at",
"least",
"2",
"years",
".",
"Pamidronate",
"is",
"a",
"useful",
"adjunct",
"to",
"standard",
"chemotherapy",
"in",
"the",
"palliative",
"treatment",
"of",
"metastatic",
"breast",
"cancer",
"."
] | [
0,
0,
0,
0,
0,
13,
14,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
37,
38,
0,
0,
0,
0,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
7 | [
"OlympiAD",
"final",
"overall",
"survival",
"and",
"tolerability",
"results",
":",
"Olaparib",
"versus",
"chemotherapy",
"treatment",
"of",
"physician",
"'s",
"choice",
"in",
"patients",
"with",
"a",
"germline",
"BRCA",
"mutation",
"and",
"HER",
"2",
"-",
"negative",
"metastatic",
"breast",
"cancer",
".",
"In",
"the",
"OlympiAD",
"study",
",",
"olaparib",
"was",
"shown",
"to",
"improve",
"progression",
"-",
"free",
"survival",
"compared",
"with",
"chemotherapy",
"treatment",
"of",
"physician",
"'s",
"choice",
"(",
"TPC",
")",
"in",
"patients",
"with",
"a",
"germline",
"BRCA",
"1",
"and/or",
"BRCA",
"2",
"mutation",
"(",
"BRCAm",
")",
"and",
"human",
"epidermal",
"growth",
"factor",
"receptor",
"2",
"(",
"HER",
"2",
")",
"-negative",
"metastatic",
"breast",
"cancer",
"(",
"mBC",
")",
".",
"We",
"now",
"report",
"the",
"planned",
"final",
"overall",
"survival",
"(",
"OS",
")",
"results",
",",
"and",
"describe",
"the",
"most",
"common",
"adverse",
"events",
"(",
"AEs",
")",
"to",
"better",
"understand",
"olaparib",
"tolerability",
"in",
"this",
"population",
".",
"OlympiAD",
",",
"a",
"Phase",
"III",
",",
"randomized",
",",
"controlled",
",",
"open",
"-",
"label",
"study",
"(",
"NCT",
"02000622",
")",
",",
"enrolled",
"patients",
"with",
"a",
"germline",
"BRCAm",
"and",
"HER",
"2",
"-",
"negative",
"mBC",
"who",
"had",
"received",
"≤",
"2",
"lines",
"of",
"chemotherapy",
"for",
"mBC",
".",
"Patients",
"were",
"randomized",
"to",
"olaparib",
"tablets",
"(",
"300",
"mg",
"bid",
")",
"or",
"predeclared",
"TPC",
"(",
"capecitabine",
",",
"vinorelbine",
",",
"or",
"eribulin",
")",
".",
"OS",
"and",
"safety",
"were",
"secondary",
"end",
"points",
".",
"A",
"total",
"of",
"205",
"patients",
"were",
"randomized",
"to",
"olaparib",
"and",
"97",
"to",
"TPC",
".",
"At",
"64",
"%",
"data",
"maturity",
",",
"median",
"OS",
"was",
"19.3",
"months",
"with",
"olaparib",
"versus",
"17.1",
"months",
"with",
"TPC",
"(",
"HR",
"0.90",
",",
"95",
"%",
"CI",
"0.66",
"-",
"1.23",
";",
"P",
"=",
"0.513",
")",
";",
"median",
"follow",
"-",
"up",
"was",
"25.3",
"and",
"26.3",
"months",
",",
"respectively",
".",
"HR",
"for",
"OS",
"with",
"olaparib",
"versus",
"TPC",
"in",
"prespecified",
"subgroups",
"were",
":",
"prior",
"chemotherapy",
"for",
"mBC",
"[",
"no",
"(",
"first",
"-",
"line",
"setting",
")",
":",
"0.51",
",",
"95",
"%",
"CI",
"0.29",
"-",
"0.90",
";",
"yes",
"(",
"second",
"/",
"third",
"-",
"line",
")",
":",
"1.13",
",",
"0.79",
"-",
"1.64",
"]",
";",
"receptor",
"status",
"(",
"triple",
"negative",
":",
"0.93",
",",
"0.62",
"-",
"1.43",
";",
"hormone",
"receptor",
"positive",
":",
"0.86",
",",
"0.55",
"-",
"1.36",
")",
";",
"prior",
"platinum",
"(",
"yes",
":",
"0.83",
",",
"0.49",
"-",
"1.45",
";",
"no",
":",
"0.91",
",",
"0.64",
"-",
"1.33",
")",
".",
"Adverse",
"events",
"during",
"olaparib",
"treatment",
"were",
"generally",
"low",
"grade",
"and",
"manageable",
"by",
"supportive",
"treatment",
"or",
"dose",
"modification",
".",
"There",
"was",
"a",
"low",
"rate",
"of",
"treatment",
"discontinuation",
"(",
"4.9",
"%",
")",
",",
"and",
"the",
"risk",
"of",
"developing",
"anemia",
"did",
"not",
"increase",
"with",
"extended",
"olaparib",
"exposure",
".",
"While",
"there",
"was",
"no",
"statistically",
"significant",
"improvement",
"in",
"OS",
"with",
"olaparib",
"compared",
"to",
"TPC",
",",
"there",
"was",
"the",
"possibility",
"of",
"meaningful",
"OS",
"benefit",
"among",
"patients",
"who",
"had",
"not",
"received",
"chemotherapy",
"for",
"metastatic",
"disease",
".",
"Olaparib",
"was",
"generally",
"well",
"-",
"tolerated",
",",
"with",
"no",
"evidence",
"of",
"cumulative",
"toxicity",
"during",
"extended",
"exposure",
".",
"Please",
"see",
"the",
"article",
"online",
"for",
"additional",
"video",
"content",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
37,
38,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
8 | [
"Yoga",
"and",
"self",
"-",
"reported",
"cognitive",
"problems",
"in",
"breast",
"cancer",
"survivors",
":",
"a",
"randomized",
"controlled",
"trial",
".",
"Cancer",
"survivors",
"often",
"report",
"cognitive",
"problems",
".",
"Furthermore",
",",
"decreases",
"in",
"physical",
"activity",
"typically",
"occur",
"over",
"the",
"course",
"of",
"cancer",
"treatment",
".",
"Although",
"physical",
"activity",
"benefits",
"cognitive",
"function",
"in",
"noncancer",
"populations",
",",
"evidence",
"linking",
"physical",
"activity",
"to",
"cognitive",
"function",
"in",
"cancer",
"survivors",
"is",
"limited",
".",
"In",
"our",
"recent",
"randomized",
"controlled",
"trial",
",",
"breast",
"cancer",
"survivors",
"who",
"received",
"a",
"yoga",
"intervention",
"had",
"lower",
"fatigue",
"and",
"inflammation",
"following",
"the",
"trial",
"compared",
"with",
"a",
"wait",
"list",
"control",
"group",
".",
"This",
"secondary",
"analysis",
"of",
"the",
"parent",
"trial",
"addressed",
"yoga",
"'s",
"impact",
"on",
"cognitive",
"complaints",
".",
"Posttreatment",
"stage",
"0",
"-IIIA",
"breast",
"cancer",
"survivors",
"(",
"n",
"=",
"200",
")",
"were",
"randomized",
"to",
"a",
"12",
"-week",
",",
"twice",
"-",
"weekly",
"Hatha",
"yoga",
"intervention",
"or",
"a",
"wait",
"list",
"control",
"group",
".",
"Participants",
"reported",
"cognitive",
"complaints",
"using",
"the",
"Breast",
"Cancer",
"Prevention",
"Trial",
"Cognitive",
"Problems",
"Scale",
"at",
"baseline",
",",
"immediately",
"postintervention",
",",
"and",
"3",
"-month",
"follow",
"-",
"up",
".",
"Cognitive",
"complaints",
"did",
"not",
"differ",
"significantly",
"between",
"groups",
"immediately",
"postintervention",
"(",
"p",
"=",
"0.250",
")",
".",
"However",
",",
"at",
"3",
"-month",
"follow",
"-",
"up",
",",
"yoga",
"participants",
"'",
"Breast",
"Cancer",
"Prevention",
"Trial",
"Cognitive",
"Problems",
"Scale",
"scores",
"were",
"an",
"average",
"of",
"23",
"%",
"lower",
"than",
"wait",
"list",
"participants",
"'",
"scores",
"(",
"p",
"=",
"0.003",
")",
".",
"These",
"group",
"differences",
"in",
"cognitive",
"complaints",
"remained",
"after",
"controlling",
"for",
"psychological",
"distress",
",",
"fatigue",
",",
"and",
"sleep",
"quality",
".",
"Consistent",
"with",
"the",
"primary",
"results",
",",
"those",
"who",
"practiced",
"yoga",
"more",
"frequently",
"reported",
"significantly",
"fewer",
"cognitive",
"problems",
"at",
"3",
"-month",
"follow",
"-",
"up",
"than",
"those",
"who",
"practiced",
"less",
"frequently",
"(",
"p",
"<",
"0.001",
")",
".",
"These",
"findings",
"suggest",
"that",
"yoga",
"can",
"effectively",
"reduce",
"breast",
"cancer",
"survivors",
"'",
"cognitive",
"complaints",
"and",
"prompt",
"further",
"research",
"on",
"mind",
"-",
"body",
"and",
"physical",
"activity",
"interventions",
"for",
"improving",
"cancer",
"-",
"related",
"cognitive",
"problems",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
9 | [
"Risk",
"Model",
"-",
"Guided",
"Antiemetic",
"Prophylaxis",
"vs",
"Physician",
"'s",
"Choice",
"in",
"Patients",
"Receiving",
"Chemotherapy",
"for",
"Early",
"-",
"Stage",
"Breast",
"Cancer",
":",
"A",
"Randomized",
"Clinical",
"Trial",
".",
"Despite",
"multiple",
"patient",
"-",
"centered",
"factors",
"being",
"associated",
"with",
"the",
"risk",
"of",
"chemotherapy",
"-",
"induced",
"nausea",
"and",
"vomiting",
"(",
"CINV",
")",
",",
"these",
"factors",
"are",
"rarely",
"considered",
"when",
"making",
"antiemetic",
"recommendations",
".",
"To",
"compare",
"risk",
"model",
"-",
"guided",
"(",
"RMG",
")",
"antiemetic",
"prophylaxis",
"with",
"physician",
"'s",
"choice",
"(",
"PC",
")",
"in",
"patients",
"receiving",
"chemotherapy",
"for",
"early",
"-",
"stage",
"breast",
"cancer",
".",
"A",
"randomized",
"clinical",
"trial",
"of",
"324",
"patients",
"with",
"early",
"-",
"stage",
"breast",
"cancer",
"undergoing",
"chemotherapy",
"(",
"cyclophosphamide",
"and",
"an",
"anthracycline",
")",
"for",
"the",
"first",
"time",
"at",
"2",
"specialty",
"cancer",
"care",
"centers",
"in",
"Ottawa",
"from",
"April",
"10",
",",
"2012",
",",
"to",
"September",
"2",
",",
"2014",
".",
"Patients",
"were",
"randomized",
"to",
"either",
"the",
"RMG",
"arm",
"(",
"n",
"=",
"154",
")",
"or",
"the",
"PC",
"control",
"arm",
"(",
"n",
"=",
"170",
")",
".",
"Prior",
"to",
"each",
"cycle",
"of",
"chemotherapy",
"patients",
"in",
"the",
"RMG",
"group",
"were",
"categorized",
"as",
"low",
"or",
"high",
"risk",
"for",
"CINV",
",",
"and",
"their",
"antiemetic",
"treatments",
"were",
"adjusted",
"accordingly",
".",
"Patients",
"considered",
"to",
"be",
"at",
"low",
"risk",
"received",
"standard",
"dexamethasone",
"and",
"a",
"5",
"-HT",
"3",
"antagonist",
",",
"while",
"those",
"at",
"high",
"risk",
"also",
"received",
"aprepitant",
"with",
"or",
"without",
"olanzapine",
",",
"based",
"on",
"their",
"risk",
"level",
".",
"The",
"PC",
"control",
"group",
"received",
"antiemetic",
"agents",
"according",
"to",
"the",
"treating",
"physician",
"'s",
"discretion",
".",
"The",
"primary",
"end",
"points",
"were",
"control",
"of",
"both",
"nausea",
"and",
"vomiting",
"in",
"the",
"acute",
"posttreatment",
"period",
"(",
"first",
"24",
"hours",
"after",
"therapy",
")",
"and",
"in",
"the",
"delayed",
"posttreatment",
"period",
"(",
"days",
"2",
"-",
"5",
"after",
"therapy",
")",
".",
"The",
"total",
"numbers",
"of",
"chemotherapy",
"cycles",
"delivered",
"in",
"the",
"RMG",
"and",
"PC",
"control",
"groups",
"were",
"497",
"and",
"551",
"respectively",
".",
"In",
"the",
"acute",
"period",
",",
"significantly",
"more",
"patients",
"in",
"the",
"RMG",
"group",
"reported",
"no",
"nausea",
"(",
"53.7",
"%",
"[",
"95",
"%",
"CI",
",",
"49.2",
"%",
"-",
"58.1",
"%",
"]",
"vs",
"41.6",
"%",
"[",
"95",
"%",
"CI",
",",
"37.4",
"%",
"-",
"45.3",
"%",
"]",
";",
"P",
"<",
".",
"001",
")",
"and",
"no",
"vomiting",
"(",
"91.8",
"%",
"[",
"95",
"%",
"CI",
",",
"89.0",
"%",
"-",
"94.0",
"%",
"]",
"vs",
"82.2",
"%",
"[",
"95",
"%",
"CI",
",",
"78.8",
"%",
"-",
"85.3",
"%",
"]",
";",
"P",
"<",
".",
"001",
")",
"compared",
"with",
"the",
"PC",
"control",
"group",
".",
"Similarly",
",",
"significantly",
"more",
"patients",
"in",
"the",
"RMG",
"group",
"reported",
"no",
"nausea",
"(",
"39.6",
"%",
"[",
"95",
"%",
"CI",
",",
"35.3",
"%",
"-",
"44.1",
"%",
"]",
"vs",
"30.7",
"%",
"[",
"95",
"%",
"CI",
",",
"26.8",
"%",
"-",
"34.7",
"%",
"]",
";",
"P",
"=",
".",
"01",
")",
"and",
"no",
"vomiting",
"(",
"87.1",
"%",
"[",
"95",
"%",
"CI",
",",
"83.8",
"%",
"-",
"90.0",
"%",
")",
"vs",
"78.0",
"%",
"[",
"95",
"%",
"CI",
",",
"74.3",
"%",
"-",
"81.4",
"%",
"]",
";",
"P",
"<",
".",
"001",
")",
"in",
"the",
"delayed",
"period",
"respectively",
".",
"In",
"this",
"trial",
",",
"the",
"RMG",
"antiemetic",
"prophylaxis",
"led",
"to",
"improved",
"control",
"of",
"acute",
"and",
"delayed",
"CINV",
"compared",
"with",
"physician",
"'s",
"choice",
"of",
"therapy",
".",
"clinicaltrials.gov",
"Identifier",
":",
"NCT",
"01913990",
"."
] | [
17,
18,
18,
18,
18,
18,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
10 | [
"No",
"Evidence",
"for",
"Effect",
"of",
"Exercise",
"on",
"Transcriptome",
"of",
"NK",
"Cells",
"in",
"Breast",
"Cancer",
"Patients",
"Undergoing",
"Adjuvant",
"Therapy",
":",
"Results",
"From",
"a",
"Pilot",
"Study",
".",
"Mobilization",
"and",
"activation",
"of",
"natural",
"killer",
"cells",
"(",
"NK",
"cells",
")",
"have",
"been",
"hypothesized",
"to",
"contribute",
"to",
"observed",
"protective",
"effects",
"of",
"exercise",
"on",
"cancer",
"development",
"and",
"progression",
".",
"Some",
"evidence",
"exists",
"for",
"acute",
"effects",
"of",
"aerobic",
"exercise",
"on",
"NK",
"cell",
"mobilization",
"and",
"function",
",",
"i.e.",
",",
"alteration",
"of",
"the",
"gene",
"expression",
"profile",
"of",
"NK",
"cells",
".",
"Yet",
",",
"the",
"chronic",
"effects",
"of",
"exercise",
"training",
",",
"and",
"effects",
"of",
"other",
"modalities",
"than",
"endurance",
"exercise",
"are",
"still",
"understudied",
".",
"Here",
",",
"we",
"investigated",
"the",
"chronic",
"effects",
"of",
"a",
"12",
"-week",
"resistance",
"exercise",
"program",
"on",
"NK",
"cell",
"gene",
"expression",
"in",
"breast",
"cancer",
"patients",
"undergoing",
"adjuvant",
"chemo-",
"or",
"radiotherapy",
".",
"Breast",
"cancer",
"patients",
"were",
"randomly",
"assigned",
"to",
"either",
"a",
"12",
"-week",
"resistance",
"exercise",
"program",
"or",
"a",
"relaxation",
"control",
"group",
"concomitant",
"to",
"adjuvant",
"therapy",
".",
"In",
"a",
"subsample",
"of",
"19",
"participants",
",",
"RNA",
"was",
"extracted",
"from",
"magnet",
"bead",
"isolated",
"NK",
"cells",
"and",
"subsequently",
"analyzed",
"for",
"differential",
"gene",
"expression",
"using",
"microarray",
"Illumina",
"HumanHT-",
"12",
"v",
"4",
"before",
"and",
"after",
"the",
"intervention",
".",
"After",
"chronic",
"exercise",
"intervention",
"several",
"genes",
"showed",
"higher",
"differential",
"expression",
"compared",
"to",
"the",
"control",
"group",
".",
"However",
",",
"after",
"correction",
"for",
"multiple",
"testing",
",",
"baseline",
"-",
"adjusted",
"analyses",
"of",
"covariance",
"indicated",
"no",
"significant",
"differences",
"between",
"the",
"intervention",
"and",
"the",
"control",
"group",
"with",
"regard",
"to",
"the",
"gene",
"expression",
"profile",
".",
"Our",
"findings",
"suggest",
"that",
"12",
"-week",
"resistance",
"-",
"exercise",
"did",
"not",
"alter",
"the",
"gene",
"expression",
"profile",
"of",
"NK",
"cells",
"in",
"breast",
"cancer",
"patients",
"undergoing",
"adjuvant",
"therapy",
"on",
"the",
"long",
"term",
".",
"Further",
"studies",
"with",
"larger",
"sample",
"sizes",
"and",
"specifically",
"designed",
"to",
"investigate",
"whether",
"exercise",
"-",
"induced",
"changes",
"in",
"NK",
"cell",
"function",
"are",
"attributed",
"to",
"acute",
"effects",
"are",
"warranted",
"."
] | [
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
11 | [
"Explicit",
"prognostic",
"disclosure",
"to",
"Asian",
"women",
"with",
"breast",
"cancer",
":",
"A",
"randomized",
",",
"scripted",
"video",
"-",
"vignette",
"study",
"(",
"J",
"-",
"SUPPORT",
"1601",
")",
".",
"Nondisclosure",
"of",
"a",
"poor",
"prognosis",
"to",
"patients",
"with",
"advanced",
"cancer",
"remains",
"a",
"typical",
"practice",
"in",
"Asia",
".",
"Although",
"the",
"importance",
"of",
"prognostic",
"communication",
"has",
"increasingly",
"been",
"recognized",
"worldwide",
",",
"little",
"is",
"known",
"about",
"whether",
"explicit",
"prognostic",
"disclosure",
"positively",
"affects",
"Asian",
"patients",
"with",
"advanced",
"cancer",
".",
"The",
"objective",
"of",
"this",
"study",
"was",
"to",
"examine",
"the",
"effects",
"of",
"explicit",
"prognostic",
"communication",
"on",
"patients",
"with",
"cancer",
"recurrence",
".",
"In",
"this",
"randomized",
",",
"video",
"-",
"vignette",
"study",
",",
"Japanese",
"women",
"with",
"breast",
"cancer",
"who",
"had",
"undergone",
"curative",
"surgery",
"viewed",
"videos",
"of",
"prognostic",
"communication",
"between",
"a",
"patient",
"with",
"recurrent",
",",
"incurable",
"breast",
"cancer",
"and",
"her",
"oncologist",
".",
"The",
"videos",
"differed",
"only",
"in",
"the",
"presence",
"or",
"absence",
"of",
"explicit",
"prognostic",
"disclosure",
".",
"The",
"primary",
"outcome",
"was",
"participants",
"'",
"uncertainty",
"(",
"rated",
"from",
"0",
"to",
"10",
")",
",",
"and",
"the",
"secondary",
"outcomes",
"included",
"anxiety",
"(",
"measured",
"on",
"the",
"State",
"-",
"Trait",
"Anxiety",
"Inventory",
"-",
"State",
":",
"range",
",",
"20",
"-",
"80",
")",
",",
"satisfaction",
"(",
"Patient",
"Satisfaction",
"Questionnaire",
";",
"range",
"0",
"-",
"10",
")",
",",
"self",
"-",
"efficacy",
"(",
"range",
",",
"0",
"-",
"10",
")",
",",
"and",
"willingness",
"to",
"discuss",
"advance",
"care",
"planning",
"(",
"range",
",",
"1",
"-",
"4",
")",
".",
"In",
"total",
",",
"105",
"women",
"participated",
"(",
"mean",
"±",
"SD",
"age",
",",
"53.8",
"±",
"8.2",
"years",
")",
".",
"After",
"viewing",
"the",
"video",
"with",
"more",
"versus",
"less",
"explicit",
"disclosure",
",",
"participants",
"showed",
"significantly",
"lower",
"uncertainty",
"(",
"mean",
"±",
"SE",
"scores",
",",
"5.3",
"±",
"0.2",
"vs",
"5.7",
"±",
"0.2",
",",
"respectively",
";",
"P",
"=",
".",
"032",
")",
"and",
"higher",
"satisfaction",
"(",
"5.6",
"±",
"0.2",
"vs",
"5.2",
"±",
"0.2",
",",
"respectively",
";",
"P",
"=",
".",
"010",
")",
"without",
"increasing",
"anxiety",
"(",
"changes",
"in",
"scores",
"on",
"the",
"State",
"-",
"Trait",
"Anxiety",
"Inventory",
"-",
"State",
":",
"0.06",
"±",
"0.5",
"vs",
"0.6",
"±",
"0.5",
",",
"respectively",
";",
"P",
"=",
".",
"198",
")",
".",
"No",
"significant",
"differences",
"were",
"observed",
"in",
"self",
"-",
"efficacy",
"(",
"5.2",
"±",
"0.2",
"vs",
"5.0",
"±",
"0.2",
",",
"respectively",
";",
"P",
"=",
".",
"277",
")",
"or",
"willingness",
"to",
"discuss",
"advance",
"care",
"planning",
"(",
"2.7",
"±",
"0.1",
"vs",
"2.7",
"±",
"0.1",
",",
"respectively",
";",
"P",
"=",
".",
"240",
")",
".",
"Explicit",
"prognostic",
"disclosure",
"prompted",
"better",
"outcomes",
"than",
"nondisclosure",
"in",
"Japanese",
"women",
"with",
"breast",
"cancer",
".",
"When",
"asked",
"about",
"the",
"prognosis",
"by",
"Asian",
"patients",
"with",
"cancer",
",",
"clinicians",
"may",
"be",
"encouraged",
"to",
"respect",
"their",
"wishes",
"and",
"explicitly",
"discuss",
"the",
"prognosis",
"if",
"deemed",
"appropriate",
"."
] | [
17,
18,
18,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
9,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
12 | [
"Incidence",
"of",
"invasive",
"breast",
"cancer",
"in",
"postmenopausal",
"women",
"after",
"discontinuation",
"of",
"long",
"-",
"term",
"raloxifene",
"administration",
".",
"Postmenopausal",
"women",
"with",
"osteoporosis",
"had",
"a",
"66",
"%",
"relative",
"risk",
"reduction",
"for",
"invasive",
"breast",
"cancer",
"over",
"8",
"years",
"of",
"raloxifene",
"therapy",
"in",
"the",
"randomized",
",",
"placebo",
"-",
"controlled",
"4",
"-year",
"MORE",
"(",
"Multiple",
"Outcomes",
"of",
"Raloxifene",
"Evaluation",
")",
"trial",
"and",
"the",
"CORE",
"(",
"Continuing",
"Outcomes",
"Relevant",
"to",
"Evista",
")",
"trial",
",",
"a",
"4",
"-year",
"follow",
"-",
"up",
"to",
"MORE",
".",
"The",
"first",
"post",
"hoc",
"analysis",
"examined",
"the",
"effects",
"of",
"raloxifene",
"on",
"the",
"cumulative",
"incidence",
"of",
"invasive",
"breast",
"cancer",
"on",
"a",
"yearly",
"basis",
".",
"Another",
"analysis",
"compared",
"the",
"incidence",
"of",
"invasive",
"breast",
"cancer",
"in",
"3967",
"patients",
"who",
"continued",
"raloxifene",
"for",
"8",
"years",
"(",
"RLX",
"-",
"C",
",",
"n",
"=",
"2280",
")",
",",
"discontinued",
"raloxifene",
"after",
"4",
"years",
"in",
"MORE",
"(",
"RLX",
"-",
"D",
",",
"n",
"=",
"401",
")",
",",
"or",
"took",
"placebo",
"(",
"n",
"=",
"1286",
")",
"for",
"a",
"mean",
"2.9",
"years",
"'",
"treatment",
"duration",
"(",
"57",
",",
"338",
"patient",
"-",
"years",
")",
".",
"The",
"unadjusted",
"breast",
"cancer",
"incidence",
"rate",
"was",
"5.39",
"per",
"1000",
"patient",
"-",
"years",
"in",
"the",
"placebo",
"group",
"compared",
"with",
"2.26",
"in",
"the",
"RLX",
"-",
"C",
"group",
"(",
"hazard",
"ratio",
"[",
"HR",
"]",
",",
"0.41",
"[",
"95",
"%",
"CI",
"0.21",
"-",
"0.81",
"]",
")",
"and",
"3.59",
"in",
"the",
"RLX",
"-",
"D",
"group",
"(",
"HR",
",",
"0.69",
"[",
"95",
"%",
"CI",
"0.23",
"-",
"2.01",
"]",
")",
".",
"Because",
"the",
"choice",
"of",
"taking",
"the",
"study",
"drug",
"was",
"not",
"randomized",
"in",
"CORE",
",",
"propensity",
"scores",
"were",
"used",
"to",
"adjust",
"for",
"potential",
"imbalances",
"in",
"baseline",
"characteristics",
"before",
"CORE",
".",
"Results",
"after",
"adjustment",
"by",
"the",
"propensity",
"score",
"method",
"were",
"similar",
"to",
"the",
"unadjusted",
"results",
".",
"This",
"analysis",
"suggests",
"a",
"persistent",
"effect",
"for",
"breast",
"cancer",
"risk",
"reduction",
"in",
"patients",
"who",
"discontinued",
"raloxifene",
",",
"although",
"this",
"conclusion",
"is",
"limited",
"by",
"the",
"small",
"sample",
"size",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
19,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
13 | [
"Impact",
"of",
"a",
"higher",
"radiation",
"dose",
"on",
"local",
"control",
"and",
"survival",
"in",
"breast",
"-",
"conserving",
"therapy",
"of",
"early",
"breast",
"cancer",
":",
"10",
"-year",
"results",
"of",
"the",
"randomized",
"boost",
"versus",
"no",
"boost",
"EORTC",
"22881",
"-",
"10882",
"trial",
".",
"To",
"investigate",
"the",
"long",
"-",
"term",
"impact",
"of",
"a",
"boost",
"radiation",
"dose",
"of",
"16",
"Gy",
"on",
"local",
"control",
",",
"fibrosis",
",",
"and",
"overall",
"survival",
"for",
"patients",
"with",
"stage",
"I",
"and",
"II",
"breast",
"cancer",
"who",
"underwent",
"breast",
"-",
"conserving",
"therapy",
".",
"A",
"total",
"of",
"5",
",",
"318",
"patients",
"with",
"microscopically",
"complete",
"excision",
"followed",
"by",
"whole",
"-",
"breast",
"irradiation",
"of",
"50",
"Gy",
"were",
"randomly",
"assigned",
"to",
"receive",
"either",
"a",
"boost",
"dose",
"of",
"16",
"Gy",
"(",
"2",
",",
"661",
"patients",
")",
"or",
"no",
"boost",
"dose",
"(",
"2",
",",
"657",
"patients",
")",
",",
"with",
"a",
"median",
"follow",
"-",
"up",
"of",
"10.8",
"years",
".",
"The",
"median",
"age",
"was",
"55",
"years",
".",
"Local",
"recurrence",
"was",
"reported",
"as",
"the",
"first",
"treatment",
"failure",
"in",
"278",
"patients",
"with",
"no",
"boost",
"versus",
"165",
"patients",
"with",
"boost",
";",
"at",
"10",
"years",
",",
"the",
"cumulative",
"incidence",
"of",
"local",
"recurrence",
"was",
"10.2",
"%",
"versus",
"6.2",
"%",
"for",
"the",
"no",
"boost",
"and",
"the",
"boost",
"group",
",",
"respectively",
"(",
"P",
"<",
".",
"0001",
")",
".",
"The",
"hazard",
"ratio",
"of",
"local",
"recurrence",
"was",
"0.59",
"(",
"0.46",
"to",
"0.76",
")",
"in",
"favor",
"of",
"the",
"boost",
",",
"with",
"no",
"statistically",
"significant",
"interaction",
"per",
"age",
"group",
".",
"The",
"absolute",
"risk",
"reduction",
"at",
"10",
"years",
"per",
"age",
"group",
"was",
"the",
"largest",
"in",
"patients",
"<",
"or=",
"40",
"years",
"of",
"age",
":",
"23.9",
"%",
"to",
"13.5",
"%",
"(",
"P",
"=",
".",
"0014",
")",
".",
"As",
"a",
"result",
",",
"the",
"number",
"of",
"salvage",
"mastectomies",
"has",
"been",
"reduced",
"by",
"41",
"%",
".",
"Severe",
"fibrosis",
"was",
"statistically",
"significantly",
"increased",
"(",
"P",
"<",
".",
"0001",
")",
"in",
"the",
"boost",
"group",
",",
"with",
"a",
"10",
"-year",
"rate",
"of",
"4.4",
"%",
"versus",
"1.6",
"%",
"in",
"the",
"no",
"boost",
"group",
"(",
"P",
"<",
".",
"0001",
")",
".",
"Survival",
"at",
"10",
"years",
"was",
"82",
"%",
"in",
"both",
"arms",
".",
"After",
"a",
"median",
"follow",
"-",
"up",
"period",
"of",
"10.8",
"years",
",",
"a",
"boost",
"dose",
"of",
"16",
"Gy",
"led",
"to",
"improved",
"local",
"control",
"in",
"all",
"age",
"groups",
",",
"but",
"no",
"difference",
"in",
"survival",
"."
] | [
0,
0,
0,
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
4,
4,
0,
0,
0,
19,
20,
20,
0,
5,
6,
6,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
21,
22,
0,
0,
21,
22,
22,
22,
22,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
14 | [
"A",
"phase",
"III",
"adjuvant",
"randomised",
"trial",
"of",
"6",
"cycles",
"of",
"5",
"-fluorouracil",
"-",
"epirubicine",
"-",
"cyclophosphamide",
"(",
"FEC",
"100",
")",
"versus",
"4",
"FEC",
"100",
"followed",
"by",
"4",
"Taxol",
"(",
"FEC",
"-",
"T",
")",
"in",
"node",
"positive",
"breast",
"cancer",
"patients",
"(",
"Trial",
"B",
"2000",
")",
".",
"Standard",
"adjuvant",
"chemotherapy",
"regimens",
"for",
"patients",
"with",
"node",
"positive",
"(",
"N+",
")",
"breast",
"cancer",
"consisted",
"of",
"anthracycline",
"followed",
"by",
"taxane",
".",
"The",
"European",
"Association",
"for",
"Research",
"in",
"Oncology",
"embarked",
"in",
"2000",
"on",
"a",
"phase",
"III",
"trial",
"comparing",
"6",
"cycles",
"of",
"FEC",
"100",
"versus",
"4",
"FEC",
"100",
"followed",
"by",
"4",
"Taxol",
".",
"Primary",
"end",
"-",
"point",
"was",
"disease",
"free",
"survival",
".",
"Secondary",
"end",
"-",
"points",
"were",
"overall",
"survival",
",",
"local",
"recurrence",
"free",
"interval",
",",
"metastases",
"free",
"interval",
"and",
"safety",
".",
"Between",
"March",
"2000",
"and",
"December",
"2002",
",",
"837",
"patients",
"were",
"randomised",
"between",
"6",
"FEC",
"100",
"for",
"6",
"cycles",
"(",
"417",
"patients",
")",
"or",
"FEC",
"100",
"for",
"4",
"cycles",
"then",
"Taxol",
"175",
"mg",
"/",
"m",
"(",
"2",
")",
"/",
"3",
"weeks",
"for",
"4",
"cycles",
"(",
"4",
"FEC",
"100",
"-",
"4",
"T",
")",
"(",
"420",
"patients",
")",
".",
"One",
"thousand",
"patients",
"had",
"been",
"planned",
"initially",
"but",
"the",
"trial",
"was",
"closed",
"earlier",
"due",
"to",
"slow",
"accrual",
".",
"Hazard",
"ratios",
"(",
"HRs",
")",
"were",
"0.99",
"for",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
"(",
"95",
"%",
"CI",
":",
"0.77",
"-",
"1.26",
";",
"p=",
"0.91",
")",
",",
"and",
"0.85",
"for",
"overall",
"survival",
"(",
"OS",
")",
"(",
"95",
"%",
"CI",
":",
"0.62",
"-",
"1.15",
";",
"p=",
"0.29",
")",
".",
"Nine",
"-",
"year",
"DFS",
"were",
"62.9",
"%",
"versus",
"62.5",
"%",
"for",
"6",
"FEC",
"100",
"and",
"4",
"FEC",
"100",
"-",
"4",
"T",
",",
"respectively",
".",
"Nine",
"-",
"year",
"OS",
"were",
"73.9",
"%",
"versus",
"77",
"%",
"for",
"6",
"FEC",
"100",
"and",
"4",
"FEC",
"100",
"-",
"4",
"T",
",",
"respectively",
".",
"Toxicity",
"analyses",
"based",
"on",
"803",
"evaluable",
"patients",
"showed",
"that",
"overall",
"grade",
"3",
"-",
"4",
"toxicities",
"were",
"similar",
"in",
"both",
"arms",
"(",
"63",
"%",
"versus",
"58",
"%",
"for",
"6",
"FEC",
"100",
"arm",
"and",
"4",
"FEC",
"100",
"-",
"4",
"T",
"arm",
",",
"respectively",
";",
"p=",
"0.16",
")",
".",
"In",
"this",
"trial",
"replacing",
"the",
"last",
"2",
"FEC",
"100",
"cycles",
"of",
"6",
"FEC",
"100",
"regimen",
"by",
"4",
"Taxol",
"does",
"not",
"lead",
"to",
"a",
"discernable",
"DFS",
"or",
"OS",
"advantage",
".",
"The",
"lack",
"of",
"a",
"significant",
"difference",
"between",
"the",
"randomised",
"treatment",
"arms",
"may",
"however",
"be",
"due",
"to",
"a",
"lack",
"of",
"power",
"of",
"this",
"trial",
"to",
"detect",
"small",
",",
"yet",
"clinically",
"worthwhile",
",",
"treatment",
"benefits",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
0,
19,
20,
20,
20,
20,
20,
20,
20,
20,
20,
20,
20,
0,
9,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
23,
24,
0,
23,
24,
24,
24,
0,
23,
24,
24,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
1,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
15 | [
"Lifestyle",
"and",
"breast",
"cancer",
"recurrences",
":",
"the",
"DIANA-",
"5",
"trial",
".",
"The",
"DIANA",
"(",
"Diet",
"and",
"Androgens",
")",
"-",
"5",
"study",
"is",
"a",
"multi",
"-",
"institutional",
"randomized",
"controlled",
"trial",
"of",
"the",
"effectiveness",
"of",
"a",
"diet",
"based",
"on",
"Mediterranean",
"and",
"macrobiotic",
"recipes",
"and",
"principles",
",",
"associated",
"with",
"moderate",
"physical",
"activity",
",",
"in",
"reducing",
"additional",
"breast",
"cancer",
"events",
"in",
"women",
"with",
"early",
"stage",
"invasive",
"breast",
"cancer",
"at",
"high",
"risk",
"of",
"recurrence",
"because",
"of",
"metabolic",
"or",
"endocrine",
"milieu",
".",
"The",
"intervention",
"is",
"expected",
"to",
"reduce",
"serum",
"insulin",
"and",
"sex",
"hormones",
",",
"which",
"were",
"associated",
"with",
"breast",
"prognosis",
"in",
"previous",
"studies",
".",
"Between",
"2008",
"and",
"2010",
",",
"the",
"study",
"randomly",
"assigned",
"1208",
"patients",
"to",
"an",
"intensive",
"diet",
"and",
"exercise",
"intervention",
"or",
"to",
"a",
"comparison",
"group",
",",
"to",
"be",
"followed",
"-",
"up",
"through",
"2015",
".",
"General",
"lifestyle",
"recommendations",
"for",
"the",
"prevention",
"of",
"cancer",
"are",
"given",
"to",
"both",
"groups",
",",
"and",
"the",
"intervention",
"group",
"is",
"being",
"offered",
"a",
"comprehensive",
"lifestyle",
"intervention",
",",
"including",
"cooking",
"classes",
",",
"conferences",
",",
"common",
"meals",
"and",
"exercise",
"sessions",
".",
"Adherence",
"assessments",
"occurred",
"at",
"baseline",
"and",
"at",
"12",
"months",
"and",
"are",
"planned",
"at",
"36",
"and",
"60",
"months",
".",
"They",
"include",
"food",
"frequency",
"diaries",
",",
"anthropometric",
"measures",
",",
"body",
"fat",
"distribution",
"assessed",
"with",
"impedance",
"scale",
",",
"one",
"week",
"registration",
"of",
"physical",
"activity",
"with",
"a",
"multisensor",
"arm",
"-",
"band",
"monitor",
",",
"metabolic",
"and",
"endocrine",
"blood",
"parameters",
".",
"Outcome",
"breast",
"cancer",
"events",
"are",
"assessed",
"through",
"self",
"report",
"at",
"semi",
"annual",
"meetings",
"or",
"telephone",
"interview",
"and",
"are",
"validated",
"through",
"medical",
"record",
"verification",
".",
"The",
"randomized",
"groups",
"were",
"comparable",
"for",
"age",
"(",
"51.8",
"years",
")",
",",
"proportion",
"of",
"ER",
"-",
"negative",
"tumors",
"(",
"22",
"%",
")",
",",
"axillary",
"node",
"metastasis",
"(",
"42",
"%",
")",
",",
"reproductive",
"variables",
",",
"tobacco",
"smoking",
",",
"blood",
"pressure",
",",
"anthropometric",
"measurements",
"and",
"hormonal",
"and",
"metabolic",
"parameters",
".",
"DIANA-",
"5",
"has",
"the",
"potential",
"to",
"establish",
"whether",
"a",
"Mediterranean",
"-",
"macrobiotic",
"lifestyle",
"may",
"reduce",
"breast",
"cancer",
"recurrences",
".",
"We",
"will",
"assess",
"evidence",
"of",
"effectiveness",
",",
"first",
"by",
"comparing",
"the",
"incidence",
"of",
"additional",
"breast",
"cancer",
"events",
"(",
"local",
"or",
"distant",
"recurrence",
",",
"second",
"ipsilateral",
"or",
"contralateral",
"cancer",
")",
"in",
"the",
"intervention",
"and",
"in",
"the",
"control",
"group",
",",
"by",
"an",
"intention",
"-",
"to",
"-",
"treat",
"analysis",
",",
"and",
"second",
"by",
"analyzing",
"the",
"incidence",
"of",
"breast",
"cancer",
"events",
"in",
"the",
"total",
"study",
"population",
"by",
"compliance",
"assessment",
"score",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
17,
18,
18,
18,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
16 | [
"Group",
"medical",
"consultations",
"(",
"GMCs",
")",
"and",
"tablet",
"-",
"based",
"online",
"support",
"group",
"sessions",
"in",
"the",
"follow",
"-",
"up",
"of",
"breast",
"cancer",
":",
"A",
"multicenter",
"randomized",
"controlled",
"trial",
".",
"Group",
"medical",
"consultations",
"(",
"GMCs",
")",
"provide",
"individual",
"medical",
"visits",
"in",
"the",
"presence",
"of",
"≤",
"7",
"peer",
"-",
"patients",
".",
"In",
"the",
"follow",
"-",
"up",
"of",
"breast",
"cancer",
",",
"we",
"evaluated",
"the",
"efficacy",
"of",
"a",
"new",
"type",
"of",
"blended",
"care",
"My",
"-",
"GMC",
",",
"a",
"GMC",
"combined",
"with",
"a",
"tablet",
"-",
"based",
"online",
"app",
",",
"consisting",
"of",
"three",
"online",
"support",
"group",
"sessions",
"(",
"SGS",
")",
"and",
"additional",
"information",
".",
"This",
"randomized",
"controlled",
"trial",
"compared",
"the",
"effect",
"of",
"My",
"-",
"GMC",
"(",
"n",
"=",
"59",
")",
"with",
"one",
"individual",
"medical",
"visit",
"(",
"n",
"=",
"50",
")",
"(",
"care",
"as",
"usual",
")",
".",
"Between",
"-",
"group",
"differences",
"on",
"the",
"outcomes",
"distress",
"and",
"empowerment",
"were",
"analyzed",
"1",
"week",
",",
"3",
"and",
"6",
"months",
"after",
"the",
"visit",
".",
"No",
"between",
"-",
"group",
"differences",
"were",
"found",
"for",
"the",
"primary",
"outcomes",
"distress",
"and",
"empowerment",
".",
"More",
"themes",
"were",
"discussed",
"in",
"GMCs",
"compared",
"to",
"individual",
"visits",
".",
"Significantly",
"more",
"patients",
"experienced",
"peer",
"-",
"support",
"in",
"GMCs",
"(",
"78",
"%",
")",
"than",
"via",
"the",
"online",
"app",
"(",
"29",
"%",
")",
".",
"Satisfaction",
"with",
"the",
"online",
"app",
"was",
"low",
".",
"My",
"-",
"GMC",
"did",
"not",
"result",
"in",
"improvements",
"in",
"distress",
"or",
"empowerment",
",",
"which",
"might",
"partly",
"be",
"explained",
"by",
"low",
"baseline",
"distress",
"levels",
".",
"This",
"paper",
"provides",
"valuable",
"information",
"concerning",
"factors",
"on",
"organizational",
"level",
"as",
"well",
"as",
"individual",
"level",
"influencing",
"the",
"evaluation",
"of",
"a",
"blended",
"care",
"intervention",
".",
"My",
"-",
"GMC",
"provided",
"an",
"innovative",
"alternative",
",",
"combining",
"professional",
"and",
"peer",
"-",
"support",
"in",
"face",
"-",
"to",
"-",
"face",
"and",
"online",
"SGS",
",",
"resulting",
"in",
"additional",
"information",
"provision",
"and",
"peer",
"-",
"support",
".",
"Further",
"improvement",
"of",
"the",
"apps",
"is",
"needed",
"to",
"improve",
"user",
"satisfaction",
".",
"NTR",
"3771",
"."
] | [
17,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
17 | [
"Survival",
"outcomes",
"of",
"neoadjuvant",
"chemotherapy",
"with",
"zoledronic",
"acid",
"for",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
".",
"A",
"randomized",
"phase",
"2",
"trial",
"in",
"women",
"with",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
"has",
"shown",
"that",
"adding",
"zoledronic",
"acid",
"(",
"ZOL",
")",
"to",
"neoadjuvant",
"chemotherapy",
"(",
"CT",
")",
"has",
"potential",
"anticancer",
"benefits",
"in",
"postmenopausal",
"and",
"triple",
"-",
"negative",
"(",
"TN",
")",
"breast",
"cancer",
"patients",
".",
"We",
"report",
"the",
"data",
"for",
"the",
"secondary",
"end",
"point",
"of",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
".",
"Patients",
"were",
"randomly",
"assigned",
"to",
"receive",
"CT",
"or",
"CT",
"+",
"ZOL",
"(",
"CT",
"-",
"Z",
")",
".",
"All",
"patients",
"received",
"four",
"cycles",
"of",
"FEC",
"100",
"followed",
"by",
"12",
"cycles",
"of",
"paclitaxel",
"weekly",
".",
"ZOL",
"(",
"4",
"mg",
")",
"was",
"administered",
"3",
"-",
"4",
"times",
"weekly",
"for",
"7",
"wk",
"to",
"the",
"CT",
"-",
"Z",
"group",
"patients",
".",
"The",
"primary",
"end",
"point",
"was",
"pathologic",
"complete",
"response",
"(",
"pCR",
")",
".",
"The",
"secondary",
"end",
"points",
"were",
"the",
"clinical",
"response",
"rates",
",",
"rate",
"of",
"breast",
"-",
"conserving",
"surgery",
",",
"safety",
",",
"and",
"DFS",
".",
"Of",
"the",
"188",
"patients",
"enrolled",
",",
"95",
"were",
"assigned",
"to",
"the",
"CT",
"group",
"and",
"93",
"to",
"the",
"CT",
"-",
"Z",
"group",
".",
"DFS",
"and",
"overall",
"survival",
"were",
"analyzed",
"in",
"92",
"and",
"88",
"patients",
"with",
"the",
"mean",
"times",
"of",
"5.15",
"y",
"and",
"5.38",
"y",
",",
"respectively",
".",
"The",
"3",
"-y",
"DFS",
"rate",
"was",
"84.6",
"%",
"in",
"the",
"CT",
"group",
"and",
"90.8",
"%",
"in",
"the",
"CT",
"-",
"Z",
"group",
"(",
"P",
"=",
"0.188",
")",
".",
"The",
"particular",
"benefit",
"from",
"ZOL",
"for",
"the",
"neoadjuvant",
"CT",
"seen",
"as",
"improvement",
"of",
"the",
"pCR",
"rate",
"was",
"indicated",
"in",
"the",
"3",
"-y",
"DFS",
"period",
"for",
"TN",
"cancer",
"cases",
"(",
"CT",
"versus",
"CT",
"-",
"Z",
":",
"70.6",
"%",
"versus",
"94.1",
"%",
")",
"but",
"not",
"for",
"postmenopausal",
"cases",
".",
"ZOL",
"did",
"not",
"improve",
"DFS",
"when",
"combined",
"with",
"CT",
".",
"However",
",",
"the",
"improvement",
"of",
"the",
"pCR",
"rate",
"translated",
"to",
"survival",
"outcomes",
"in",
"TN",
"breast",
"cancer",
".",
"The",
"short",
"-",
"term",
"application",
"of",
"ZOL",
"may",
"not",
"be",
"sufficient",
"to",
"improve",
"the",
"outcome",
"in",
"postmenopausal",
"patients",
"."
] | [
0,
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
23,
24,
24,
24,
24,
24,
0,
23,
0,
0,
23,
0,
0,
0,
1,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
21,
0,
21,
22,
0,
0,
0,
5,
0,
3,
0,
0,
0,
0,
0,
0,
35,
36,
0,
33,
34,
0,
0,
0,
0,
21,
22,
22,
22,
0,
31,
32,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
18 | [
"Ten",
"-",
"year",
"follow",
"-",
"up",
"of",
"a",
"randomized",
"controlled",
"trial",
"of",
"adjuvant",
"clodronate",
"treatment",
"in",
"node",
"-",
"positive",
"breast",
"cancer",
"patients",
".",
"Ten",
"-",
"year",
"follow",
"-",
"up",
"results",
"are",
"presented",
"of",
"an",
"adjuvant",
"clodronate",
"trial",
"in",
"patients",
"with",
"primary",
"breast",
"cancer",
".",
"Between",
"1990",
"and",
"1993",
",",
"299",
"women",
"with",
"primary",
"node",
"positive",
"breast",
"cancer",
"were",
"randomized",
"to",
"oral",
"clodronate",
"1600",
"mg",
"daily",
"(",
"149",
")",
"or",
"controls",
"(",
"150",
")",
"for",
"3",
"years",
".",
"All",
"patients",
"received",
"adjuvant",
"chemo-",
"or",
"endocrine",
"therapy",
".",
"Within",
"10",
"years",
"bone",
"metastases",
"were",
"detected",
"at",
"the",
"same",
"frequency",
"in",
"the",
"clodronate",
"and",
"control",
"groups",
":",
"44",
"(",
"32",
"%",
")",
"vs.",
"42",
"(",
"29",
"%",
")",
",",
"respectively",
",",
"(",
"p=",
"0.35",
")",
".",
"The",
"frequency",
"of",
"non",
"-",
"skeletal",
"recurrences",
"(",
"visceral",
"and",
"local",
")",
"was",
"significantly",
"higher",
"in",
"the",
"clodronate",
"group",
"69",
"(",
"50",
"%",
")",
"as",
"compared",
"with",
"the",
"controls",
"51",
"(",
"36",
"%",
")",
"(",
"p=",
"0.005",
")",
".",
"Ten",
"-",
"year",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
"remained",
"significantly",
"lower",
"in",
"the",
"clodronate",
"group",
"(",
"45",
"%",
"vs.",
"58",
"%",
",",
"p=",
"0.01",
",",
"respectively",
")",
".",
"This",
"was",
"especially",
"seen",
"in",
"oestrogen",
"receptor",
"negative",
"patients",
"(",
"25",
"%",
"vs.",
"58",
"%",
",",
"p=",
"0.004",
",",
"respectively",
")",
".",
"No",
"significant",
"overall",
"survival",
"difference",
"was",
"found",
"between",
"the",
"groups",
".",
"As",
"previously",
"reported",
"3",
"-year",
"adjuvant",
"clodronate",
"treatment",
"did",
"not",
"prevent",
"the",
"development",
"of",
"bone",
"metastases",
"in",
"node",
"-",
"positive",
"breast",
"cancer",
"patients",
".",
"A",
"negative",
"effect",
"of",
"clodronate",
"on",
"DFS",
"by",
"increasing",
"the",
"development",
"of",
"visceral",
"metastases",
"was",
"still",
"seen",
"at",
"10",
"years",
",",
"but",
"this",
"did",
"not",
"significantly",
"compromise",
"overall",
"survival",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
19,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
29,
30,
0,
0,
27,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
27,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
19 | [
"Intake",
"of",
"vitamin",
"D",
"and",
"calcium",
",",
"sun",
"exposure",
",",
"and",
"risk",
"of",
"breast",
"cancer",
"subtypes",
"among",
"black",
"women",
".",
"The",
"randomized",
"placebo",
"-",
"controlled",
"Vitamin",
"D",
"and",
"Omega-",
"3",
"Trial",
"suggested",
"a",
"possible",
"benefit",
"of",
"vitamin",
"D",
"on",
"cancer",
"incidence",
"among",
"black",
"individuals",
".",
"However",
",",
"data",
"are",
"limited",
"regarding",
"the",
"impact",
"of",
"vitamin",
"D",
"on",
"breast",
"cancer",
"subtypes",
"among",
"African",
"-",
"American",
"/",
"black",
"women",
",",
"who",
"tend",
"to",
"develop",
"more",
"aggressive",
"forms",
"of",
"breast",
"cancer",
".",
"We",
"hypothesize",
"that",
"more",
"vitamin",
"D",
"exposure",
"(",
"through",
"diet",
",",
"supplements",
",",
"and",
"sunlight",
")",
"and",
"higher",
"intake",
"of",
"calcium",
"are",
"associated",
"with",
"decreased",
"risk",
"of",
"estrogen",
"receptor",
"(",
"ER",
")",
"+",
"and",
"ER-",
"breast",
"cancer",
",",
"and",
"of",
"triple",
"-",
"negative",
"breast",
"cancer",
"(",
"TNBC",
")",
"among",
"black",
"women",
".",
"This",
"study",
"was",
"conducted",
"among",
"1724",
"black",
"cases",
"and",
"1233",
"controls",
"in",
"the",
"Women",
"'s",
"Circle",
"of",
"Health",
"Study",
"(",
"WCHS",
")",
"and",
"WCHS",
"2",
".",
"Polytomous",
"logistic",
"regressions",
"were",
"used",
"to",
"estimate",
"ORs",
"and",
"95",
"%",
"CIs",
"of",
"ER+",
"and",
"ER-",
"breast",
"cancer",
";",
"logistic",
"regressions",
"were",
"used",
"for",
"TNBC",
".",
"The",
"ORs",
"from",
"each",
"study",
"were",
"pooled",
"using",
"an",
"inverse",
"-",
"variance",
"-",
"weighted",
"random",
"-",
"effects",
"model",
".",
"Dietary",
"vitamin",
"D",
"and",
"calcium",
"intake",
"were",
"not",
"associated",
"with",
"risk",
"of",
"breast",
"cancer",
"subtypes",
"in",
"the",
"pooled",
"analysis",
".",
"For",
"supplemental",
"vitamin",
"D",
",",
"we",
"observed",
"possible",
"inverse",
"associations",
"between",
"intake",
"of",
"≤",
"800",
"IU",
"/",
"d",
"(",
"compared",
"with",
"nonuse",
")",
"and",
"risk",
"of",
"several",
"subtypes",
",",
"with",
"effects",
"that",
"appeared",
"strongest",
"for",
"TNBC",
"(",
"OR",
":",
"0.58",
";",
"95",
"%",
"CI",
":",
"0.35",
",",
"0.94",
")",
";",
"no",
"association",
"was",
"found",
"for",
">",
"800",
"IU",
"/",
"d.",
"More",
"daylight",
"hours",
"spent",
"outdoors",
"in",
"a",
"year",
"was",
"associated",
"with",
"lower",
"risk",
"of",
"ER+",
",",
"ER-",
",",
"and",
"TNBC",
"(",
"e.g.",
",",
"highest",
"compared",
"with",
"lowest",
"quartile",
":",
"TNBC",
"OR",
":",
"0.53",
";",
"95",
"%",
"CI",
":",
"0.31",
",",
"0.91",
";",
"P",
"-",
"trend",
"=",
"0.02",
")",
".",
"Moderate",
"supplemental",
"vitamin",
"D",
"intake",
"was",
"associated",
"with",
"decreased",
"risk",
"of",
"TNBC",
",",
"and",
"increased",
"sun",
"exposure",
"was",
"associated",
"with",
"reduced",
"risk",
"of",
"ER+",
",",
"ER-",
",",
"and",
"TNBC",
"among",
"black",
"women",
"."
] | [
0,
0,
17,
18,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
12,
12,
12,
12,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
5,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
20 | [
"A",
"Randomized",
"Controlled",
"Trial",
"of",
"Green",
"Tea",
"Extract",
"Supplementation",
"and",
"Mammographic",
"Density",
"in",
"Postmenopausal",
"Women",
"at",
"Increased",
"Risk",
"of",
"Breast",
"Cancer",
".",
"Epidemiologic",
"and",
"animal",
"studies",
"suggest",
"a",
"protective",
"role",
"of",
"green",
"tea",
"against",
"breast",
"cancer",
".",
"However",
",",
"the",
"underlying",
"mechanism",
"is",
"not",
"understood",
".",
"We",
"conducted",
"a",
"randomized",
",",
"double",
"-",
"blinded",
",",
"placebo",
"-",
"controlled",
"phase",
"II",
"clinical",
"trial",
"to",
"investigate",
"whether",
"supplementation",
"with",
"green",
"tea",
"extract",
"(",
"GTE",
")",
"modifies",
"mammographic",
"density",
"(",
"MD",
")",
",",
"as",
"a",
"potential",
"mechanism",
",",
"involving",
"1",
",",
"075",
"healthy",
"postmenopausal",
"women",
".",
"Women",
"assigned",
"to",
"the",
"treatment",
"arm",
"consumed",
"daily",
"4",
"decaffeinated",
"GTE",
"capsules",
"containing",
"1",
",",
"315",
"mg",
"total",
"catechins",
",",
"including",
"843",
"mg",
"epigallocatechin-",
"3",
"-",
"gallate",
"(",
"EGCG",
")",
"for",
"12",
"months",
".",
"A",
"computer",
"-",
"assisted",
"method",
"(",
"Madena",
")",
"was",
"used",
"to",
"assess",
"MD",
"in",
"digital",
"mammograms",
"at",
"baseline",
"and",
"month",
"12",
"time",
"points",
"in",
"932",
"completers",
"(",
"462",
"in",
"GTE",
"and",
"470",
"in",
"placebo",
")",
".",
"GTE",
"supplementation",
"for",
"12",
"months",
"did",
"not",
"significantly",
"change",
"percent",
"MD",
"(",
"PMD",
")",
"or",
"absolute",
"MD",
"in",
"all",
"women",
".",
"In",
"younger",
"women",
"(",
"50",
"-",
"55",
"years",
")",
",",
"GTE",
"supplementation",
"significantly",
"reduced",
"PMD",
"by",
"4.40",
"%",
"as",
"compared",
"with",
"the",
"placebo",
"with",
"a",
"1.02",
"%",
"PMD",
"increase",
"from",
"pre-",
"to",
"postintervention",
"(",
"P",
"=",
"0.05",
")",
",",
"but",
"had",
"no",
"effect",
"in",
"older",
"women",
"(",
"Pinteraction",
"=",
"0.07",
")",
".",
"GTE",
"supplementation",
"did",
"not",
"induce",
"MD",
"change",
"in",
"other",
"subgroups",
"of",
"women",
"stratified",
"by",
"catechol",
"-",
"O",
"-",
"methyltransferase",
"genotype",
"or",
"level",
"of",
"body",
"mass",
"index",
".",
"In",
"conclusion",
",",
"1",
"-year",
"supplementation",
"with",
"a",
"high",
"dose",
"of",
"EGCG",
"did",
"not",
"have",
"a",
"significant",
"effect",
"on",
"MD",
"measures",
"in",
"all",
"women",
",",
"but",
"reduced",
"PMD",
"in",
"younger",
"women",
",",
"an",
"age",
"-",
"dependent",
"effect",
"similar",
"to",
"those",
"of",
"tamoxifen",
".",
"Further",
"investigation",
"of",
"the",
"potential",
"chemopreventive",
"effect",
"of",
"green",
"tea",
"intake",
"on",
"breast",
"cancer",
"risk",
"in",
"younger",
"women",
"is",
"warranted",
".",
"Cancer",
"Prev",
"Res",
";",
"10",
"(",
"12",
")",
";",
"710",
"-",
"8",
".",
"©",
"2017",
"AACR",
"."
] | [
0,
0,
0,
0,
0,
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
3,
0,
0,
0,
5,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
21 | [
"Effectiveness",
"of",
"Tailored",
"Rehabilitation",
"Education",
"in",
"Improving",
"the",
"Health",
"Literacy",
"and",
"Health",
"Status",
"of",
"Postoperative",
"Patients",
"With",
"Breast",
"Cancer",
":",
"A",
"Randomized",
"Controlled",
"Trial",
".",
"The",
"improvement",
"of",
"breast",
"cancer",
"treatment",
"and",
"the",
"extension",
"of",
"survivorship",
"have",
"led",
"to",
"the",
"development",
"of",
"postoperative",
"complications",
"among",
"cancer",
"survivors",
".",
"Health",
"literacy",
"(",
"HL",
")",
",",
"defined",
"as",
"patients",
"'",
"capability",
"of",
"using",
"health",
"information",
"to",
"maintain",
"their",
"health",
"status",
",",
"can",
"enable",
"breast",
"cancer",
"patients",
"to",
"manage",
"postoperative",
"complications",
".",
"The",
"aims",
"of",
"this",
"study",
"were",
"to",
"develop",
"a",
"tailored",
"rehabilitation",
"education",
"(",
"TRE",
")",
"program",
"and",
"examine",
"the",
"effectiveness",
"of",
"this",
"program",
"in",
"improving",
"the",
"HL",
"and",
"health",
"status",
"with",
"breast",
"cancer",
".",
"This",
"randomized",
"controlled",
"trial",
"recruited",
"99",
"breast",
"cancer",
"patients",
"(",
"49",
"and",
"50",
"in",
"the",
"intervention",
"and",
"control",
"groups",
",",
"respectively",
")",
"within",
"1",
"week",
"after",
"surgery",
".",
"Four",
"-",
"week",
"individualized",
"TRE",
"programs",
"were",
"implemented",
"to",
"improve",
"their",
"HL",
"and",
"health",
"status",
".",
"Our",
"results",
"showed",
"that",
"the",
"TRE",
"program",
"produced",
"significant",
"improvements",
"in",
"HL",
"and",
"health",
"status",
"in",
"the",
"components",
"of",
"the",
"International",
"Classification",
"of",
"Functioning",
",",
"Disability",
"and",
"Health",
".",
"However",
",",
"no",
"significant",
"difference",
"was",
"observed",
"in",
"the",
"activity",
"scores",
"obtained",
"using",
"the",
"Barthel",
"Index",
"between",
"the",
"2",
"groups",
".",
"Our",
"finding",
"supports",
"the",
"effectiveness",
"of",
"1",
"-month",
"TRE",
"in",
"improving",
"HL",
"and",
"all",
"components",
"of",
"the",
"International",
"Classification",
"of",
"Functioning",
",",
"Disability",
"and",
"Health",
"status",
",",
"except",
"the",
"activity",
"component",
"among",
"breast",
"cancer",
"in",
"Taiwan",
".",
"Clinicians",
"could",
"incorporate",
"the",
"TRE",
"techniques",
"in",
"the",
"rehabilitation",
"sessions",
"according",
"to",
"the",
"healthcare",
",",
"disease",
"prevention",
",",
"and",
"health",
"promotion",
"domains",
"to",
"improve",
"the",
"clinical",
"outcomes",
"as",
"well",
"as",
"change",
"their",
"health",
"behaviors",
"and",
"attitudes",
"of",
"patients",
"with",
"breast",
"cancer",
"."
] | [
0,
0,
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
3,
0,
5,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
22 | [
"High",
"-",
"dose",
"chemotherapy",
"with",
"haematopoietic",
"stem",
"cell",
"transplantation",
"for",
"metastatic",
"breast",
"cancer",
"patients",
":",
"final",
"results",
"of",
"the",
"French",
"multicentric",
"randomised",
"CMA",
"/",
"PEGASE",
"04",
"protocol",
".",
"The",
"aim",
"of",
"our",
"study",
"was",
"to",
"evaluate",
"the",
"impact",
"on",
"time",
"to",
"progression",
"(",
"TTP",
")",
"and",
"overall",
"survival",
"(",
"OS",
")",
"of",
"high",
"-",
"dose",
"chemotherapy",
"(",
"HD",
"-",
"CT",
")",
"over",
"conventional",
"CT",
"in",
"metastatic",
"breast",
"cancer",
"patients",
".",
"Between",
"09",
"/",
"92",
"and",
"12",
"/",
"96",
",",
"61",
"patients",
"with",
"chemosensitive",
"metastatic",
"breast",
"cancer",
"were",
"randomised",
"between",
"HD",
"-",
"CT",
"using",
"the",
"CMA",
"regimen",
"(",
"Mitoxantrone",
",",
"Cyclophosphamide",
",",
"Melphalan",
")",
"applied",
"as",
"consolidation",
"(",
"32",
"patients",
")",
"or",
"maintenance",
"CT",
"(",
"29",
"patients",
")",
".",
"At",
"randomisation",
",",
"13",
"patients",
"were",
"in",
"complete",
"response",
",",
"47",
"in",
"partial",
"response",
"and",
"one",
"had",
"stable",
"disease",
".",
"The",
"median",
"TTPs",
"from",
"randomisation",
"were",
"6",
"and",
"12",
"months",
"in",
"the",
"standard",
"and",
"intensive",
"groups",
",",
"respectively",
"(",
"P",
"<",
"0.0056",
")",
",",
"with",
"a",
"relapse",
"rate",
"of",
"86.2",
"%",
"vs.",
"62.5",
"%",
"at",
"2",
"years",
",",
"and",
"100",
"%",
"vs.",
"81.3",
"%",
"at",
"5",
"years",
".",
"The",
"median",
"OS",
"times",
"were",
"19.3",
"and",
"44.1",
"months",
",",
"with",
"an",
"OS",
"rate",
"of",
"13.8",
"%",
"vs.",
"36.8",
"%",
"at",
"5",
"years",
"(",
"P",
"<",
"0.0294",
")",
".",
"The",
"CMA",
"regimen",
"could",
"prolong",
"the",
"TTP",
"of",
"patients",
"with",
"chemosensitive",
"metastatic",
"breast",
"cancer",
".",
"Further",
"studies",
"are",
"needed",
"to",
"determine",
"if",
"this",
"translates",
"into",
"an",
"effect",
"on",
"OS",
"."
] | [
17,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
21,
22,
0,
0,
0,
21,
22,
0,
0,
21,
22,
0,
0,
0,
37,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
31,
32,
21,
22,
22,
0,
0,
29,
30,
0,
31,
32,
21,
22,
22,
0,
0,
21,
22,
22,
0,
37,
0,
39,
40,
0,
0,
0,
21,
22,
0,
29,
30,
0,
31,
32,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
23 | [
"High",
"-",
"dose",
"chemotherapy",
"with",
"hematopoietic",
"stem",
"-",
"cell",
"rescue",
"for",
"high",
"-",
"risk",
"breast",
"cancer",
".",
"The",
"use",
"of",
"high",
"-",
"dose",
"adjuvant",
"chemotherapy",
"for",
"high",
"-",
"risk",
"primary",
"breast",
"cancer",
"is",
"controversial",
".",
"We",
"studied",
"its",
"efficacy",
"in",
"patients",
"with",
"4",
"to",
"9",
"or",
"10",
"or",
"more",
"tumor",
"-",
"positive",
"axillary",
"lymph",
"nodes",
".",
"Patients",
"younger",
"than",
"56",
"years",
"of",
"age",
"who",
"had",
"undergone",
"surgery",
"for",
"breast",
"cancer",
"and",
"who",
"had",
"no",
"distant",
"metastases",
"were",
"eligible",
"if",
"they",
"had",
"at",
"least",
"four",
"tumor",
"-",
"positive",
"axillary",
"lymph",
"nodes",
".",
"Patients",
"in",
"the",
"conventional",
"-",
"dose",
"group",
"received",
"fluorouracil",
",",
"epirubicin",
",",
"and",
"cyclophosphamide",
"(",
"FEC",
")",
"every",
"three",
"weeks",
"for",
"five",
"courses",
",",
"followed",
"by",
"radiotherapy",
"and",
"tamoxifen",
".",
"The",
"high",
"-",
"dose",
"treatment",
"was",
"identical",
",",
"except",
"that",
"high",
"-",
"dose",
"chemotherapy",
"(",
"6",
"g",
"of",
"cyclophosphamide",
"per",
"square",
"meter",
"of",
"body",
"-",
"surface",
"area",
",",
"480",
"mg",
"of",
"thiotepa",
"per",
"square",
"meter",
",",
"and",
"1600",
"mg",
"of",
"carboplatin",
"per",
"square",
"meter",
")",
"with",
"autologous",
"peripheral",
"-",
"blood",
"hematopoietic",
"progenitor",
"-",
"cell",
"transplantation",
"replaced",
"the",
"fifth",
"course",
"of",
"FEC",
".",
"Of",
"the",
"885",
"patients",
",",
"442",
"were",
"assigned",
"to",
"the",
"high",
"-",
"dose",
"group",
"and",
"443",
"to",
"the",
"conventional",
"-",
"dose",
"group",
".",
"After",
"a",
"median",
"follow",
"-",
"up",
"of",
"57",
"months",
",",
"the",
"actuarial",
"5",
"-year",
"relapse",
"-",
"free",
"survival",
"rates",
"were",
"59",
"percent",
"in",
"the",
"conventional",
"-",
"dose",
"group",
"and",
"65",
"percent",
"in",
"the",
"high",
"-",
"dose",
"group",
"(",
"hazard",
"ratio",
"for",
"relapse",
"in",
"the",
"high",
"-",
"dose",
"group",
",",
"0.83",
";",
"95",
"percent",
"confidence",
"interval",
",",
"0.66",
"to",
"1.03",
";",
"P=",
"0.09",
")",
".",
"In",
"the",
"group",
"with",
"10",
"or",
"more",
"positive",
"nodes",
",",
"the",
"relapse",
"-",
"free",
"survival",
"rates",
"were",
"51",
"percent",
"in",
"the",
"conventional",
"-",
"dose",
"group",
"and",
"61",
"percent",
"in",
"the",
"high",
"-",
"dose",
"group",
"(",
"P=",
"0.05",
"by",
"the",
"log",
"-",
"rank",
"test",
";",
"hazard",
"ratio",
"for",
"relapse",
",",
"0.71",
";",
"95",
"percent",
"confidence",
"interval",
",",
"0.50",
"to",
"1.00",
")",
".",
"High",
"-",
"dose",
"alkylating",
"therapy",
"improves",
"relapse",
"-",
"free",
"survival",
"among",
"patients",
"with",
"stage",
"II",
"or",
"III",
"breast",
"cancer",
"and",
"10",
"or",
"more",
"positive",
"axillary",
"lymph",
"nodes",
".",
"This",
"benefit",
"may",
"be",
"confined",
"to",
"patients",
"with",
"HER-",
"2",
"/",
"neu",
"-",
"negative",
"tumors",
"."
] | [
17,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
19,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
24 | [
"Race",
"and",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
"outcomes",
"in",
"a",
"randomized",
"chemotherapy",
"trial",
".",
"The",
"association",
"between",
"black",
"race",
"and",
"worse",
"outcomes",
"in",
"operable",
"breast",
"cancer",
"reported",
"in",
"previous",
"studies",
"has",
"been",
"attributed",
"to",
"a",
"higher",
"incidence",
"of",
"more",
"aggressive",
"triple",
"-",
"negative",
"disease",
",",
"disparities",
"in",
"care",
",",
"and",
"comorbidities",
".",
"We",
"evaluated",
"associations",
"between",
"black",
"race",
"and",
"outcomes",
",",
"by",
"tumor",
"hormone",
"receptor",
"and",
"HER",
"2",
"expression",
",",
"in",
"patients",
"who",
"were",
"treated",
"with",
"contemporary",
"adjuvant",
"therapy",
".",
"The",
"effect",
"of",
"black",
"race",
"on",
"disease",
"-",
"free",
"and",
"overall",
"survival",
"was",
"evaluated",
"using",
"Cox",
"proportional",
"hazards",
"models",
"adjusted",
"for",
"multiple",
"covariates",
"in",
"a",
"clinical",
"trial",
"population",
"that",
"was",
"treated",
"with",
"anthracycline-",
"and",
"taxane",
"-",
"containing",
"chemotherapy",
".",
"Categorical",
"variables",
"were",
"compared",
"using",
"the",
"Fisher",
"exact",
"test",
".",
"All",
"P",
"values",
"are",
"two",
"-",
"sided",
".",
"Of",
"4817",
"eligible",
"patients",
",",
"405",
"(",
"8.4",
"%",
")",
"were",
"black",
".",
"Compared",
"with",
"nonblack",
"patients",
",",
"black",
"patients",
"had",
"a",
"higher",
"rate",
"of",
"triple",
"-",
"negative",
"disease",
"(",
"31.9",
"%",
"vs",
"17.2",
"%",
";",
"P",
"<",
".",
"001",
")",
"and",
"a",
"higher",
"body",
"mass",
"index",
"(",
"median",
":",
"31.7",
"vs",
"27.4",
"kg",
"/",
"m",
"(",
"2",
")",
";",
"P",
"<",
".",
"001",
")",
".",
"Black",
"race",
"was",
"statistically",
"significantly",
"associated",
"with",
"worse",
"disease",
"-",
"free",
"survival",
"(",
"5",
"-year",
"disease",
"-",
"free",
"survival",
",",
"black",
"vs",
"nonblack",
":",
"76.7",
"%",
"vs",
"84.5",
"%",
";",
"hazard",
"ratio",
"of",
"recurrence",
"or",
"death",
"=",
"1.58",
",",
"95",
"%",
"confidence",
"interval",
"=",
"1.19",
"to",
"2.10",
",",
"P",
"=",
".",
"0015",
")",
"and",
"overall",
"survival",
"(",
"5",
"-year",
"overall",
"survival",
",",
"black",
"vs",
"nonblack",
":",
"87.6",
"%",
"vs",
"91.9",
"%",
";",
"hazard",
"ratio",
"of",
"death",
"=",
"1.49",
",",
"95",
"%",
"confidence",
"interval",
"=",
"1.05",
"to",
"2.12",
",",
"P",
"=",
".",
"025",
")",
"in",
"patients",
"with",
"hormone",
"receptor",
"-",
"positive",
"HER",
"2",
"-",
"negative",
"disease",
"but",
"not",
"in",
"patients",
"with",
"triple",
"-",
"negative",
"or",
"HER",
"2",
"-",
"positive",
"disease",
".",
"In",
"a",
"model",
"that",
"included",
"black",
"race",
",",
"hormone",
"receptor",
"-",
"positive",
"HER",
"2",
"-",
"negative",
"disease",
"vs",
"other",
"subtypes",
",",
"and",
"their",
"interaction",
",",
"the",
"interaction",
"term",
"was",
"statistically",
"significant",
"for",
"disease",
"-",
"free",
"survival",
"(",
"P",
"=",
".",
"027",
")",
"but",
"not",
"for",
"overall",
"survival",
"(",
"P",
"=",
".",
"086",
")",
".",
"Factors",
"other",
"than",
"disparities",
"in",
"care",
"or",
"aggressive",
"disease",
"contribute",
"to",
"increased",
"recurrence",
"in",
"black",
"women",
"with",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
12,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
3,
0,
0,
0,
0,
0,
11,
0,
0,
0,
19,
0,
0,
17,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
25 | [
"Exemestane",
"for",
"breast",
"cancer",
"prevention",
":",
"a",
"critical",
"shift",
"?",
"The",
"Mammary",
"Prevention",
"3",
"(",
"MAP",
".",
"3",
")",
"placebo",
"-",
"controlled",
"randomized",
"trial",
"in",
"4",
",",
"560",
"high",
"-",
"risk",
"postmenopausal",
"women",
"showed",
"a",
"65",
"%",
"reduction",
"in",
"invasive",
"breast",
"cancer",
"with",
"the",
"use",
"of",
"exemestane",
"at",
"35",
"months",
"median",
"follow",
"-",
"up",
".",
"Few",
"differences",
"in",
"adverse",
"events",
"were",
"observed",
"between",
"the",
"arms",
",",
"suggesting",
"a",
"promising",
"risk",
":",
"benefit",
"balance",
"with",
"exemestane",
"for",
"use",
"in",
"chemoprevention",
".",
"Yet",
",",
"the",
"MAP",
".",
"3",
"design",
"and",
"implementation",
"raise",
"concerns",
"regarding",
"limited",
"data",
"maturity",
"and",
"not",
"prospectively",
"including",
"key",
"bone",
"-",
"related",
"and",
"other",
"toxicities",
"as",
"study",
"end",
"points",
".",
"Exemestane",
"for",
"prevention",
"is",
"juxtaposed",
"against",
"selective",
"estrogen",
"receptor",
"modulators",
"and",
"the",
"other",
"aromatase",
"inhibitors",
".",
"Additional",
"issues",
"for",
"prevention",
",",
"including",
"the",
"influence",
"of",
"obesity",
",",
"alternative",
"dosing",
",",
"and",
"biomarker",
"use",
"in",
"phase",
"III",
"trials",
",",
"are",
"addressed",
".",
"The",
"recently",
"completed",
"MAP",
".",
"3",
"trial",
"of",
"exemestane",
"for",
"breast",
"cancer",
"prevention",
"offers",
"a",
"potential",
"new",
"standard",
"for",
"pharmaceutical",
"risk",
"reduction",
"in",
"high",
"-",
"risk",
"postmenopausal",
"women",
".",
"In",
"addition",
"to",
"describing",
"key",
"findings",
"from",
"the",
"publication",
"of",
"MAP",
".",
"3",
"and",
"related",
"trials",
",",
"our",
"review",
"undertakes",
"a",
"detailed",
"analysis",
"of",
"the",
"strengths",
"and",
"weaknesses",
"of",
"MAP",
".",
"3",
"as",
"well",
"as",
"the",
"implications",
"for",
"future",
"prevention",
"research",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
10,
10,
0,
0,
29,
30,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
26 | [
"The",
"Patient",
"'s",
"Anastrozole",
"Compliance",
"to",
"Therapy",
"(",
"PACT",
")",
"Program",
":",
"a",
"randomized",
",",
"in",
"-",
"practice",
"study",
"on",
"the",
"impact",
"of",
"a",
"standardized",
"information",
"program",
"on",
"persistence",
"and",
"compliance",
"to",
"adjuvant",
"endocrine",
"therapy",
"in",
"postmenopausal",
"women",
"with",
"early",
"breast",
"cancer",
".",
"Compliance",
"and",
"persistence",
"are",
"often",
"overlooked",
"in",
"adjuvant",
"breast",
"cancer",
"treatment",
".",
"PACT",
"was",
"a",
"prospective",
",",
"multicenter",
",",
"randomized",
",",
"open",
",",
"parallel",
"-",
"group",
"study",
"assessing",
"whether",
"educational",
"materials",
"(",
"EMs",
")",
"enhanced",
"compliance",
"with",
"aromatase",
"inhibitor",
"(",
"AI",
")",
"therapy",
"in",
"postmenopausal",
"women",
"with",
"early",
",",
"hormone",
"-",
"receptor",
"-",
"positive",
"(",
"HR+",
")",
"breast",
"cancer",
".",
"The",
"primary",
"end",
"points",
"were",
"compliance",
"(",
"proportion",
"taking",
"≥",
"80",
"%",
"anastrozole",
")",
"at",
"12",
"months",
"and",
"persistence",
"(",
"proportion",
"reporting",
"anastrozole",
"intake",
"during",
"the",
"study",
"period",
")",
".",
"Four",
"thousand",
"eight",
"hundred",
"and",
"forty",
"-",
"four",
"patients",
"were",
"randomly",
"assigned",
"1",
":1",
"to",
"receive",
"standard",
"therapy",
"or",
"standard",
"therapy",
"with",
"EMs",
".",
"There",
"was",
"no",
"difference",
"between",
"arms",
"in",
"compliance",
"(",
"N",
"=",
"2740",
";",
"88.5",
"%",
"/",
"88.8",
"%",
",",
"respectively",
",",
"P",
"=",
"0.81",
")",
"or",
"persistence",
"rates",
"(",
"N",
"=",
"2740",
";",
"40.5",
"%",
"/",
"43.0",
"%",
",",
"respectively",
",",
"P",
"=",
"0.18",
")",
".",
"Modified",
"end",
"point",
"analyses",
"found",
"no",
"differences",
"in",
"compliance",
"between",
"arms",
"based",
"on",
"the",
"classification",
"of",
":",
"(",
"i",
")",
"patients",
"with",
"missing",
"documentation",
"or",
"follow",
"-",
"up",
"visit",
"<",
"9",
"months",
"as",
"non",
"-",
"compliant",
"(",
"N",
"=",
"4397",
",",
"P",
"=",
"0.15",
")",
";",
"(",
"ii",
")",
"patients",
"with",
"early",
"(",
"≤",
"292",
"days",
")",
"12",
"-month",
"follow",
"-",
"up",
"documentation",
"excluded",
"(",
"N",
"=",
"4091",
",",
"P",
"=",
"0.19",
")",
";",
"(",
"iii",
")",
"patients",
"reaching",
"≥",
"80",
"%",
"compliance",
"during",
"individual",
"follow",
"-",
"up",
"as",
"compliant",
"(",
"N",
"=",
"4397",
",",
"P",
"=",
"0.26",
")",
".",
"Modified",
"persistence",
"analyses",
"found",
"no",
"difference",
"between",
"arms",
"(",
"N",
"=",
"4397",
",",
"P",
"=",
"0.37",
")",
".",
"Addition",
"of",
"EMs",
"to",
"standard",
"therapy",
"did",
"not",
"significantly",
"affect",
"compliance",
"and",
"persistence",
"with",
"adjuvant",
"anastrozole",
".",
"CLINICALTRIALS",
"ID",
":",
"NCT",
"00555867",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
2,
2,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
27 | [
"Phase",
"III",
"trial",
"comparing",
"doxorubicin",
"plus",
"cyclophosphamide",
"with",
"docetaxel",
"plus",
"cyclophosphamide",
"as",
"adjuvant",
"therapy",
"for",
"operable",
"breast",
"cancer",
".",
"The",
"combination",
"of",
"doxorubicin",
"and",
"cyclophosphamide",
"(",
"AC",
")",
"is",
"a",
"standard",
"adjuvant",
"chemotherapy",
"regimen",
".",
"Studies",
"of",
"docetaxel",
"and",
"cyclophosphamide",
"(",
"TC",
")",
"in",
"metastatic",
"breast",
"cancer",
"(",
"MBC",
")",
"showed",
"promise",
"in",
"MBC",
".",
"In",
"1997",
",",
"we",
"initiated",
"a",
"randomized",
"adjuvant",
"trial",
"of",
"TC",
"compared",
"with",
"standard",
"-",
"dose",
"AC",
"with",
"a",
"primary",
"end",
"point",
"of",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
".",
"Patients",
"were",
"eligible",
"if",
"they",
"had",
"stage",
"I",
"to",
"III",
"operable",
"invasive",
"breast",
"cancer",
"with",
"complete",
"surgical",
"excision",
"of",
"the",
"primary",
"tumor",
".",
"Between",
"June",
"1997",
"and",
"December",
"1999",
",",
"1",
",",
"016",
"patients",
"were",
"randomly",
"assigned",
"to",
"four",
"cycles",
"of",
"either",
"standard",
"-",
"dose",
"AC",
"(",
"60",
"and",
"600",
"mg",
"/",
"m",
"2",
",",
"respectively",
";",
"n",
"=",
"510",
")",
"or",
"TC",
"(",
"75",
"and",
"600",
"mg",
"/",
"m",
"2",
",",
"respectively",
";",
"n",
"=",
"506",
")",
",",
"administered",
"intravenously",
"every",
"3",
"weeks",
"as",
"adjuvant",
"chemotherapy",
".",
"Radiation",
"therapy",
"(",
"as",
"indicated",
")",
"and",
"tamoxifen",
",",
"for",
"patients",
"with",
"hormone",
"receptor",
"-",
"positive",
"disease",
",",
"were",
"administered",
"after",
"completion",
"of",
"chemotherapy",
".",
"Both",
"treatment",
"groups",
"(",
"TC",
"and",
"AC",
")",
"were",
"well",
"balanced",
"with",
"respect",
"to",
"major",
"prognostic",
"factors",
".",
"Patients",
"were",
"observed",
"through",
"2005",
"for",
"a",
"median",
"of",
"5.5",
"years",
".",
"At",
"5",
"years",
",",
"DFS",
"rate",
"was",
"significantly",
"superior",
"for",
"TC",
"compared",
"with",
"AC",
"(",
"86",
"%",
"v",
"80",
"%",
",",
"respectively",
";",
"hazard",
"ratio",
"[",
"HR",
"]",
"=",
"0.67",
";",
"95",
"%",
"CI",
",",
"0.50",
"to",
"0.94",
";",
"P",
"=",
".",
"015",
")",
".",
"Overall",
"survival",
"rates",
"for",
"TC",
"and",
"AC",
"were",
"90",
"%",
"and",
"87",
"%",
",",
"respectively",
"(",
"HR",
"=",
"0.76",
";",
"95",
"%",
"CI",
",",
"0.52",
"to",
"1.1",
";",
"P",
"=",
".",
"13",
")",
".",
"More",
"myalgia",
",",
"arthralgia",
",",
"edema",
",",
"and",
"febrile",
"neutropenia",
"occurred",
"on",
"the",
"TC",
"arm",
";",
"more",
"nausea",
"and",
"vomiting",
"occurred",
"on",
"the",
"AC",
"arm",
"as",
"well",
"as",
"one",
"incident",
"of",
"congestive",
"heart",
"failure",
".",
"At",
"5",
"years",
",",
"TC",
"was",
"associated",
"with",
"a",
"superior",
"DFS",
"and",
"a",
"different",
"toxicity",
"profile",
"compared",
"with",
"AC",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
28 | [
"Randomized",
",",
"controlled",
"trial",
"of",
"yoga",
"in",
"women",
"with",
"breast",
"cancer",
"undergoing",
"radiotherapy",
".",
"Previous",
"research",
"incorporating",
"yoga",
"(",
"YG",
")",
"into",
"radiotherapy",
"(",
"XRT",
")",
"for",
"women",
"with",
"breast",
"cancer",
"finds",
"improved",
"quality",
"of",
"life",
"(",
"QOL",
")",
".",
"However",
",",
"shortcomings",
"in",
"this",
"research",
"limit",
"the",
"findings",
".",
"Patients",
"with",
"stages",
"0",
"to",
"III",
"breast",
"cancer",
"were",
"recruited",
"before",
"starting",
"XRT",
"and",
"were",
"randomly",
"assigned",
"to",
"YG",
"(",
"n",
"=",
"53",
")",
"or",
"stretching",
"(",
"ST",
";",
"n",
"=",
"56",
")",
"three",
"times",
"a",
"week",
"for",
"6",
"weeks",
"during",
"XRT",
"or",
"waitlist",
"(",
"WL",
";",
"n",
"=",
"54",
")",
"control",
".",
"Self",
"-",
"report",
"measures",
"of",
"QOL",
"(",
"Medical",
"Outcomes",
"Study",
"36",
"-item",
"short",
"-",
"form",
"survey",
";",
"primary",
"outcomes",
")",
",",
"fatigue",
",",
"depression",
",",
"and",
"sleep",
"quality",
",",
"and",
"five",
"saliva",
"samples",
"per",
"day",
"for",
"3",
"consecutive",
"days",
"were",
"collected",
"at",
"baseline",
",",
"end",
"of",
"treatment",
",",
"and",
"1",
",",
"3",
",",
"and",
"6",
"months",
"later",
".",
"The",
"YG",
"group",
"had",
"significantly",
"greater",
"increases",
"in",
"physical",
"component",
"scale",
"scores",
"compared",
"with",
"the",
"WL",
"group",
"at",
"1",
"and",
"3",
"months",
"after",
"XRT",
"(",
"P",
"=",
".",
"01",
"and",
"P",
"=",
".",
"01",
")",
".",
"At",
"1",
",",
"3",
",",
"and",
"6",
"months",
",",
"the",
"YG",
"group",
"had",
"greater",
"increases",
"in",
"physical",
"functioning",
"compared",
"with",
"both",
"ST",
"and",
"WL",
"groups",
"(",
"P",
"<",
".",
"05",
")",
",",
"with",
"ST",
"and",
"WL",
"differences",
"at",
"only",
"3",
"months",
"(",
"P",
"<",
".",
"02",
")",
".",
"The",
"group",
"differences",
"were",
"similar",
"for",
"general",
"health",
"reports",
".",
"By",
"the",
"end",
"of",
"XRT",
",",
"the",
"YG",
"and",
"ST",
"groups",
"also",
"had",
"a",
"reduction",
"in",
"fatigue",
"(",
"P",
"<",
".",
"05",
")",
".",
"There",
"were",
"no",
"group",
"differences",
"for",
"mental",
"health",
"and",
"sleep",
"quality",
".",
"Cortisol",
"slope",
"was",
"steepest",
"for",
"the",
"YG",
"group",
"compared",
"with",
"the",
"ST",
"and",
"WL",
"groups",
"at",
"the",
"end",
"(",
"P",
"=",
".",
"023",
"and",
"P",
"=",
".",
"008",
")",
"and",
"1",
"month",
"after",
"XRT",
"(",
"P",
"=",
".",
"05",
"and",
"P",
"=",
".",
"04",
")",
".",
"YG",
"improved",
"QOL",
"and",
"physiological",
"changes",
"associated",
"with",
"XRT",
"beyond",
"the",
"benefits",
"of",
"simple",
"ST",
"exercises",
",",
"and",
"these",
"benefits",
"appear",
"to",
"have",
"long",
"-",
"term",
"durability",
"."
] | [
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
19,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
23,
0,
0,
23,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
29 | [
"Sensitivity",
"and",
"specificity",
"of",
"mammography",
"and",
"adjunctive",
"ultrasonography",
"to",
"screen",
"for",
"breast",
"cancer",
"in",
"the",
"Japan",
"Strategic",
"Anti",
"-",
"cancer",
"Randomized",
"Trial",
"(",
"J",
"-",
"START",
")",
":",
"a",
"randomised",
"controlled",
"trial",
".",
"Mammography",
"is",
"the",
"only",
"proven",
"method",
"for",
"breast",
"cancer",
"screening",
"that",
"reduces",
"mortality",
",",
"although",
"it",
"is",
"inaccurate",
"in",
"young",
"women",
"or",
"women",
"with",
"dense",
"breasts",
".",
"We",
"investigated",
"the",
"efficacy",
"of",
"adjunctive",
"ultrasonography",
".",
"Between",
"July",
",",
"2007",
",",
"and",
"March",
",",
"2011",
",",
"we",
"enrolled",
"asymptomatic",
"women",
"aged",
"40",
"-",
"49",
"years",
"at",
"42",
"study",
"sites",
"in",
"23",
"prefectures",
"into",
"the",
"Japan",
"Strategic",
"Anti",
"-",
"cancer",
"Randomized",
"Trial",
"(",
"J",
"-",
"START",
")",
".",
"Eligible",
"women",
"had",
"no",
"history",
"of",
"any",
"cancer",
"in",
"the",
"previous",
"5",
"years",
"and",
"were",
"expected",
"to",
"live",
"for",
"more",
"than",
"5",
"years",
".",
"Randomisation",
"was",
"done",
"centrally",
"by",
"the",
"Japan",
"Clinical",
"Research",
"Support",
"Unit",
".",
"Participants",
"were",
"randomly",
"assigned",
"in",
"1",
":1",
"ratio",
"to",
"undergo",
"mammography",
"and",
"ultrasonography",
"(",
"intervention",
"group",
")",
"or",
"mammography",
"alone",
"(",
"control",
"group",
")",
"twice",
"in",
"2",
"years",
".",
"The",
"primary",
"outcome",
"was",
"sensitivity",
",",
"specificity",
",",
"cancer",
"detection",
"rate",
",",
"and",
"stage",
"distribution",
"at",
"the",
"first",
"round",
"of",
"screening",
".",
"Analysis",
"was",
"by",
"intention",
"to",
"treat",
".",
"This",
"study",
"is",
"registered",
",",
"number",
"UMIN",
"000000757",
".",
"Of",
"72",
",",
"998",
"women",
"enrolled",
",",
"36",
",",
"859",
"were",
"assigned",
"to",
"the",
"intervention",
"group",
"and",
"36",
",",
"139",
"to",
"the",
"control",
"group",
".",
"Sensitivity",
"was",
"significantly",
"higher",
"in",
"the",
"intervention",
"group",
"than",
"in",
"the",
"control",
"group",
"(",
"91",
"·",
"1",
"%",
",",
"95",
"%",
"CI",
"87",
"·",
"2",
"-",
"95",
"·",
"0",
"vs",
"77",
"·",
"0",
"%",
",",
"70",
"·",
"3",
"-",
"83",
"·",
"7",
";",
"p=",
"0",
"·",
"0004",
")",
",",
"whereas",
"specificity",
"was",
"significantly",
"lower",
"(",
"87",
"·",
"7",
"%",
",",
"87",
"·",
"3",
"-",
"88",
"·",
"0",
"vs",
"91",
"·",
"4",
"%",
",",
"91",
"·",
"1",
"-",
"91",
"·",
"7",
";",
"p",
"<",
"0",
"·",
"0001",
")",
".",
"More",
"cancers",
"were",
"detected",
"in",
"the",
"intervention",
"group",
"than",
"in",
"the",
"control",
"group",
"(",
"184",
"[",
"0",
"·",
"50",
"%",
"]",
"vs",
"117",
"[",
"0",
"·",
"32",
"%",
"]",
",",
"p=",
"0",
"·",
"0003",
")",
"and",
"were",
"more",
"frequently",
"stage",
"0",
"and",
"I",
"(",
"144",
"[",
"71",
"·",
"3",
"%",
"]",
"vs",
"79",
"[",
"52",
"·",
"0",
"%",
"]",
",",
"p=",
"0",
"·",
"0194",
")",
".",
"18",
"(",
"0",
"·",
"05",
"%",
")",
"interval",
"cancers",
"were",
"detected",
"in",
"the",
"intervention",
"group",
"compared",
"with",
"35",
"(",
"0",
"·",
"10",
"%",
")",
"in",
"the",
"control",
"group",
"(",
"p=",
"0",
"·",
"034",
")",
".",
"Adjunctive",
"ultrasonography",
"increases",
"sensitivity",
"and",
"detection",
"rate",
"of",
"early",
"cancers",
".",
"Ministry",
"of",
"Health",
",",
"Labour",
"and",
"Welfare",
"of",
"Japan",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
23,
0,
23,
24,
24,
0,
0,
23,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
3,
4,
4,
0,
0,
0,
0,
0,
0,
0,
5,
6,
6,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
30,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
32,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
29,
30,
30,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
32,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
29,
30,
30,
30,
30,
0,
27,
0,
31,
32,
32,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
25,
0,
29,
30,
30,
30,
0,
0,
27,
0,
31,
32,
32,
32,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
29,
30,
30,
30,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
31,
32,
32,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
30 | [
"[",
"Treatment",
"of",
"advanced",
"metastatic",
"breast",
"cancer",
"with",
"exemestane",
",",
"a",
"multicenter",
"randomized",
"controlled",
"study",
"of",
"195",
"cases",
"]",
".",
"To",
"observe",
"the",
"efficacy",
"of",
"exemestane",
"for",
"postmenopausal",
"advanced",
"metastatic",
"breast",
"cancer",
",",
"and",
"to",
"assess",
"its",
"side",
"effects",
".",
"A",
"randomized",
",",
"double",
"-",
"blind",
",",
"and",
"parallel",
"controlled",
"study",
"was",
"conducted",
"among",
"195",
"patients",
"with",
"postmenopausal",
"advanced",
"metastatic",
"breast",
"cancer",
"from",
"December",
"2001",
"to",
"June",
"2002",
".",
"Except",
"for",
"the",
"4",
"cases",
"who",
"were",
"lost",
"to",
"follow",
"-",
"up",
",",
"the",
"remaining",
"191",
"patients",
"were",
"divided",
"into",
"two",
"groups",
":",
"study",
"group",
"(",
"n",
"=",
"96",
",",
"treated",
"with",
"exemestane",
"capsule",
"25",
"mg",
"and",
"one",
"model",
"tablet",
"of",
"letrozole",
"orally",
"q.",
"d.",
"for",
"8",
"weeks",
")",
",",
"and",
"control",
"group",
"(",
"n",
"=",
"95",
",",
"treated",
"with",
"letrozole",
"2.5",
"mg",
"and",
"one",
"model",
"capsule",
"of",
"exemestane",
"orally",
"q.",
"d.",
"for",
"8",
"weeks",
")",
".",
"Physical",
"examination",
",",
"roentgenography",
"and",
"CT",
"were",
"conducted",
"to",
"observe",
"the",
"outcome",
"of",
"the",
"tumor",
"and",
"the",
"level",
"of",
"estrogen",
"was",
"tested",
"2",
"weeks",
"before",
"and",
"4",
"and",
"8",
"weeks",
"after",
"the",
"beginning",
"of",
"treatment",
".",
"The",
"effective",
"rate",
"was",
"44.8",
"%",
"in",
"the",
"study",
"group",
"and",
"45.3",
"%",
"in",
"the",
"control",
"group",
"(",
"P",
"=",
"0.971",
")",
".",
"The",
"level",
"of",
"estradiol",
"was",
"5.17",
"+",
"/-",
"6.68",
"x",
"10",
"(",
"4",
")",
"pg",
"/",
"L",
"and",
"4.19",
"+",
"/-",
"3.06",
"x",
"10",
"(",
"4",
")",
"pg",
"/",
"L",
"in",
"the",
"study",
"group",
"and",
"control",
"group",
"respectively",
";",
"and",
"was",
"3.08",
"+",
"/-",
"2.80",
"x",
"10",
"(",
"4",
")",
"pg",
"/",
"L",
"and",
"2.76",
"+",
"/-",
"1.98",
"x",
"10",
"(",
"4",
")",
"pg",
"/",
"L",
"in",
"the",
"study",
"group",
"and",
"control",
"group",
"respectively",
"8",
"weeks",
"after",
"the",
"beginning",
"of",
"treatment",
",",
"both",
"decreased",
"by",
"43.7",
"%",
"in",
"comparison",
"with",
"those",
"before",
"treatment",
"(",
"both",
"P",
"<",
"0.001",
")",
",",
"however",
",",
"there",
"was",
"no",
"significant",
"difference",
"between",
"the",
"study",
"group",
"and",
"control",
"group",
"(",
"P",
"=",
"0.141",
")",
".",
"The",
"side",
"effects",
"of",
"exemestane",
"included",
"thirst",
",",
"giddiness",
",",
"and",
"nausea",
".",
"An",
"effective",
"hormonal",
"medicine",
",",
"exemestane",
"has",
"good",
"therapeutic",
"efficacy",
"in",
"postmenopausal",
"advanced",
"metastatic",
"breast",
"cancer",
"with",
"only",
"mild",
"side",
"effects",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
33,
0,
0,
41,
42,
42,
42,
42,
42,
42,
42,
42,
0,
35,
0,
0,
43,
44,
44,
44,
44,
44,
44,
44,
44,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
0,
41,
42,
42,
42,
42,
42,
42,
42,
42,
0,
35,
0,
0,
43,
44,
44,
44,
44,
44,
44,
44,
44,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
21,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
31 | [
"Mindfulness",
"based",
"stress",
"reduction",
"(",
"MBSR",
"(",
"BC",
")",
")",
"in",
"breast",
"cancer",
":",
"evaluating",
"fear",
"of",
"recurrence",
"(",
"FOR",
")",
"as",
"a",
"mediator",
"of",
"psychological",
"and",
"physical",
"symptoms",
"in",
"a",
"randomized",
"control",
"trial",
"(",
"RCT",
")",
".",
"To",
"investigate",
"the",
"mechanism",
"(",
"s",
")",
"of",
"action",
"of",
"mindfulness",
"based",
"stress",
"reduction",
"(",
"MBSR",
"(",
"BC",
")",
")",
"including",
"reductions",
"in",
"fear",
"of",
"recurrence",
"and",
"other",
"potential",
"mediators",
".",
"Eighty",
"-",
"two",
"post",
"-",
"treatment",
"breast",
"cancer",
"survivors",
"(",
"stages",
"0",
"-III",
")",
"were",
"randomly",
"assigned",
"to",
"a",
"6",
"-week",
"MBSR",
"(",
"BC",
")",
"program",
"(",
"n",
"=",
"40",
")",
"or",
"to",
"usual",
"care",
"group",
"(",
"UC",
")",
"(",
"n",
"=",
"42",
")",
".",
"Psychological",
"and",
"physical",
"variables",
"were",
"assessed",
"as",
"potential",
"mediators",
"at",
"baseline",
"and",
"at",
"6",
"weeks",
".",
"MBSR",
"(",
"BC",
")",
"compared",
"to",
"UC",
"experienced",
"favorable",
"changes",
"for",
"five",
"potential",
"mediators",
":",
"(",
"1",
")",
"change",
"in",
"fear",
"of",
"recurrence",
"problems",
"mediated",
"the",
"effect",
"of",
"MBSR",
"(",
"BC",
")",
"on",
"6",
"-week",
"change",
"in",
"perceived",
"stress",
"(",
"z",
"=",
"2.12",
",",
"p",
"=",
"0.03",
")",
"and",
"state",
"anxiety",
"(",
"z",
"=",
"2.03",
",",
"p",
"=",
"0.04",
")",
";",
"and",
"(",
"2",
")",
"change",
"in",
"physical",
"functioning",
"mediated",
"the",
"effect",
"of",
"MBSR",
"(",
"BC",
")",
"on",
"6",
"-week",
"change",
"in",
"perceived",
"stress",
"(",
"z",
"=",
"2.27",
",",
"p",
"=",
"0.02",
")",
"and",
"trait",
"anxiety",
"(",
"z",
"=",
"1.98",
",",
"p",
"=",
"0.05",
")",
".",
"MBSR",
"(",
"BC",
")",
"reduces",
"fear",
"of",
"recurrence",
"and",
"improves",
"physical",
"functioning",
"which",
"reduces",
"perceived",
"stress",
"and",
"anxiety",
".",
"Findings",
"support",
"the",
"beneficial",
"effects",
"of",
"MBSR",
"(",
"BC",
")",
"and",
"provide",
"insight",
"into",
"the",
"possible",
"cognitive",
"mechanism",
"of",
"action",
"."
] | [
17,
18,
18,
18,
18,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
19,
20,
20,
20,
20,
20,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
21,
22,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
32 | [
"Randomized",
"placebo",
"-",
"controlled",
"study",
"of",
"recombinant",
"human",
"interleukin-",
"11",
"to",
"prevent",
"chemotherapy",
"-",
"induced",
"thrombocytopenia",
"in",
"patients",
"with",
"breast",
"cancer",
"receiving",
"dose",
"-",
"intensive",
"cyclophosphamide",
"and",
"doxorubicin",
".",
"Thrombocytopenia",
"may",
"compromise",
"cancer",
"treatment",
",",
"causing",
"chemotherapy",
"dose",
"reductions",
",",
"schedule",
"alterations",
",",
"or",
"the",
"need",
"for",
"platelet",
"transfusions",
".",
"We",
"evaluated",
"the",
"efficacy",
"and",
"safety",
"of",
"recombinant",
"human",
"interleukin-",
"11",
"(",
"rhIL-",
"11",
";",
"Neumega",
",",
"Genetics",
"Institute",
",",
"Inc",
",",
"Cambridge",
",",
"MA",
")",
",",
"a",
"novel",
"thrombopoietic",
"growth",
"factor",
",",
"in",
"reducing",
"the",
"need",
"for",
"platelet",
"transfusions",
"in",
"patients",
"who",
"undergo",
"dose",
"-",
"intensive",
"chemotherapy",
".",
"Women",
"with",
"advanced",
"breast",
"cancer",
"received",
"cyclophosphamide",
"(",
"3",
",",
"200",
"mg",
"/",
"m",
"2",
")",
"and",
"doxorubicin",
"(",
"75",
"mg",
"/",
"m",
"2",
")",
"plus",
"granulocyte",
"colony",
"-",
"stimulating",
"factor",
"(",
"G",
"-",
"CSF",
";",
"5",
"microg",
"/",
"kg",
"/",
"d",
")",
".",
"Patients",
"were",
"randomized",
"to",
"blinded",
"treatment",
"with",
"placebo",
"or",
"50",
"microg",
"/",
"kg",
"/",
"d",
"rhIL-",
"11",
"subcutaneously",
"for",
"10",
"or",
"17",
"days",
"after",
"the",
"first",
"two",
"chemotherapy",
"cycles",
".",
"Seventy",
"-",
"seven",
"patients",
"were",
"randomized",
"and",
"constitute",
"the",
"intent",
"-",
"to",
"-",
"treat",
"(",
"ITT",
")",
"population",
".",
"Sixty",
"-",
"seven",
"patients",
"(",
"the",
"assessable",
"subgroup",
")",
"either",
"completed",
"both",
"cycles",
"without",
"a",
"major",
"protocol",
"violation",
"(",
"n",
"=",
"62",
")",
"or",
"received",
"a",
"platelet",
"transfusion",
"before",
"treatment",
"was",
"discontinued",
"after",
"the",
"first",
"cycle",
".",
"In",
"the",
"ITT",
"population",
",",
"rhIL-",
"11",
"significantly",
"decreased",
"the",
"requirement",
"for",
"platelet",
"transfusions",
";",
"27",
"of",
"40",
"(",
"68",
"%",
")",
"patients",
"who",
"received",
"rhIL-",
"11",
"did",
"not",
"require",
"transfusions",
",",
"compared",
"with",
"15",
"of",
"37",
"(",
"41",
"%",
")",
"in",
"the",
"placebo",
"group",
"(",
"P",
"=",
".",
"04",
")",
".",
"Treatment",
"with",
"rhIL-",
"11",
"significantly",
"reduced",
"the",
"total",
"number",
"of",
"platelet",
"transfusions",
"required",
"in",
"the",
"assessable",
"subgroup",
"(",
"P",
"=",
".",
"03",
")",
"and",
"the",
"time",
"to",
"platelet",
"recovery",
"to",
"more",
"than",
"50",
",",
"000",
"/microL",
"in",
"the",
"second",
"cycle",
"(",
"P",
"=",
".",
"01",
")",
".",
"Most",
"adverse",
"events",
"associated",
"with",
"rhIL-",
"11",
"were",
"reversible",
",",
"mild",
"to",
"moderate",
"in",
"severity",
",",
"and",
"likely",
"related",
"to",
"fluid",
"retention",
".",
"rhIL-",
"11",
"is",
"safe",
"and",
"effective",
"in",
"reducing",
"treatment",
"-",
"associated",
"thrombocytopenia",
"and",
"the",
"need",
"for",
"platelet",
"transfusions",
"in",
"patients",
"who",
"undergo",
"dose",
"-",
"intensive",
"chemotherapy",
",",
"and",
"thus",
"may",
"permit",
"chemotherapy",
"to",
"be",
"administered",
"as",
"planned",
"at",
"intended",
"doses",
"and",
"thereby",
"maximize",
"the",
"potential",
"for",
"a",
"successful",
"outcome",
"."
] | [
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
0,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
25,
0,
3,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
33 | [
"Effect",
"of",
"a",
"Scalp",
"Cooling",
"Device",
"on",
"Alopecia",
"in",
"Women",
"Undergoing",
"Chemotherapy",
"for",
"Breast",
"Cancer",
":",
"The",
"SCALP",
"Randomized",
"Clinical",
"Trial",
".",
"Chemotherapy",
"may",
"induce",
"alopecia",
".",
"Although",
"scalp",
"cooling",
"devices",
"have",
"been",
"used",
"to",
"prevent",
"this",
"alopecia",
",",
"efficacy",
"has",
"not",
"been",
"assessed",
"in",
"a",
"randomized",
"clinical",
"trial",
".",
"To",
"assess",
"whether",
"a",
"scalp",
"cooling",
"device",
"is",
"effective",
"at",
"reducing",
"chemotherapy",
"-",
"induced",
"alopecia",
"and",
"to",
"assess",
"adverse",
"treatment",
"effects",
".",
"Multicenter",
"randomized",
"clinical",
"trial",
"of",
"women",
"with",
"breast",
"cancer",
"undergoing",
"chemotherapy",
".",
"Patients",
"were",
"enrolled",
"from",
"December",
"9",
",",
"2013",
",",
"to",
"September",
"30",
",",
"2016",
".",
"One",
"interim",
"analysis",
"was",
"planned",
"to",
"allow",
"the",
"study",
"to",
"stop",
"early",
"for",
"efficacy",
".",
"Data",
"reported",
"are",
"from",
"the",
"interim",
"analysis",
".",
"This",
"study",
"was",
"conducted",
"at",
"7",
"sites",
"in",
"the",
"United",
"States",
",",
"and",
"182",
"women",
"with",
"breast",
"cancer",
"requiring",
"chemotherapy",
"were",
"enrolled",
"and",
"randomized",
".",
"Participants",
"were",
"randomized",
"to",
"scalp",
"cooling",
"(",
"n",
"=",
"119",
")",
"or",
"control",
"(",
"n",
"=",
"63",
")",
".",
"Scalp",
"cooling",
"was",
"done",
"using",
"a",
"scalp",
"cooling",
"device",
".",
"The",
"primary",
"efficacy",
"end",
"points",
"were",
"successful",
"hair",
"preservation",
"assessed",
"using",
"the",
"Common",
"Terminology",
"Criteria",
"for",
"Adverse",
"Events",
"version",
"4.0",
"scale",
"(",
"grade",
"0",
"[",
"no",
"hair",
"loss",
"]",
"or",
"grade",
"1",
"[",
"<",
"50",
"%",
"hair",
"loss",
"not",
"requiring",
"a",
"wig",
"]",
"were",
"considered",
"to",
"have",
"hair",
"preservation",
")",
"at",
"the",
"end",
"of",
"4",
"cycles",
"of",
"chemotherapy",
"by",
"a",
"clinician",
"unaware",
"of",
"treatment",
"assignment",
",",
"and",
"device",
"safety",
".",
"Secondary",
"end",
"points",
"included",
"wig",
"use",
"and",
"scores",
"on",
"the",
"European",
"Organisation",
"for",
"Research",
"and",
"Treatment",
"of",
"Cancer",
"Quality",
"of",
"Life",
"Questionnaire",
"-",
"Core",
"30",
",",
"Hospital",
"Anxiety",
"and",
"Depression",
"Scale",
",",
"and",
"a",
"summary",
"scale",
"of",
"the",
"Body",
"Image",
"Scale",
".",
"At",
"the",
"time",
"of",
"the",
"interim",
"analysis",
",",
"142",
"participants",
"were",
"evaluable",
".",
"The",
"mean",
"(",
"SD",
")",
"age",
"of",
"the",
"patients",
"was",
"52.6",
"(",
"10.1",
")",
"years",
";",
"36",
"%",
"(",
"n",
"=",
"51",
")",
"received",
"anthracycline",
"-",
"based",
"chemotherapy",
"and",
"64",
"%",
"(",
"n",
"=",
"91",
")",
"received",
"taxane",
"-",
"based",
"chemotherapy",
".",
"Successful",
"hair",
"preservation",
"was",
"found",
"in",
"48",
"of",
"95",
"women",
"with",
"cooling",
"(",
"50.5",
"%",
";",
"95",
"%",
"CI",
",",
"40.7",
"%",
"-",
"60.4",
"%",
")",
"compared",
"with",
"0",
"of",
"47",
"women",
"in",
"the",
"control",
"group",
"(",
"0",
"%",
";",
"95",
"%",
"CI",
",",
"0",
"%",
"-",
"7.6",
"%",
")",
"(",
"success",
"rate",
"difference",
",",
"50.5",
"%",
";",
"95",
"%",
"CI",
",",
"40.5",
"%",
"-",
"60.6",
"%",
")",
".",
"Because",
"the",
"1",
"-tailed",
"P",
"value",
"from",
"the",
"Fisher",
"exact",
"test",
"was",
"<",
".",
"001",
",",
"which",
"crossed",
"the",
"superiority",
"boundary",
"(",
"P",
"=",
".",
"0061",
")",
",",
"the",
"data",
"and",
"safety",
"monitoring",
"board",
"recommended",
"study",
"termination",
"on",
"September",
"26",
",",
"2016",
".",
"There",
"were",
"no",
"statistically",
"significant",
"differences",
"in",
"changes",
"in",
"any",
"of",
"the",
"scales",
"of",
"quality",
"of",
"life",
"from",
"baseline",
"to",
"chemotherapy",
"cycle",
"4",
"among",
"the",
"scalp",
"cooling",
"and",
"control",
"groups",
".",
"Only",
"adverse",
"events",
"related",
"to",
"device",
"use",
"were",
"collected",
";",
"54",
"adverse",
"events",
"were",
"reported",
"in",
"the",
"cooling",
"group",
",",
"all",
"grades",
"1",
"and",
"2",
".",
"There",
"were",
"no",
"serious",
"adverse",
"device",
"events",
".",
"Among",
"women",
"with",
"stage",
"I",
"to",
"II",
"breast",
"cancer",
"receiving",
"chemotherapy",
"with",
"a",
"taxane",
",",
"anthracycline",
",",
"or",
"both",
",",
"those",
"who",
"underwent",
"scalp",
"cooling",
"were",
"significantly",
"more",
"likely",
"to",
"have",
"less",
"than",
"50",
"%",
"hair",
"loss",
"after",
"the",
"fourth",
"chemotherapy",
"cycle",
"compared",
"with",
"those",
"who",
"received",
"no",
"scalp",
"cooling",
".",
"Further",
"research",
"is",
"needed",
"to",
"assess",
"longer",
"-",
"term",
"efficacy",
"and",
"adverse",
"effects",
".",
"clinicaltrials.gov",
"Identifier",
":",
"NCT",
"01986140",
"."
] | [
0,
0,
0,
17,
18,
18,
0,
13,
0,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
0,
0,
1,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
19,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
34 | [
"Acute",
"and",
"Short",
"-",
"term",
"Toxic",
"Effects",
"of",
"Conventionally",
"Fractionated",
"vs",
"Hypofractionated",
"Whole",
"-",
"Breast",
"Irradiation",
":",
"A",
"Randomized",
"Clinical",
"Trial",
".",
"The",
"most",
"appropriate",
"dose",
"fractionation",
"for",
"whole",
"-",
"breast",
"irradiation",
"(",
"WBI",
")",
"remains",
"uncertain",
".",
"To",
"assess",
"acute",
"and",
"6",
"-month",
"toxic",
"effects",
"and",
"quality",
"of",
"life",
"(",
"QOL",
")",
"with",
"conventionally",
"fractionated",
"WBI",
"(",
"CF",
"-",
"WBI",
")",
"vs",
"hypofractionated",
"WBI",
"(",
"HF",
"-",
"WBI",
")",
".",
"Unblinded",
"randomized",
"trial",
"of",
"CF",
"-",
"WBI",
"(",
"n",
"=",
"149",
";",
"50.00",
"Gy",
"/",
"25",
"fractions",
"+",
"boost",
"[",
"10.00",
"-",
"14.00",
"Gy",
"/",
"5",
"-",
"7",
"fractions",
"]",
")",
"vs",
"HF",
"-",
"WBI",
"(",
"n",
"=",
"138",
";",
"42.56",
"Gy",
"/",
"16",
"fractions",
"+",
"boost",
"[",
"10.00",
"-",
"12.50",
"Gy",
"/",
"4",
"-",
"5",
"fractions",
"]",
")",
"following",
"breast",
"-",
"conserving",
"surgery",
"administered",
"in",
"community",
"-",
"based",
"and",
"academic",
"cancer",
"centers",
"to",
"287",
"women",
"40",
"years",
"or",
"older",
"with",
"stage",
"0",
"to",
"II",
"breast",
"cancer",
"for",
"whom",
"WBI",
"without",
"addition",
"of",
"a",
"third",
"field",
"was",
"recommended",
";",
"76",
"%",
"of",
"study",
"participants",
"(",
"n",
"=",
"217",
")",
"were",
"overweight",
"or",
"obese",
".",
"Patients",
"were",
"enrolled",
"from",
"February",
"2011",
"through",
"February",
"2014",
"and",
"observed",
"for",
"a",
"minimum",
"of",
"6",
"months",
".",
"Administration",
"of",
"CF",
"-",
"WBI",
"or",
"HF",
"-",
"WBI",
".",
"Physician",
"-",
"reported",
"acute",
"and",
"6",
"-month",
"toxic",
"effects",
"using",
"National",
"Cancer",
"Institute",
"Common",
"Toxicity",
"Criteria",
",",
"and",
"patient",
"-",
"reported",
"QOL",
"using",
"the",
"Functional",
"Assessment",
"of",
"Cancer",
"Therapy",
"for",
"Patients",
"with",
"Breast",
"Cancer",
"(",
"FACT",
"-",
"B",
")",
".",
"All",
"analyses",
"were",
"intention",
"to",
"treat",
",",
"with",
"outcomes",
"compared",
"using",
"the",
"χ",
"2",
"test",
",",
"Cochran",
"-",
"Armitage",
"test",
",",
"and",
"ordinal",
"logistic",
"regression",
".",
"Of",
"287",
"participants",
",",
"149",
"were",
"randomized",
"to",
"CF",
"-",
"WBI",
"and",
"138",
"to",
"HF",
"-",
"WBI",
".",
"Treatment",
"arms",
"were",
"well",
"matched",
"for",
"baseline",
"characteristics",
",",
"including",
"FACT",
"-",
"B",
"total",
"score",
"(",
"HF",
"-",
"WBI",
",",
"120.1",
"vs",
"CF",
"-",
"WBI",
",",
"118.8",
";",
"P",
"=",
".",
"46",
")",
"and",
"individual",
"QOL",
"items",
"such",
"as",
"somewhat",
"or",
"more",
"lack",
"of",
"energy",
"(",
"HF",
"-",
"WBI",
",",
"38",
"%",
"vs",
"CF",
"-",
"WBI",
",",
"39",
"%",
";",
"P",
"=",
".",
"86",
")",
"and",
"somewhat",
"or",
"more",
"trouble",
"meeting",
"family",
"needs",
"(",
"HF",
"-",
"WBI",
",",
"10",
"%",
"vs",
"CF",
"-",
"WBI",
",",
"14",
"%",
";",
"P",
"=",
".",
"54",
")",
".",
"Maximum",
"physician",
"-",
"reported",
"acute",
"dermatitis",
"(",
"36",
"%",
"vs",
"69",
"%",
";",
"P",
"<",
".",
"001",
")",
",",
"pruritus",
"(",
"54",
"%",
"vs",
"81",
"%",
";",
"P",
"<",
".",
"001",
")",
",",
"breast",
"pain",
"(",
"55",
"%",
"vs",
"74",
"%",
";",
"P",
"=",
".",
"001",
")",
",",
"hyperpigmentation",
"(",
"9",
"%",
"vs",
"20",
"%",
";",
"P",
"=",
".",
"002",
")",
",",
"and",
"fatigue",
"(",
"9",
"%",
"vs",
"17",
"%",
";",
"P",
"=",
".",
"02",
")",
"during",
"irradiation",
"were",
"lower",
"in",
"patients",
"randomized",
"to",
"HF",
"-",
"WBI",
".",
"The",
"rate",
"of",
"overall",
"grade",
"2",
"or",
"higher",
"acute",
"toxic",
"effects",
"was",
"less",
"with",
"HF",
"-",
"WBI",
"than",
"with",
"CF",
"-",
"WBI",
"(",
"47",
"%",
"vs",
"78",
"%",
";",
"P",
"<",
".",
"001",
")",
".",
"Six",
"months",
"after",
"irradiation",
",",
"physicians",
"reported",
"less",
"fatigue",
"in",
"patients",
"randomized",
"to",
"HF",
"-",
"WBI",
"(",
"0",
"%",
"vs",
"6",
"%",
";",
"P",
"=",
".",
"01",
")",
",",
"and",
"patients",
"randomized",
"to",
"HF",
"-",
"WBI",
"reported",
"less",
"lack",
"of",
"energy",
"(",
"23",
"%",
"vs",
"39",
"%",
";",
"P",
"<",
".",
"001",
")",
"and",
"less",
"trouble",
"meeting",
"family",
"needs",
"(",
"3",
"%",
"vs",
"9",
"%",
";",
"P",
"=",
".",
"01",
")",
".",
"Multivariable",
"regression",
"confirmed",
"the",
"superiority",
"of",
"HF",
"-",
"WBI",
"in",
"terms",
"of",
"patient",
"-",
"reported",
"lack",
"of",
"energy",
"(",
"odds",
"ratio",
"[",
"OR",
"]",
",",
"0.39",
";",
"95",
"%",
"CI",
",",
"0.24",
"-",
"0.63",
")",
"and",
"trouble",
"meeting",
"family",
"needs",
"(",
"OR",
",",
"0.34",
";",
"95",
"%",
"CI",
",",
"0.16",
"-",
"0.75",
")",
".",
"Treatment",
"with",
"HF",
"-",
"WBI",
"appears",
"to",
"yield",
"lower",
"rates",
"of",
"acute",
"toxic",
"effects",
"than",
"CF",
"-",
"WBI",
"as",
"well",
"as",
"less",
"fatigue",
"and",
"less",
"trouble",
"meeting",
"family",
"needs",
"6",
"months",
"after",
"completing",
"radiation",
"therapy",
".",
"These",
"findings",
"should",
"be",
"communicated",
"to",
"patients",
"as",
"part",
"of",
"shared",
"decision",
"making",
".",
"clinicaltrials.gov",
"Identifier",
":",
"NCT",
"01266642",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
35 | [
"A",
"cancer",
"research",
"(",
"UK",
")",
"randomized",
"phase",
"II",
"study",
"of",
"idoxifene",
"in",
"patients",
"with",
"locally",
"advanced",
"/",
"metastatic",
"breast",
"cancer",
"resistant",
"to",
"tamoxifen",
".",
"Idoxifene",
"is",
"a",
"novel",
"selective",
"oestrogen",
"receptor",
"modulator",
"(",
"SERM",
")",
"which",
"had",
"greater",
"binding",
"affinity",
"for",
"the",
"oestrogen",
"receptor",
"(",
"ER",
")",
"and",
"reduced",
"agonist",
"activity",
"compared",
"with",
"tamoxifen",
"in",
"preclinical",
"studies",
".",
"In",
"a",
"randomized",
"phase",
"II",
"trial",
"in",
"56",
"postmenopausal",
"patients",
"with",
"progressive",
"locally",
"advanced",
"/",
"metastatic",
"breast",
"cancer",
"we",
"assessed",
"whether",
"idoxifene",
"showed",
"evidence",
"of",
"activity",
"compared",
"with",
"an",
"increased",
"40",
"mg",
"/",
"day",
"dose",
"of",
"tamoxifen",
"in",
"patients",
"who",
"had",
"previously",
"demonstrated",
"resistance",
"to",
"the",
"standard",
"20",
"mg",
"/",
"day",
"dose",
"of",
"tamoxifen",
".",
"Of",
"47",
"patients",
"eligible",
"for",
"response",
"(",
"25",
"idoxifene",
",",
"22",
"tamoxifen",
")",
",",
"two",
"partial",
"responses",
"and",
"two",
"disease",
"stabilizations",
"(",
"SD",
")",
"for",
">",
"6",
"months",
"were",
"seen",
"with",
"idoxifene",
"(",
"overall",
"clinical",
"benefit",
"rate",
"16",
"%",
",",
"95",
"%",
"CI",
"4.5",
"-",
"36.1",
"%",
")",
".",
"The",
"median",
"duration",
"of",
"clinical",
"benefit",
"was",
"9.8",
"months",
".",
"In",
"contrast",
",",
"no",
"objective",
"responses",
"were",
"seen",
"with",
"the",
"increased",
"40",
"mg",
"/",
"day",
"dose",
"of",
"tamoxifen",
",",
"although",
"two",
"patients",
"had",
"SD",
"for",
"7",
"and",
"14",
"months",
"(",
"clinical",
"benefit",
"rate",
"9",
"%",
",",
"95",
"%",
"CI",
"1.1",
"-",
"29.2",
"%",
")",
".",
"Idoxifene",
"was",
"well",
"tolerated",
"and",
"the",
"reported",
"possible",
"drug",
"-",
"related",
"toxicities",
"were",
"similar",
"in",
"frequency",
"to",
"those",
"with",
"tamoxifen",
"(",
"hot",
"flushes",
"13",
"%",
"vs",
"15",
"%",
",",
"mild",
"nausea",
"20",
"%",
"vs",
"15",
"%",
")",
".",
"Endocrine",
"and",
"lipid",
"analysis",
"in",
"both",
"groups",
"showed",
"a",
"similar",
"significant",
"fall",
"in",
"serum",
"follicle",
"-",
"stimulating",
"hormone",
"and",
"luteinizing",
"hormone",
"after",
"4",
"weeks",
",",
"together",
"with",
"a",
"significant",
"rise",
"in",
"sex",
"hormone",
"binding",
"globulin",
"levels",
"and",
"11",
"%",
"reduction",
"in",
"serum",
"cholesterol",
"levels",
".",
"In",
"conclusion",
",",
"while",
"idoxifene",
"was",
"associated",
"with",
"only",
"modest",
"evidence",
"of",
"clinical",
"activity",
"in",
"patients",
"with",
"tamoxifen",
"-",
"resistant",
"breast",
"cancer",
",",
"its",
"toxicity",
"profile",
"and",
"effects",
"on",
"endocrine",
"/",
"lipid",
"parameters",
"were",
"similar",
"to",
"those",
"of",
"tamoxifen",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
3,
0,
0,
5,
0,
0,
0,
25,
21,
22,
0,
25,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
37,
38,
0,
0,
0,
0,
27,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
21,
0,
0,
0,
0,
0,
0,
21,
22,
22,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
29,
30,
0,
31,
32,
0,
21,
22,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
36 | [
"Tamoxifen",
"for",
"the",
"prevention",
"of",
"breast",
"cancer",
":",
"current",
"status",
"of",
"the",
"National",
"Surgical",
"Adjuvant",
"Breast",
"and",
"Bowel",
"Project",
"P-",
"1",
"study",
".",
"Initial",
"findings",
"from",
"the",
"National",
"Surgical",
"Adjuvant",
"Breast",
"and",
"Bowel",
"Project",
"Breast",
"Cancer",
"Prevention",
"Trial",
"(",
"P-",
"1",
")",
"demonstrated",
"that",
"tamoxifen",
"reduced",
"the",
"risk",
"of",
"estrogen",
"receptor",
"-",
"positive",
"tumors",
"and",
"osteoporotic",
"fractures",
"in",
"women",
"at",
"increased",
"risk",
"for",
"breast",
"cancer",
".",
"Side",
"effects",
"of",
"varying",
"clinical",
"significance",
"were",
"observed",
".",
"The",
"trial",
"was",
"unblinded",
"because",
"of",
"the",
"positive",
"results",
",",
"and",
"follow",
"-",
"up",
"continued",
".",
"This",
"report",
"updates",
"our",
"initial",
"findings",
".",
"Women",
"(",
"n",
"=",
"13",
",",
"388",
")",
"were",
"randomly",
"assigned",
"to",
"receive",
"placebo",
"or",
"tamoxifen",
"for",
"5",
"years",
".",
"Rates",
"of",
"breast",
"cancer",
"and",
"other",
"events",
"were",
"compared",
"by",
"the",
"use",
"of",
"risk",
"ratios",
"(",
"RRs",
")",
"and",
"95",
"%",
"confidence",
"intervals",
"(",
"CIs",
")",
".",
"Estimates",
"of",
"the",
"net",
"benefit",
"from",
"5",
"years",
"of",
"tamoxifen",
"therapy",
"were",
"compared",
"by",
"age",
",",
"race",
",",
"and",
"categories",
"of",
"predicted",
"breast",
"cancer",
"risk",
".",
"Statistical",
"tests",
"were",
"two",
"-",
"sided",
".",
"After",
"7",
"years",
"of",
"follow",
"-",
"up",
",",
"the",
"cumulative",
"rate",
"of",
"invasive",
"breast",
"cancer",
"was",
"reduced",
"from",
"42.5",
"per",
"1000",
"women",
"in",
"the",
"placebo",
"group",
"to",
"24.8",
"per",
"1000",
"women",
"in",
"the",
"tamoxifen",
"group",
"(",
"RR",
"=",
"0.57",
",",
"95",
"%",
"CI",
"=",
"0.46",
"to",
"0.70",
")",
"and",
"the",
"cumulative",
"rate",
"of",
"noninvasive",
"breast",
"cancer",
"was",
"reduced",
"from",
"15.8",
"per",
"1000",
"women",
"in",
"the",
"placebo",
"group",
"to",
"10.2",
"per",
"1000",
"women",
"in",
"the",
"tamoxifen",
"group",
"(",
"RR",
"=",
"0.63",
",",
"95",
"%",
"CI",
"=",
"0.45",
"to",
"0.89",
")",
".",
"These",
"reductions",
"were",
"similar",
"to",
"those",
"seen",
"in",
"the",
"initial",
"report",
".",
"Tamoxifen",
"led",
"to",
"a",
"32",
"%",
"reduction",
"in",
"osteoporotic",
"fractures",
"(",
"RR",
"=",
"0.68",
",",
"95",
"%",
"CI",
"=",
"0.51",
"to",
"0.92",
")",
".",
"Relative",
"risks",
"of",
"stroke",
",",
"deep",
"-",
"vein",
"thrombosis",
",",
"and",
"cataracts",
"(",
"which",
"increased",
"with",
"tamoxifen",
")",
"and",
"of",
"ischemic",
"heart",
"disease",
"and",
"death",
"(",
"which",
"were",
"not",
"changed",
"with",
"tamoxifen",
")",
"were",
"also",
"similar",
"to",
"those",
"initially",
"reported",
".",
"Risks",
"of",
"pulmonary",
"embolism",
"were",
"approximately",
"11",
"%",
"lower",
"than",
"in",
"the",
"original",
"report",
",",
"and",
"risks",
"of",
"endometrial",
"cancer",
"were",
"about",
"29",
"%",
"higher",
",",
"but",
"these",
"differences",
"were",
"not",
"statistically",
"significant",
".",
"The",
"net",
"benefit",
"achieved",
"with",
"tamoxifen",
"varied",
"according",
"to",
"age",
",",
"race",
",",
"and",
"level",
"of",
"breast",
"cancer",
"risk",
".",
"Despite",
"the",
"potential",
"bias",
"caused",
"by",
"the",
"unblinding",
"of",
"the",
"P-",
"1",
"trial",
",",
"the",
"magnitudes",
"of",
"all",
"beneficial",
"and",
"undesirable",
"treatment",
"effects",
"of",
"tamoxifen",
"were",
"similar",
"to",
"those",
"initially",
"reported",
",",
"with",
"notable",
"reductions",
"in",
"breast",
"cancer",
"and",
"increased",
"risks",
"of",
"thromboembolic",
"events",
"and",
"endometrial",
"cancer",
".",
"Readily",
"identifiable",
"subsets",
"of",
"individuals",
"comprising",
"2.5",
"million",
"women",
"could",
"derive",
"a",
"net",
"benefit",
"from",
"the",
"drug",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
21,
22,
22,
22,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
37 | [
"Comparison",
"of",
"fulvestrant",
"versus",
"tamoxifen",
"for",
"the",
"treatment",
"of",
"advanced",
"breast",
"cancer",
"in",
"postmenopausal",
"women",
"previously",
"untreated",
"with",
"endocrine",
"therapy",
":",
"a",
"multinational",
",",
"double",
"-",
"blind",
",",
"randomized",
"trial",
".",
"To",
"evaluate",
"the",
"efficacy",
"and",
"tolerability",
"of",
"fulvestrant",
"(",
"Faslodex",
";",
"AstraZeneca",
"Pharmaceuticals",
"LP",
",",
"Wilmington",
",",
"DE",
")",
",",
"a",
"new",
"estrogen",
"receptor",
"(",
"ER",
")",
"antagonist",
"that",
"downregulates",
"ER",
"and",
"has",
"no",
"agonist",
"effects",
",",
"versus",
"tamoxifen",
",",
"an",
"antiestrogen",
"with",
"agonist",
"and",
"antagonist",
"effects",
",",
"for",
"the",
"treatment",
"of",
"advanced",
"breast",
"cancer",
"in",
"postmenopausal",
"women",
".",
"In",
"this",
"multicenter",
",",
"double",
"-",
"blind",
",",
"randomized",
"trial",
",",
"patients",
"with",
"metastatic",
"/",
"locally",
"advanced",
"breast",
"cancer",
"previously",
"untreated",
"for",
"advanced",
"disease",
"were",
"randomly",
"assigned",
"to",
"receive",
"either",
"fulvestrant",
"(",
"250",
"mg",
",",
"via",
"intramuscular",
"injection",
",",
"once",
"monthly",
";",
"n",
"=",
"313",
")",
"or",
"tamoxifen",
"(",
"20",
"mg",
",",
"orally",
",",
"once",
"daily",
";",
"n",
"=",
"274",
")",
".",
"Patients",
"'",
"tumors",
"were",
"positive",
"for",
"ER",
"(",
"ER+",
")",
"and/or",
"progesterone",
"receptor",
"(",
"PgR+",
")",
",",
"or",
"had",
"an",
"unknown",
"receptor",
"status",
".",
"At",
"a",
"median",
"follow",
"-",
"up",
"of",
"14.5",
"months",
",",
"there",
"was",
"no",
"significant",
"difference",
"between",
"fulvestrant",
"and",
"tamoxifen",
"for",
"the",
"primary",
"end",
"point",
"of",
"time",
"to",
"progression",
"(",
"TTP",
";",
"median",
"TTP",
",",
"6.8",
"months",
"and",
"8.3",
"months",
",",
"respectively",
";",
"hazard",
"ratio",
",",
"1.18",
";",
"95",
"%",
"CI",
",",
"0.98",
"to",
"1.44",
";",
"P",
"=",
".",
"088",
")",
".",
"In",
"a",
"prospectively",
"planned",
"subset",
"analysis",
"of",
"patients",
"with",
"known",
"ER+",
"and/or",
"PgR+",
"tumors",
"(",
"approximately",
"78",
"%",
")",
",",
"median",
"TTP",
"was",
"8.2",
"months",
"for",
"fulvestrant",
"and",
"8.3",
"months",
"for",
"tamoxifen",
"(",
"hazard",
"ratio",
",",
"1.10",
";",
"95",
"%",
"CI",
",",
"0.89",
"to",
"1.36",
";",
"P",
"=",
".",
"39",
")",
".",
"The",
"objective",
"response",
"rate",
"for",
"the",
"overall",
"population",
"was",
"31.6",
"%",
"with",
"fulvestrant",
"and",
"33.9",
"%",
"with",
"tamoxifen",
",",
"and",
"33.2",
"%",
"and",
"31.1",
"%",
",",
"respectively",
",",
"in",
"the",
"known",
"hormone",
"receptor",
"-",
"positive",
"subgroup",
".",
"Both",
"treatments",
"were",
"well",
"tolerated",
".",
"In",
"the",
"overall",
"population",
",",
"between",
"-",
"group",
"differences",
"in",
"efficacy",
"end",
"points",
"favored",
"tamoxifen",
",",
"and",
"statistical",
"noninferiority",
"of",
"fulvestrant",
"could",
"not",
"be",
"demonstrated",
".",
"However",
",",
"in",
"patients",
"with",
"hormone",
"receptor",
"-",
"positive",
"tumors",
",",
"fulvestrant",
"had",
"similar",
"efficacy",
"to",
"tamoxifen",
"and",
"was",
"well",
"tolerated",
"."
] | [
0,
0,
17,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
37,
38,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
37,
38,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
31,
32,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
38 | [
"Long",
"-",
"term",
"survival",
"analysis",
"of",
"addition",
"of",
"carboplatin",
"to",
"neoadjuvant",
"chemotherapy",
"in",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
".",
"Addition",
"of",
"carboplatin",
"(",
"CBDCA",
")",
"to",
"neoadjuvant",
"chemotherapy",
"(",
"NAC",
")",
"in",
"triple",
"-",
"negative",
"breast",
"cancer",
"(",
"TNBC",
")",
"has",
"improved",
"pathological",
"complete",
"response",
"(",
"pCR",
")",
"rates",
"in",
"previous",
"studies",
".",
"We",
"present",
"long",
"-",
"term",
"survival",
"outcomes",
"(",
"disease",
"-",
"free",
"survival",
"[",
"DFS",
"]",
",",
"pre",
"-",
"planned",
"secondary",
"endpoint",
";",
"overall",
"survival",
"[",
"OS",
"]",
",",
"post",
"hoc",
"exploratory",
"endpoint",
")",
"of",
"our",
"randomized",
"study",
"of",
"the",
"addition",
"of",
"CBDCA",
"to",
"NAC",
"for",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
".",
"Patients",
"with",
"stage",
"II",
"/",
"III",
",",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
"(",
"N",
"=",
"179",
")",
"were",
"randomly",
"assigned",
"to",
"receive",
"CP",
"-",
"CEF",
"(",
"four",
"3",
"-week",
"cycles",
"of",
"CBDCA",
"[",
"area",
"under",
"the",
"curve",
",",
"5",
"mg",
"/",
"mL",
"/",
"min",
",",
"day",
"1",
"]",
"and",
"weekly",
"paclitaxel",
"[",
"wPTX",
",",
"80",
"mg",
"/",
"m",
"2",
",",
"day",
"1",
",",
"8",
",",
"15",
"]",
"followed",
"by",
"four",
"3",
"-week",
"cycles",
"of",
"cyclophosphamide",
",",
"epirubicin",
",",
"and",
"5",
"-fluorouracil",
"[",
"CEF",
",",
"500",
"/",
"100",
"/",
"500",
"mg",
"/",
"m",
"2",
"]",
")",
"or",
"P",
"-",
"CEF",
"(",
"four",
"cycles",
"of",
"wPTX",
"followed",
"by",
"four",
"cycles",
"of",
"CEF",
")",
"as",
"NAC",
".",
"DFS",
"and",
"OS",
"were",
"analyzed",
"at",
"each",
"population",
"of",
"pCR",
"status",
"and",
"assigned",
"treatment",
"arm",
".",
"Of",
"179",
"patients",
",",
"154",
"were",
"available",
"for",
"long",
"-",
"term",
"follow",
"-",
"up",
".",
"At",
"a",
"median",
"follow",
"-",
"up",
"of",
"6.6",
"years",
"(",
"range",
",",
"0.7",
"-",
"8.0",
"years",
")",
",",
"patients",
"who",
"achieved",
"pCR",
"[",
"n",
"=",
"42",
",",
"23.5",
"%",
"(",
"CP",
"-",
"CEF",
":",
"n",
"=",
"28",
",",
"P",
"-",
"CEF",
":",
"n",
"=",
"16",
")",
"]",
"had",
"longer",
"DFS",
"and",
"OS",
"than",
"non",
"-",
"pCR",
"patients",
"[",
"DFS",
";",
"HR",
"0.15",
"(",
"0.04",
"-",
"0.61",
")",
",",
"P",
"=",
"0.008",
",",
"OS",
";",
"log",
"-",
"rank",
"P",
"=",
"0.003",
"]",
".",
"Addition",
"of",
"carboplatin",
"to",
"NAC",
"significantly",
"improved",
"DFS",
"and",
"OS",
"in",
"the",
"subset",
"of",
"patients",
"with",
"TNBC",
"[",
"DFS",
":",
"HR",
",",
"0.22",
"(",
"0.06",
"-",
"0.82",
")",
",",
"P",
"=",
"0.015",
";",
"OS",
":",
"HR",
",",
"0.12",
"(",
"0.01",
"-",
"0.96",
")",
",",
"P",
"=",
"0.046",
"]",
",",
"but",
"not",
"in",
"the",
"subset",
"of",
"patients",
"with",
"hormone",
"receptor",
"-",
"positive",
"disease",
"or",
"among",
"all",
"patients",
".",
"Addition",
"of",
"carboplatin",
"to",
"neoadjuvant",
"chemotherapy",
"significantly",
"improved",
"DFS",
"and",
"OS",
"in",
"patients",
"with",
"TNBC",
"but",
"not",
"in",
"those",
"with",
"hormone",
"receptor",
"-",
"positive",
",",
"HER",
"2",
"-",
"negative",
"breast",
"cancer",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
39 | [
"The",
"effect",
"of",
"body",
"mass",
"index",
"on",
"overall",
"and",
"disease",
"-",
"free",
"survival",
"in",
"node",
"-",
"positive",
"breast",
"cancer",
"patients",
"treated",
"with",
"docetaxel",
"and",
"doxorubicin",
"-",
"containing",
"adjuvant",
"chemotherapy",
":",
"the",
"experience",
"of",
"the",
"BIG",
"02",
"-",
"98",
"trial",
".",
"Obesity",
"has",
"been",
"shown",
"to",
"be",
"an",
"indicator",
"of",
"poor",
"prognosis",
"for",
"patients",
"with",
"primary",
"breast",
"cancer",
"(",
"BC",
")",
"regardless",
"of",
"the",
"use",
"of",
"adjuvant",
"systemic",
"therapy",
".",
"This",
"is",
"a",
"retrospective",
"analysis",
"of",
"2",
",",
"887",
"node",
"-",
"positive",
"BC",
"patients",
"enrolled",
"in",
"the",
"BIG",
"02",
"-",
"98",
"adjuvant",
"study",
",",
"a",
"randomised",
"phase",
"III",
"trial",
"whose",
"primary",
"objective",
"was",
"to",
"evaluate",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
"by",
"adding",
"docetaxel",
"to",
"doxorubicin",
"-",
"based",
"chemotherapy",
".",
"In",
"the",
"current",
"analysis",
",",
"the",
"effect",
"of",
"body",
"mass",
"index",
"(",
"BMI",
")",
"on",
"DFS",
"and",
"overall",
"survival",
"(",
"OS",
")",
"was",
"assessed",
".",
"BMI",
"was",
"obtained",
"before",
"the",
"first",
"cycle",
"of",
"chemotherapy",
".",
"Obesity",
"was",
"defined",
"as",
"a",
"BMI",
">",
"or=",
"30",
"kg",
"/",
"m",
"2",
".",
"In",
"total",
",",
"547",
"(",
"19",
"%",
")",
"patients",
"were",
"obese",
"at",
"baseline",
",",
"while",
"2",
",",
"340",
"(",
"81",
"%",
")",
"patients",
"were",
"non",
"-",
"obese",
".",
"Estimated",
"5",
"-year",
"OS",
"was",
"87.5",
"%",
"for",
"non",
"-",
"obese",
"and",
"82.9",
"%",
"for",
"obese",
"patients",
"(",
"HR",
"1.34",
";",
"P",
"=",
"0.013",
")",
".",
"Estimated",
"5",
"-years",
"DFS",
"was",
"75.9",
"%",
"for",
"nonobese",
"and",
"70.0",
"%",
"for",
"obese",
"patients",
"(",
"HR",
"1.20",
";",
"P",
"=",
"0.041",
")",
".",
"Ina",
"multivariate",
"model",
",",
"obesity",
"remained",
"an",
"independent",
"prognostic",
"factor",
"for",
"OS",
"and",
"DFS",
".",
"In",
"this",
"study",
",",
"obesity",
"was",
"associated",
"with",
"poorer",
"outcome",
"in",
"node",
"-",
"positive",
"BC",
"patients",
".",
"Given",
"the",
"increasing",
"prevalence",
"of",
"obesity",
"worldwide",
",",
"more",
"research",
"on",
"improving",
"the",
"treatment",
"of",
"obese",
"BC",
"patients",
"is",
"needed",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
5,
6,
6,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
21,
22,
22,
0,
31,
32,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
31,
32,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
40 | [
"Role",
"of",
"axillary",
"clearance",
"after",
"a",
"tumor",
"-",
"positive",
"sentinel",
"node",
"in",
"the",
"administration",
"of",
"adjuvant",
"therapy",
"in",
"early",
"breast",
"cancer",
".",
"PURPOSE",
"The",
"After",
"Mapping",
"of",
"the",
"Axilla",
":",
"Radiotherapy",
"or",
"Surgery",
"?",
"(",
"AMAROS",
")",
"phase",
"III",
"study",
"compares",
"axillary",
"lymph",
"node",
"dissection",
"(",
"ALND",
")",
"and",
"axillary",
"radiation",
"therapy",
"(",
"ART",
")",
"in",
"early",
"breast",
"cancer",
"patients",
"with",
"tumor",
"-",
"positive",
"sentinel",
"nodes",
".",
"In",
"the",
"ART",
"arm",
",",
"the",
"extent",
"of",
"nodal",
"involvement",
"remains",
"unknown",
",",
"which",
"could",
"have",
"implications",
"on",
"the",
"administration",
"of",
"adjuvant",
"therapy",
".",
"In",
"this",
"preliminary",
"analysis",
",",
"we",
"studied",
"the",
"influence",
"of",
"random",
"assignment",
"to",
"ALND",
"or",
"ART",
"on",
"the",
"choice",
"for",
"adjuvant",
"treatment",
".",
"PATIENTS",
"AND",
"METHODS",
"In",
"the",
"first",
"2",
",",
"000",
"patients",
"enrolled",
"in",
"the",
"AMAROS",
"trial",
",",
"we",
"analyzed",
"the",
"administration",
"of",
"adjuvant",
"systemic",
"therapy",
".",
"Multivariate",
"analysis",
"was",
"used",
"to",
"assess",
"variables",
"affecting",
"the",
"administration",
"of",
"adjuvant",
"chemotherapy",
".",
"Adjuvant",
"therapy",
"was",
"applied",
"according",
"to",
"institutional",
"guidelines",
".",
"Results",
"Of",
"2",
",",
"000",
"patients",
",",
"566",
"patients",
"had",
"a",
"positive",
"sentinel",
"node",
"and",
"were",
"treated",
"per",
"random",
"assignment",
".",
"There",
"was",
"no",
"significant",
"difference",
"in",
"the",
"administration",
"of",
"adjuvant",
"systemic",
"therapy",
".",
"In",
"the",
"ALND",
"and",
"ART",
"arms",
",",
"58",
"%",
"(",
"175",
"of",
"300",
")",
"and",
"61",
"%",
"(",
"162",
"of",
"266",
")",
"of",
"the",
"patients",
",",
"respectively",
",",
"received",
"chemotherapy",
".",
"Endocrine",
"therapy",
"was",
"administered",
"in",
"78",
"%",
"(",
"235",
"of",
"300",
")",
"of",
"the",
"patients",
"in",
"the",
"ALND",
"arm",
"and",
"in",
"76",
"%",
"(",
"203",
"of",
"266",
")",
"of",
"the",
"patients",
"in",
"the",
"ART",
"arm",
".",
"Treatment",
"arm",
"was",
"not",
"a",
"significant",
"factor",
"in",
"the",
"decision",
",",
"and",
"no",
"interactions",
"between",
"treatment",
"arm",
"and",
"other",
"factors",
"were",
"observed",
".",
"Multivariate",
"analysis",
"showed",
"that",
"age",
",",
"tumor",
"grade",
",",
"multifocality",
",",
"and",
"size",
"of",
"the",
"sentinel",
"node",
"metastasis",
"significantly",
"affected",
"the",
"administration",
"of",
"chemotherapy",
".",
"Within",
"the",
"ALND",
"arm",
",",
"the",
"extent",
"of",
"nodal",
"involvement",
"remained",
"not",
"significant",
"in",
"a",
"sensitivity",
"multivariate",
"analysis",
".",
"CONCLUSION",
"Absence",
"of",
"knowledge",
"regarding",
"the",
"extent",
"of",
"nodal",
"involvement",
"in",
"the",
"ART",
"arm",
"appears",
"to",
"have",
"no",
"major",
"impact",
"on",
"the",
"administration",
"of",
"adjuvant",
"therapy",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
18,
18,
18,
0,
19,
20,
20,
20,
20,
20,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
25,
0,
3,
0,
0,
31,
32,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
0,
0,
0,
29,
30,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
41 | [
"[",
"Survival",
"of",
"breast",
"cancer",
"patients",
"treated",
"with",
"inhibitors",
"of",
"the",
"aromatase",
"vs",
"tamoxifen",
"]",
".",
"In",
"Mexico",
"the",
"breast",
"cancer",
"occupies",
"the",
"second",
"place",
"as",
"cause",
"of",
"death",
"by",
"oncological",
"illness",
"and",
"the",
"etiology",
"is",
"considered",
"multifactorial",
".",
"The",
"systemic",
"treatment",
"of",
"this",
"cancer",
"is",
"necessarily",
"after",
"the",
"surgery",
"and",
"simultaneously",
"when",
"radiotherapy",
"is",
"used",
";",
"therefore",
"the",
"recent",
"introduction",
"of",
"newly",
"non",
"toxics",
"and",
"efficient",
"antiestrogens",
"which",
"block",
"the",
"effect",
"of",
"estrogens",
"from",
"circulation",
"have",
"become",
"drugs",
"of",
"first",
"line",
"in",
"the",
"metastasis",
"illness",
".",
"To",
"compare",
"the",
"clinical",
"evolution",
"and",
"the",
"survival",
"of",
"patients",
"with",
"locally",
"advanced",
"breast",
"cancer",
"and",
"metastasis",
"with",
"the",
"use",
"of",
"two",
"therapeutic",
"modalities",
".",
"Under",
"informed",
"consent",
"20",
"patients",
"with",
"diagnosis",
"of",
"breast",
"cancer",
"and",
"out",
"of",
"oncological",
"therapeutic",
"processing",
"were",
"included",
".",
"Randomly",
"an",
"inhibitor",
"of",
"the",
"aromatase",
"(",
"anastrozole",
",",
"1",
"mg",
"for",
"day",
")",
"was",
"used",
"in",
"10",
"patients",
"and",
"in",
"the",
"other",
"10",
"patients",
"tamoxifen",
"(",
"20",
"mg",
"for",
"day",
")",
"both",
"for",
"2",
"years",
",",
"subject",
"to",
"verification",
"of",
"positive",
"estrogens",
"-",
"progesterone",
"receptors",
".",
"Half",
"of",
"the",
"patients",
"of",
"each",
"group",
"had",
"a",
"clinical",
"stage",
"III",
".",
"The",
"most",
"frequent",
"histological",
"diagnosis",
"was",
"the",
"ductal",
"carcinoma",
"in",
"70",
"%",
"of",
"the",
"group",
"with",
"tamoxifen",
"use",
",",
"while",
"in",
"anastrozole",
"group",
"was",
"90",
"%",
";",
"the",
"mastectomy",
"prior",
"to",
"the",
"tamoxifen",
"was",
"carried",
"out",
"in",
"60",
"%",
"of",
"the",
"patients",
"and",
"in",
"50",
"%",
"of",
"the",
"group",
"with",
"anastrozole",
".",
"The",
"acceptable",
"response",
"to",
"the",
"processing",
"in",
"the",
"patients",
"with",
"tamoxifen",
"was",
"complete",
"in",
"the",
"60",
"%",
"of",
"the",
"cases",
",",
"but",
"with",
"the",
"use",
"of",
"anastrozole",
"was",
"80",
"%",
";",
"survival",
"in",
"the",
"group",
"with",
"anastrozole",
"was",
"of",
"100",
"%",
"in",
"two",
"years",
"of",
"follow",
"up",
",",
"while",
"in",
"women",
"that",
"received",
"tamoxifen",
"the",
"survival",
"was",
"90",
"%",
"(",
"p",
"<",
"0.001",
")",
".",
"The",
"use",
"of",
"anastrozole",
"improved",
"the",
"survival",
"as",
"well",
"as",
"the",
"quality",
"of",
"life",
",",
"showing",
"no",
"side",
"effects",
"in",
"this",
"group",
"of",
"patients",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
0,
19,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
21,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
42 | [
"Effects",
"of",
"adjuvant",
"exemestane",
"versus",
"anastrozole",
"on",
"bone",
"mineral",
"density",
"for",
"women",
"with",
"early",
"breast",
"cancer",
"(",
"MA.",
"27",
"B",
")",
":",
"a",
"companion",
"analysis",
"of",
"a",
"randomised",
"controlled",
"trial",
".",
"Treatment",
"of",
"breast",
"cancer",
"with",
"aromatase",
"inhibitors",
"is",
"associated",
"with",
"damage",
"to",
"bones",
".",
"NCIC",
"CTG",
"MA",
".",
"27",
"was",
"an",
"open",
"-",
"label",
",",
"phase",
"3",
",",
"randomised",
"controlled",
"trial",
"in",
"which",
"women",
"with",
"breast",
"cancer",
"were",
"assigned",
"to",
"one",
"of",
"two",
"adjuvant",
"oral",
"aromatase",
"inhibitors",
"-",
"exemestane",
"or",
"anastrozole",
".",
"We",
"postulated",
"that",
"exemestane",
"-",
"a",
"mildly",
"androgenic",
"steroid",
"-",
"might",
"have",
"a",
"less",
"detrimental",
"effect",
"on",
"bone",
"than",
"non",
"-",
"steroidal",
"anastrozole",
".",
"In",
"this",
"companion",
"study",
"to",
"MA",
".",
"27",
",",
"we",
"compared",
"changes",
"in",
"bone",
"mineral",
"density",
"(",
"BMD",
")",
"in",
"the",
"lumbar",
"spine",
"and",
"total",
"hip",
"between",
"patients",
"treated",
"with",
"exemestane",
"and",
"patients",
"treated",
"with",
"anastrozole",
".",
"In",
"MA",
".",
"27",
",",
"postmenopausal",
"women",
"with",
"early",
"stage",
"hormone",
"(",
"oestrogen",
")",
"receptor",
"-",
"positive",
"invasive",
"breast",
"cancer",
"were",
"randomly",
"assigned",
"to",
"exemestane",
"25",
"mg",
"versus",
"anastrozole",
"1",
"mg",
",",
"daily",
".",
"MA.",
"27",
"B",
"recruited",
"two",
"groups",
"of",
"women",
"from",
"MA",
".",
"27",
":",
"those",
"with",
"BMD",
"T",
"-",
"scores",
"of",
"-",
"2",
"·",
"0",
"or",
"more",
"(",
"up",
"to",
"2",
"SDs",
"below",
"sex",
"-",
"matched",
",",
"young",
"adult",
"mean",
")",
"and",
"those",
"with",
"at",
"least",
"one",
"T",
"-",
"score",
"(",
"hip",
"or",
"spine",
")",
"less",
"than",
"-",
"2",
"·",
"0",
".",
"Both",
"groups",
"received",
"vitamin",
"D",
"and",
"calcium",
";",
"those",
"with",
"baseline",
"T",
"-",
"scores",
"of",
"less",
"than",
"-",
"2",
"·",
"0",
"also",
"received",
"bisphosphonates",
".",
"The",
"primary",
"endpoints",
"were",
"percent",
"change",
"of",
"BMD",
"at",
"2",
"years",
"in",
"lumbar",
"spine",
"and",
"total",
"hip",
"for",
"both",
"groups",
".",
"We",
"analysed",
"patients",
"according",
"to",
"which",
"aromatase",
"inhibitor",
"and",
"T",
"-",
"score",
"groups",
"they",
"were",
"allocated",
"to",
"but",
"BMD",
"assessments",
"ceased",
"if",
"patients",
"deviated",
"from",
"protocol",
".",
"This",
"study",
"is",
"registered",
"with",
"ClinicalTrials.gov",
",",
"NCT",
"00354302",
".",
"Between",
"April",
"24",
",",
"2006",
",",
"and",
"May",
"30",
",",
"2008",
",",
"300",
"patients",
"with",
"baseline",
"T",
"-",
"scores",
"of",
"-",
"2",
"·",
"0",
"or",
"more",
"were",
"accrued",
"(",
"147",
"allocated",
"exemestane",
",",
"153",
"anastrozole",
")",
";",
"and",
"197",
"patients",
"with",
"baseline",
"T",
"-",
"scores",
"of",
"less",
"than",
"-",
"2",
"·",
"0",
"(",
"101",
"exemestane",
",",
"96",
"anastrozole",
")",
".",
"For",
"patients",
"with",
"T",
"-",
"scores",
"greater",
"than",
"-",
"2",
"·",
"0",
"at",
"baseline",
",",
"mean",
"change",
"of",
"bone",
"mineral",
"density",
"in",
"the",
"spine",
"at",
"2",
"years",
"did",
"not",
"differ",
"significantly",
"between",
"patients",
"taking",
"exemestane",
"and",
"patients",
"taking",
"anastrozole",
"(",
"-",
"0",
"·",
"92",
"%",
",",
"95",
"%",
"CI",
"-",
"2",
"·",
"35",
"to",
"0",
"·",
"50",
"vs",
"-",
"2",
"·",
"39",
"%",
",",
"95",
"%",
"CI",
"-",
"3",
"·",
"77",
"to",
"-",
"1",
"·",
"01",
";",
"p=",
"0",
"·",
"08",
")",
".",
"Respective",
"mean",
"loss",
"in",
"the",
"hip",
"was",
"-",
"1",
"·",
"93",
"%",
"(",
"95",
"%",
"CI",
"-",
"2",
"·",
"93",
"to",
"-",
"0",
"·",
"93",
")",
"versus",
"-",
"2",
"·",
"71",
"%",
"(",
"95",
"%",
"CI",
"-",
"4",
"·",
"32",
"to",
"-",
"1",
"·",
"11",
";",
"p=",
"0",
"·",
"10",
")",
".",
"Likewise",
"for",
"those",
"who",
"started",
"with",
"T",
"-",
"scores",
"of",
"less",
"than",
"-",
"2",
"·",
"0",
",",
"mean",
"change",
"of",
"spine",
"bone",
"mineral",
"density",
"at",
"2",
"years",
"did",
"not",
"differ",
"significantly",
"between",
"the",
"exemestane",
"and",
"anastrozole",
"treatment",
"groups",
"(",
"2",
"·",
"11",
"%",
",",
"95",
"%",
"CI",
"-",
"0",
"·",
"84",
"to",
"5",
"·",
"06",
"vs",
"3",
"·",
"72",
"%",
",",
"95",
"%",
"CI",
"1",
"·",
"54",
"to",
"5",
"·",
"89",
";",
"p=",
"0",
"·",
"26",
")",
",",
"nor",
"did",
"hip",
"bone",
"mineral",
"density",
"(",
"2",
"·",
"09",
"%",
",",
"95",
"%",
"CI",
"-",
"1",
"·",
"45",
"to",
"5",
"·",
"63",
"vs",
"0",
"·",
"0",
"%",
",",
"95",
"%",
"CI",
"-",
"3",
"·",
"67",
"to",
"3",
"·",
"66",
";",
"p=",
"0",
"·",
"28",
")",
".",
"Patients",
"with",
"baseline",
"T",
"-",
"score",
"of",
"-",
"2",
"·",
"0",
"or",
"more",
"taking",
"exemestane",
"had",
"two",
"fragility",
"fractures",
"and",
"two",
"other",
"fractures",
",",
"those",
"taking",
"anastrozole",
"had",
"three",
"fragility",
"fractures",
"and",
"five",
"other",
"fractures",
".",
"For",
"patients",
"who",
"had",
"baseline",
"T",
"-",
"scores",
"of",
"less",
"than",
"-",
"2",
"·",
"0",
"taking",
"exemestane",
",",
"one",
"had",
"a",
"fragility",
"fracture",
"and",
"four",
"had",
"other",
"fractures",
",",
"whereas",
"those",
"taking",
"anastrozole",
"had",
"five",
"fragility",
"fractures",
"and",
"one",
"other",
"fracture",
".",
"Our",
"results",
"demonstrate",
"that",
"adjuvant",
"treatment",
"with",
"aromatase",
"inhibitors",
"can",
"be",
"considered",
"for",
"breast",
"cancer",
"patients",
"who",
"have",
"T",
"-",
"scores",
"less",
"than",
"-",
"2",
"·",
"0",
".",
"Canadian",
"Cancer",
"Society",
"Research",
"Institute",
",",
"Pfizer",
",",
"Canadian",
"Institutes",
"of",
"Health",
"Research",
"."
] | [
0,
0,
0,
17,
0,
19,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
5,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
34,
34,
34,
34,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
36,
36,
36,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
33,
34,
34,
34,
34,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
36,
36,
36,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
34,
34,
34,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
36,
36,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
33,
34,
34,
34,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
36,
36,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
21,
22,
0,
25,
21,
22,
0,
0,
0,
0,
0,
27,
21,
22,
0,
27,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
21,
22,
0,
25,
0,
21,
22,
0,
0,
0,
0,
0,
0,
27,
21,
22,
0,
27,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
43 | [
"Effectiveness",
"of",
"early",
"physiotherapy",
"to",
"prevent",
"lymphoedema",
"after",
"surgery",
"for",
"breast",
"cancer",
":",
"randomised",
",",
"single",
"blinded",
",",
"clinical",
"trial",
".",
"To",
"determine",
"the",
"effectiveness",
"of",
"early",
"physiotherapy",
"in",
"reducing",
"the",
"risk",
"of",
"secondary",
"lymphoedema",
"after",
"surgery",
"for",
"breast",
"cancer",
".",
"Randomised",
",",
"single",
"blinded",
",",
"clinical",
"trial",
".",
"University",
"hospital",
"in",
"Alcalá",
"de",
"Henares",
",",
"Madrid",
",",
"Spain",
".",
"120",
"women",
"who",
"had",
"breast",
"surgery",
"involving",
"dissection",
"of",
"axillary",
"lymph",
"nodes",
"between",
"May",
"2005",
"and",
"June",
"2007",
".",
"The",
"early",
"physiotherapy",
"group",
"was",
"treated",
"by",
"a",
"physiotherapist",
"with",
"a",
"physiotherapy",
"programme",
"including",
"manual",
"lymph",
"drainage",
",",
"massage",
"of",
"scar",
"tissue",
",",
"and",
"progressive",
"active",
"and",
"action",
"assisted",
"shoulder",
"exercises",
".",
"This",
"group",
"also",
"received",
"an",
"educational",
"strategy",
".",
"The",
"control",
"group",
"received",
"the",
"educational",
"strategy",
"only",
".",
"Incidence",
"of",
"clinically",
"significant",
"secondary",
"lymphoedema",
"(",
">",
"2",
"cm",
"increase",
"in",
"arm",
"circumference",
"measured",
"at",
"two",
"adjacent",
"points",
"compared",
"with",
"the",
"non",
"-",
"affected",
"arm",
")",
".",
"116",
"women",
"completed",
"the",
"one",
"year",
"follow",
"-",
"up",
".",
"Of",
"these",
",",
"18",
"developed",
"secondary",
"lymphoedema",
"(",
"16",
"%",
")",
":",
"14",
"in",
"the",
"control",
"group",
"(",
"25",
"%",
")",
"and",
"four",
"in",
"the",
"intervention",
"group",
"(",
"7",
"%",
")",
".",
"The",
"difference",
"was",
"significant",
"(",
"P=",
"0.01",
")",
";",
"risk",
"ratio",
"0.28",
"(",
"95",
"%",
"confidence",
"interval",
"0.10",
"to",
"0.79",
")",
".",
"A",
"survival",
"analysis",
"showed",
"a",
"significant",
"difference",
",",
"with",
"secondary",
"lymphoedema",
"being",
"diagnosed",
"four",
"times",
"earlier",
"in",
"the",
"control",
"group",
"than",
"in",
"the",
"intervention",
"group",
"(",
"intervention",
"/",
"control",
",",
"hazard",
"ratio",
"0.26",
",",
"95",
"%",
"confidence",
"interval",
"0.09",
"to",
"0.79",
")",
".",
"Early",
"physiotherapy",
"could",
"be",
"an",
"effective",
"intervention",
"in",
"the",
"prevention",
"of",
"secondary",
"lymphoedema",
"in",
"women",
"for",
"at",
"least",
"one",
"year",
"after",
"surgery",
"for",
"breast",
"cancer",
"involving",
"dissection",
"of",
"axillary",
"lymph",
"nodes",
".",
"Current",
"controlled",
"trials",
"ISRCTN",
"95870846",
"."
] | [
0,
0,
0,
17,
0,
0,
13,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
16,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
31,
32,
0,
0,
25,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
44 | [
"Effectiveness",
"of",
"OK-",
"432",
"(",
"Sapylin",
")",
"to",
"reduce",
"seroma",
"formation",
"after",
"axillary",
"lymphadenectomy",
"for",
"breast",
"cancer",
".",
"The",
"occurrence",
"of",
"seroma",
"formation",
"after",
"axillary",
"lymphadenectomy",
"for",
"breast",
"cancer",
"can",
"not",
"be",
"ignored",
".",
"Various",
"approaches",
"have",
"been",
"used",
"in",
"an",
"effort",
"to",
"reduce",
"it",
",",
"but",
"these",
"results",
"are",
"still",
"controversial",
".",
"We",
"aimed",
"to",
"describe",
"a",
"new",
"method",
"of",
"application",
"of",
"OK-",
"432",
"(",
"Sapylin",
",",
"heat",
"-",
"treated",
"Su",
"strain",
"of",
"Streptococcus",
")",
"to",
"reduce",
"seroma",
"formation",
"after",
"axillary",
"lymphadenectomy",
"for",
"breast",
"cancer",
"and",
"to",
"verify",
"the",
"safety",
"and",
"efficacy",
"of",
"it",
"as",
"a",
"beneficial",
"supplement",
"for",
"conventional",
"surgery",
".",
"A",
"prospective",
",",
"randomized",
"analysis",
"of",
"consecutive",
"quadrantectomy",
"or",
"mastectomy",
"plus",
"axillary",
"lymphadenectomy",
"using",
"or",
"not",
"using",
"OK-",
"432",
"was",
"designed",
".",
"From",
"July",
"2010",
"to",
"November",
"2011",
",",
"a",
"total",
"of",
"111",
"patients",
"were",
"enrolled",
"in",
"this",
"prospective",
",",
"randomized",
"study",
"and",
"completed",
"the",
"follow",
"-",
"up",
".",
"OK-",
"432",
"applied",
"to",
"the",
"axillary",
"fossa",
"plus",
"placement",
"of",
"closed",
"suction",
"drainage",
"was",
"used",
"in",
"54",
"patients",
"(",
"the",
"experimental",
"group",
")",
";",
"placement",
"of",
"closed",
"suction",
"drainage",
"was",
"used",
"in",
"57",
"patients",
"(",
"the",
"control",
"group",
")",
".",
"There",
"were",
"no",
"statistical",
"significance",
"between",
"the",
"two",
"groups",
"in",
"terms",
"of",
"age",
",",
"body",
"mass",
"index",
",",
"treatment",
"received",
",",
"tumor",
"size",
",",
"number",
"of",
"removed",
"lymph",
"nodes",
",",
"and",
"lymph",
"node",
"status",
".",
"Postoperative",
"drainage",
"magnitude",
"and",
"duration",
"were",
"significantly",
"reduced",
"in",
"the",
"experimental",
"group",
"(",
"P",
"=",
"0.008",
"and",
"0.003",
",",
"respectively",
")",
".",
"One",
"week",
"after",
"hospital",
"discharge",
",",
"fewer",
"patients",
"developed",
"a",
"palpable",
"seroma",
"in",
"the",
"experimental",
"group",
":",
"10",
"in",
"the",
"experimental",
"group",
"versus",
"28",
"in",
"the",
"control",
"group",
"(",
"P",
"=",
"0.001",
")",
".",
"Fewer",
"seromas",
"needed",
"aspiration",
"(",
"mean",
"1",
"[",
"range",
"0",
"-",
"3",
"]",
"in",
"the",
"experimental",
"group",
"vs.",
"mean",
"4",
"[",
"range",
"1",
"-",
"5",
"]",
"in",
"the",
"control",
"group",
";",
"P",
"<",
"0.001",
")",
".",
"There",
"were",
"no",
"significant",
"differences",
"in",
"terms",
"of",
"the",
"incidence",
"of",
"complications",
"associated",
"with",
"axillary",
"lymphadenectomy",
"(",
"P",
"=",
"0.941",
")",
".",
"OK-",
"432",
"is",
"a",
"feasible",
"and",
"safe",
"option",
"for",
"axillary",
"lymphadenectomy",
"for",
"breast",
"cancer",
".",
"The",
"use",
"of",
"it",
"does",
"not",
"always",
"prevent",
"seroma",
"formation",
",",
"but",
"it",
"can",
"reduce",
"drainage",
"magnitude",
"and",
"duration",
",",
"as",
"well",
"as",
"decrease",
"the",
"incidence",
"of",
"seroma",
"after",
"the",
"removal",
"of",
"drainage",
".",
"It",
"may",
"be",
"increasingly",
"conducted",
"in",
"day",
"surgery",
"clinics",
"."
] | [
0,
0,
17,
18,
18,
18,
18,
0,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
33,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
45 | [
"A",
"text",
"message",
"intervention",
"to",
"support",
"women",
"'s",
"physical",
"and",
"mental",
"health",
"after",
"breast",
"cancer",
"treatments",
"(",
"EMPOWER",
"-",
"SMS",
")",
":",
"a",
"randomised",
"controlled",
"trial",
"protocol",
".",
"Breast",
"cancer",
"is",
"the",
"most",
"common",
"cancer",
"diagnosed",
"in",
"women",
"worldwide",
".",
"In",
"developed",
"countries",
",",
"80",
"-",
"90",
"%",
"of",
"women",
"will",
"survive",
"five",
"years",
"after",
"diagnosis",
"but",
"the",
"transition",
"from",
"hospital",
"-",
"based",
"care",
"to",
"health",
"self",
"-",
"management",
"and",
"self",
"-",
"efficacy",
"can",
"be",
"difficult",
".",
"Text",
"messaging",
"programs",
"offer",
"a",
"simple",
"and",
"proven",
"way",
"to",
"provide",
"support",
"to",
"people",
"with",
"chronic",
"diseases",
".",
"This",
"study",
"aims",
"to",
"test",
"the",
"effectiveness",
"of",
"a",
"text",
"message",
"support",
"program",
"at",
"improving",
"women",
"'s",
"health",
"self",
"-",
"efficacy",
",",
"and",
"physical",
"and",
"mental",
"health",
"outcomes",
"after",
"breast",
"cancer",
"treatments",
"compared",
"to",
"usual",
"care",
"at",
"6",
"-months",
"and",
"to",
"understand",
"the",
"barriers",
"and",
"enablers",
"to",
"widespread",
"implementation",
".",
"Single",
"-",
"blind",
"randomised",
"control",
"trial",
"(",
"RCT",
";",
"N",
"=",
"160",
")",
"comparing",
"a",
"text",
"message",
"support",
"intervention",
"to",
"usual",
"care",
"in",
"women",
"with",
"breast",
"cancer",
"(",
"recruited",
"from",
"a",
"large",
"tertiary",
"referral",
"hospital",
"in",
"Sydney",
",",
"Australia",
")",
".",
"The",
"intervention",
"group",
"will",
"receive",
"a",
"six",
"-",
"month",
"text",
"message",
"support",
"program",
",",
"which",
"consists",
"of",
"semi",
"-",
"personalised",
",",
"supportive",
",",
"lifestyle",
"-",
"focused",
"text",
"messages",
"(",
"4",
"messages",
"/",
"week",
")",
"in",
"addition",
"to",
"usual",
"care",
".",
"The",
"control",
"group",
"will",
"receive",
"usual",
"care",
"without",
"the",
"text",
"message",
"program",
".",
"Outcomes",
"will",
"be",
"assessed",
"at",
"6",
"-months",
".",
"The",
"primary",
"outcome",
"is",
"change",
"in",
"self",
"-",
"efficacy",
"for",
"managing",
"chronic",
"disease",
".",
"Secondary",
"outcomes",
"include",
"change",
"in",
"clinical",
"outcomes",
"(",
"body",
"mass",
"index",
")",
",",
"lifestyle",
"outcomes",
"(",
"physical",
"activity",
"levels",
",",
"dietary",
"behaviours",
")",
",",
"mood",
"(",
"depression",
"and",
"anxiety",
"scales",
")",
",",
"quality",
"of",
"life",
",",
"satisfaction",
"with",
",",
"and",
"usefulness",
"of",
"the",
"intervention",
".",
"Analyses",
"will",
"be",
"performed",
"on",
"the",
"principle",
"of",
"intention",
"-",
"to",
"-",
"treat",
"to",
"examine",
"differences",
"between",
"intervention",
"and",
"control",
"groups",
".",
"This",
"study",
"will",
"test",
"if",
"a",
"scalable",
"and",
"cost",
"-",
"effective",
"text",
"-",
"messaging",
"intervention",
"is",
"effective",
"at",
"improving",
"women",
"'s",
"health",
"self",
"-",
"efficacy",
",",
"as",
"well",
"as",
"physical",
"and",
"mental",
"health",
"outcomes",
".",
"Moreover",
",",
"this",
"study",
"will",
"provide",
"essential",
"preliminary",
"data",
"to",
"bolster",
"a",
"large",
"multicentre",
"RCT",
"to",
"helpsupport",
"breast",
"cancer",
"survivors",
"throughout",
"recovery",
"and",
"beyond",
".",
"Australia",
"New",
"Zealand",
"Clinical",
"Trials",
"Registry",
"(",
"ANZCTR",
")",
"number",
"ACTRN",
"12618002020268",
",",
"17",
"December",
"2018",
"."
] | [
0,
17,
18,
18,
0,
0,
0,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
16,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
0,
23,
24,
0,
0,
23,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
46 | [
"Serum",
"lipids",
",",
"lipoproteins",
",",
"and",
"risk",
"of",
"breast",
"cancer",
":",
"a",
"nested",
"case",
"-",
"control",
"study",
"using",
"multiple",
"time",
"points",
".",
"There",
"is",
"strong",
"evidence",
"that",
"breast",
"cancer",
"risk",
"is",
"influenced",
"by",
"environmental",
"factors",
".",
"Blood",
"lipid",
"and",
"lipoprotein",
"levels",
"are",
"also",
"influenced",
"by",
"environmental",
"factors",
"and",
"are",
"associated",
"with",
"some",
"breast",
"cancer",
"risk",
"factors",
".",
"We",
"examined",
"whether",
"serial",
"measures",
"of",
"serum",
"lipids",
"and",
"lipoproteins",
"were",
"associated",
"with",
"breast",
"cancer",
"risk",
".",
"We",
"carried",
"out",
"a",
"nested",
"case",
"-",
"control",
"study",
"within",
"a",
"randomized",
"long",
"-",
"term",
"dietary",
"intervention",
"trial",
"with",
"4690",
"women",
"with",
"extensive",
"mammographic",
"density",
"followed",
"for",
"an",
"average",
"of",
"10",
"years",
"for",
"breast",
"cancer",
"incidence",
".",
"We",
"measured",
"lipids",
"in",
"an",
"average",
"of",
"4.2",
"blood",
"samples",
"for",
"279",
"invasive",
"breast",
"cancer",
"case",
"subjects",
"and",
"558",
"matched",
"control",
"subjects",
".",
"We",
"calculated",
"subaverages",
"of",
"lipids",
"for",
"each",
"subject",
"based",
"on",
"menopausal",
"status",
"and",
"use",
"of",
"hormone",
"replacement",
"therapy",
"(",
"HRT",
")",
"at",
"blood",
"collection",
"and",
"analyzed",
"their",
"association",
"with",
"breast",
"cancer",
"using",
"generalized",
"estimating",
"equations",
".",
"All",
"statistical",
"tests",
"were",
"two",
"-",
"sided",
".",
"High",
"-",
"density",
"lipoprotein",
"-",
"cholesterol",
"(",
"HDL",
"-",
"C",
")",
"(",
"P",
"=",
".",
"05",
")",
"and",
"apoA",
"1",
"(",
"P",
"=",
".",
"02",
")",
"levels",
"were",
"positively",
"associated",
"with",
"breast",
"cancer",
"risk",
"(",
"75",
"(",
"th",
")",
"vs",
"25",
"(",
"th",
")",
"percentile",
":",
"HDL",
"-",
"C",
",",
"23",
"%",
"higher",
";",
"apoA",
"1",
",",
"28",
"%",
"higher",
")",
"and",
"non",
"-",
"HDL",
"-",
"C",
"(",
"P",
"=",
".",
"03",
")",
"and",
"apoB",
"(",
"P",
"=",
".",
"01",
")",
"levels",
"were",
"negatively",
"associated",
"(",
"75",
"(",
"th",
")",
"vs",
"25",
"(",
"th",
")",
"percentile",
":",
"non",
"-",
"HDL",
"-",
"C",
",",
"19",
"%",
"lower",
";",
"apoB",
",",
"22",
"%",
"lower",
")",
".",
"These",
"associations",
"were",
"observed",
"only",
"when",
"lipids",
"were",
"measured",
"when",
"HRT",
"was",
"not",
"used",
".",
"Total",
"cholesterol",
"and",
"triglyceride",
"levels",
"were",
"not",
"statistically",
"significantly",
"associated",
"with",
"breast",
"cancer",
"risk",
".",
"These",
"results",
"demonstrate",
"that",
"serum",
"lipids",
"are",
"associated",
"with",
"breast",
"cancer",
"risk",
"in",
"women",
"with",
"extensive",
"mammographic",
"density",
".",
"The",
"possibility",
"that",
"interventions",
"for",
"heart",
"disease",
"prevention",
",",
"which",
"aim",
"to",
"reduce",
"non",
"-",
"HDL",
"-",
"C",
"or",
"raise",
"HDL",
"-",
"C",
",",
"may",
"have",
"effects",
"on",
"breast",
"cancer",
"risk",
"merits",
"examination",
"."
] | [
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
47 | [
"Letrozole",
"and",
"palbociclib",
"versus",
"chemotherapy",
"as",
"neoadjuvant",
"therapy",
"of",
"high",
"-",
"risk",
"luminal",
"breast",
"cancer",
".",
"Palbociclib",
"is",
"a",
"CDK",
"4",
"/",
"6",
"inhibitor",
"with",
"demonstrated",
"efficacy",
"and",
"safety",
"in",
"combination",
"with",
"endocrine",
"therapy",
"in",
"advanced",
"luminal",
"breast",
"cancer",
"(",
"LBC",
")",
".",
"We",
"evaluated",
"the",
"respective",
"efficacy",
"and",
"safety",
"of",
"chemotherapy",
"and",
"letrozole",
"-",
"palbociclib",
"(",
"LETPAL",
")",
"combination",
"as",
"neoadjuvant",
"treatment",
"in",
"patients",
"with",
"high",
"-",
"risk",
"LBC",
".",
"NeoPAL",
"(",
"UCBG",
"10",
"/",
"4",
",",
"NCT",
"02400567",
")",
"is",
"a",
"randomised",
",",
"parallel",
",",
"non",
"-",
"comparative",
"phase",
"II",
"study",
".",
"Patients",
"with",
"ER",
"-",
"positive",
",",
"HER",
"2",
"-",
"negative",
",",
"Prosigna",
"®",
"-defined",
"luminal",
"B",
",",
"or",
"luminal",
"A",
"and",
"node",
"-",
"positive",
",",
"stage",
"II",
"-",
"III",
"breast",
"cancer",
",",
"not",
"candidate",
"for",
"breast",
"-",
"conserving",
"surgery",
",",
"were",
"randomly",
"assigned",
"to",
"either",
"letrozole",
"(",
"2.5",
"mg",
"daily",
")",
"and",
"palbociclib",
"(",
"125",
"mg",
"daily",
",",
"3",
"weeks",
"/",
"4",
")",
"during",
"19",
"weeks",
",",
"or",
"to",
"FEC",
"100",
"(",
"5",
"FU",
"500",
"mg",
"/",
"m",
"2",
",",
"epirubicin",
"100",
"mg",
"/",
"m",
"2",
",",
"cyclophosphamide",
"500",
"mg",
"/",
"m",
"2",
")",
"×",
"3",
"21",
"-day",
"courses",
"followed",
"by",
"docetaxel",
"100",
"mg",
"/",
"m",
"2",
"×",
"3",
"21",
"-day",
"courses",
".",
"Primary",
"end",
"point",
"was",
"residual",
"cancer",
"burden",
"(",
"RCB",
"0",
"-I",
"rate",
")",
".",
"Secondary",
"end",
"points",
"included",
"clinical",
"response",
",",
"proliferation",
"-",
"based",
"markers",
",",
"and",
"safety",
".",
"Overall",
",",
"106",
"patients",
"were",
"randomised",
"[",
"median",
"Prosigna",
"®",
"ROR",
"Score",
"71",
"(",
"22",
"-",
"93",
")",
"]",
".",
"RCB",
"0",
"-I",
"was",
"observed",
"in",
"four",
"and",
"eight",
"patients",
"in",
"LETPAL",
"[",
"7.7",
"%",
"(",
"95",
"%",
"CI",
"0.4",
"-",
"14.9",
")",
"]",
"and",
"chemotherapy",
"[",
"15.7",
"%",
"(",
"95",
"%",
"CI",
"5.7",
"-",
"25.7",
")",
"]",
"arms",
",",
"respectively",
".",
"Pathological",
"complete",
"response",
"rates",
"were",
"3.8",
"%",
"and",
"5.9",
"%",
".",
"Clinical",
"response",
"(",
"75",
"%",
")",
"and",
"breast",
"-",
"conserving",
"surgery",
"rates",
"(",
"69",
"%",
")",
"were",
"similar",
"in",
"both",
"arms",
".",
"Preoperative",
"Endocrine",
"Prognostic",
"Index",
"0",
"scores",
"(",
"breast",
"cancer",
"-",
"specific",
"survival",
")",
"were",
"observed",
"in",
"17.6",
"%",
"and",
"8.0",
"%",
"of",
"patients",
"in",
"LETPAL",
"and",
"chemotherapy",
"arms",
",",
"respectively",
".",
"Safety",
"profile",
"was",
"as",
"expected",
",",
"with",
"2",
"versus",
"17",
"serious",
"adverse",
"events",
"(",
"including",
"11",
"grade",
"4",
"serious",
"AEs",
"in",
"the",
"chemotherapy",
"arm",
")",
".",
"LETPAL",
"combination",
"was",
"associated",
"with",
"poor",
"pathological",
"response",
"but",
"encouraging",
"clinical",
"and",
"biomarker",
"responses",
"in",
"Prosigna",
"®",
"-defined",
"high",
"-",
"risk",
"LBC",
".",
"Contemporary",
"chemotherapy",
"regimen",
"was",
"associated",
"with",
"poor",
"pathological",
"and",
"biomarker",
"responses",
",",
"with",
"a",
"much",
"less",
"favourable",
"safety",
"profile",
".",
"LETPAL",
"combination",
"might",
"represent",
"an",
"alternative",
"to",
"chemotherapy",
"in",
"early",
"high",
"-",
"risk",
"LBC",
".",
"NCT",
"02400567",
"."
] | [
17,
18,
18,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
23,
24,
0,
23,
24,
24,
24,
0,
0,
23,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
25,
0,
27,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
21,
22,
0,
29,
30,
0,
0,
21,
22,
22,
22,
22,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
27,
21,
22,
22,
0,
0,
27,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
48 | [
"Effect",
"of",
"different",
"doses",
"of",
"metformin",
"on",
"serum",
"testosterone",
"and",
"insulin",
"in",
"non",
"-",
"diabetic",
"women",
"with",
"breast",
"cancer",
":",
"a",
"randomized",
"study",
".",
"This",
"is",
"a",
"randomized",
"controlled",
"trial",
"to",
"test",
"the",
"effect",
"of",
"different",
"doses",
"of",
"metformin",
"in",
"patients",
"with",
"breast",
"cancer",
"and",
"without",
"diabetes",
",",
"with",
"the",
"aim",
"of",
"modifying",
"the",
"hormonal",
"and",
"metabolic",
"parameters",
"linked",
"to",
"breast",
"cancer",
"prognosis",
".",
"Analysis",
"of",
"the",
"results",
"suggest",
"that",
"the",
"dose",
"of",
"1500",
"mg",
"/",
"d",
"of",
"metformin",
"causes",
"a",
"significant",
"reduction",
"of",
"insulin",
"and",
"testosterone",
"serum",
"levels",
".",
"Serum",
"levels",
"of",
"insulin",
"and",
"testosterone",
"may",
"affect",
"both",
"breast",
"cancer",
"(",
"BC",
")",
"incidence",
"and",
"prognosis",
".",
"Metformin",
"reduces",
"hyperglycemia",
"and",
"insulin",
"levels",
"in",
"patients",
"with",
"diabetes",
".",
"In",
"women",
"without",
"diabetes",
"and",
"with",
"polycystic",
"ovary",
"syndrome",
",",
"metformin",
"lowers",
"both",
"insulin",
"and",
"testosterone",
"levels",
".",
"Patients",
"with",
"diabetes",
"who",
"are",
"treated",
"with",
"metformin",
"showed",
"a",
"lower",
"risk",
"of",
"cancer",
";",
"a",
"protective",
"effect",
"of",
"metformin",
"also",
"was",
"observed",
"for",
"BC",
".",
"Recently",
",",
"studies",
"on",
"metformin",
"use",
"for",
"prevention",
"or",
"treatment",
"of",
"BC",
"have",
"been",
"proposed",
"in",
"patients",
"who",
"are",
"not",
"diabetic",
".",
"The",
"aim",
"of",
"the",
"present",
"study",
"was",
"to",
"test",
"the",
"effect",
"of",
"different",
"doses",
"of",
"metformin",
"on",
"serum",
"levels",
"of",
"insulin",
"and",
"testosterone",
"in",
"those",
"postmenopausal",
"patients",
"with",
"breast",
"cancer",
"and",
"without",
"diabetes",
"who",
"have",
"basal",
"testosterone",
"levels",
"≥",
"0.28",
"ng",
"/",
"mL",
"(",
"median",
"value",
")",
".",
"A",
"total",
"of",
"125",
"eligible",
"women",
"were",
"initially",
"invited",
"to",
"take",
"metformin",
"500",
"mg",
"/",
"d",
"for",
"3",
"months",
".",
"The",
"108",
"women",
"who",
"completed",
"the",
"first",
"3",
"months",
"were",
"invited",
"to",
"continue",
"the",
"study",
"with",
"metformin",
"1000",
"mg",
"/",
"d",
"(",
"500",
"mg",
"twice",
"a",
"day",
"[",
"b.i.d",
".",
"]",
")",
"for",
"1",
"month",
".",
"The",
"women",
"were",
"then",
"randomized",
"into",
"2",
"groups",
",",
"and",
",",
"for",
"the",
"subsequent",
"5",
"months",
",",
"1",
"group",
"increased",
"the",
"dose",
"by",
"taking",
"metformin",
"1500",
"mg",
"/",
"d",
"(",
"500",
"mg",
"3",
"times",
"a",
"day",
"[",
"t.i.d",
".",
"]",
")",
",",
"and",
"the",
"other",
"group",
"continued",
"with",
"metformin",
"1000",
"mg",
"/d",
"(",
"500",
"[",
"b.i.d",
".",
"]",
")",
".",
"A",
"total",
"of",
"96",
"women",
"completed",
"the",
"study",
":",
"43",
"women",
"received",
"1500",
"mg",
"/",
"d",
",",
"and",
"53",
"women",
"received",
"1000",
"mg",
"/",
"d.",
"The",
"women",
"who",
"took",
"1500",
"mg",
"/",
"d",
"showed",
"a",
"significant",
"reduction",
"of",
"insulin",
"level",
",",
"HOMA",
"-",
"IR",
"index",
"(",
"homeostasis",
"model",
"assessment",
"-",
"insulin",
"resistance",
"index",
")",
",",
"testosterone",
"level",
",",
"and",
"free",
"androgen",
"index",
"compared",
"with",
"women",
"treated",
"with",
"1000",
"mg",
"/",
"d.",
"After",
"treatment",
"with",
"1500",
"mg",
"/",
"d",
",",
"the",
"insulin",
"level",
"decreased",
"by",
"25",
"%",
"and",
"the",
"testosterone",
"level",
"decreased",
"by",
"23",
"%",
".",
"Both",
"these",
"changes",
"might",
"have",
"a",
"prognostic",
"importance",
"."
] | [
0,
0,
0,
0,
0,
17,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
49 | [
"Breast",
"cancer",
"incidence",
"in",
"the",
"randomized",
"PEARL",
"trial",
"of",
"lasofoxifene",
"in",
"postmenopausal",
"osteoporotic",
"women",
".",
"Currently",
"available",
"selective",
"estrogen",
"receptor",
"modulators",
"reduce",
"the",
"risk",
"of",
"breast",
"cancer",
",",
"but",
"they",
"are",
"not",
"widely",
"used",
".",
"In",
"the",
"Postmenopausal",
"Evaluation",
"and",
"Risk",
"-",
"Reduction",
"with",
"Lasofoxifene",
"(",
"PEARL",
")",
"trial",
",",
"lasofoxifene",
"was",
"shown",
"to",
"reduce",
"the",
"risk",
"of",
"estrogen",
"receptor",
"-",
"positive",
"(",
"ER+",
")",
"breast",
"cancer",
",",
"nonvertebral",
"and",
"vertebral",
"fractures",
",",
"coronary",
"artery",
"disease",
",",
"and",
"stroke",
",",
"but",
"the",
"effects",
"on",
"total",
"breast",
"cancer",
"(",
"invasive",
"and",
"ductal",
"carcinoma",
"in",
"situ",
",",
"ER+",
"and",
"estrogen",
"receptor",
"-",
"negative",
"[",
"ER-",
"]",
")",
"and",
"ER+",
"invasive",
"breast",
"cancer",
"are",
"unknown",
".",
"Postmenopausal",
"women",
"(",
"n",
"=",
"8556",
")",
"aged",
"59",
"-",
"80",
"years",
"with",
"low",
"bone",
"density",
"and",
"normal",
"mammograms",
"were",
"randomly",
"assigned",
"to",
"two",
"doses",
"of",
"lasofoxifene",
"(",
"0.25",
"and",
"0.5",
"mg",
")",
"or",
"placebo",
".",
"The",
"primary",
"endpoints",
"of",
"the",
"PEARL",
"trial",
"were",
"incidence",
"of",
"ER+",
"breast",
"cancer",
"and",
"nonvertebral",
"fractures",
"at",
"5",
"years",
".",
"A",
"nested",
"case",
"-",
"control",
"study",
"of",
"49",
"incident",
"breast",
"cancer",
"case",
"patients",
"and",
"156",
"unaffected",
"control",
"subjects",
"from",
"the",
"PEARL",
"trial",
"was",
"performed",
"to",
"evaluate",
"treatment",
"effects",
"on",
"risk",
"of",
"total",
"and",
"ER+",
"invasive",
"breast",
"cancer",
"by",
"baseline",
"serum",
"estradiol",
"and",
"sex",
"hormone",
"-",
"binding",
"globulin",
"levels",
"using",
"logistic",
"regression",
"models",
".",
"Cox",
"proportional",
"hazards",
"models",
"were",
"used",
"to",
"evaluate",
"risk",
"of",
"total",
"breast",
"cancer",
"and",
"ER+",
"invasive",
"breast",
"cancer",
"using",
"intention",
"-",
"to",
"-",
"treat",
"analysis",
".",
"All",
"statistical",
"tests",
"were",
"two",
"-",
"sided",
".",
"Breast",
"cancer",
"was",
"confirmed",
"in",
"49",
"women",
".",
"Compared",
"with",
"placebo",
",",
"0.5",
"mg",
"of",
"lasofoxifene",
"statistically",
"significantly",
"reduced",
"the",
"risk",
"of",
"total",
"breast",
"cancer",
"by",
"79",
"%",
"(",
"hazard",
"ratio",
"=",
"0.21",
";",
"95",
"%",
"confidence",
"interval",
"[",
"CI",
"]",
"=",
"0.08",
"to",
"0.55",
")",
"and",
"ER+",
"invasive",
"breast",
"cancer",
"by",
"83",
"%",
"(",
"hazard",
"ratio",
"=",
"0.17",
";",
"95",
"%",
"CI",
"=",
"0.05",
"to",
"0.57",
")",
".",
"The",
"effects",
"of",
"0.5",
"mg",
"of",
"lasofoxifene",
"on",
"total",
"breast",
"cancer",
"were",
"similar",
"regardless",
"of",
"Gail",
"score",
",",
"whereas",
"the",
"effects",
"were",
"markedly",
"stronger",
"for",
"women",
"with",
"baseline",
"estradiol",
"levels",
"greater",
"than",
"the",
"median",
"(",
"odds",
"ratio",
"=",
"0.11",
";",
"95",
"%",
"CI",
"=",
"0.02",
"to",
"0.51",
")",
"vs",
"those",
"with",
"levels",
"less",
"than",
"the",
"median",
"(",
"odds",
"ratio",
"=",
"0.78",
";",
"95",
"%",
"CI",
"=",
"0.16",
"to",
"3.79",
";",
"P",
"(",
"interaction",
")",
"=",
".",
"04",
")",
".",
"A",
"0.5",
"-mg",
"dose",
"of",
"lasofoxifene",
"appears",
"to",
"reduce",
"the",
"risks",
"of",
"both",
"total",
"and",
"ER+",
"invasive",
"breast",
"cancer",
"in",
"postmenopausal",
"women",
"with",
"osteoporosis",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
9,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
7,
8,
8,
8,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
50 | [
"Focused",
"microwave",
"thermotherapy",
"for",
"preoperative",
"treatment",
"of",
"invasive",
"breast",
"cancer",
":",
"a",
"review",
"of",
"clinical",
"studies",
".",
"Preoperative",
"focused",
"microwave",
"thermotherapy",
"(",
"FMT",
")",
"is",
"a",
"promising",
"method",
"for",
"targeted",
"treatment",
"of",
"breast",
"cancer",
"cells",
".",
"Results",
"of",
"four",
"multi",
"-",
"institutional",
"clinical",
"studies",
"of",
"preoperative",
"FMT",
"for",
"treating",
"invasive",
"carcinomas",
"in",
"the",
"intact",
"breast",
"are",
"reviewed",
".",
"Externally",
"applied",
"wide",
"-",
"field",
"adaptive",
"phased",
"-",
"array",
"FMT",
"has",
"been",
"investigated",
"both",
"as",
"a",
"preoperative",
"heat",
"-",
"alone",
"ablation",
"treatment",
"and",
"as",
"a",
"combination",
"treatment",
"with",
"preoperative",
"anthracycline",
"-",
"based",
"chemotherapy",
"for",
"breast",
"tumors",
"ranging",
"in",
"ultrasound",
"-",
"measured",
"size",
"from",
"0.8",
"to",
"7.8",
"cm",
".",
"In",
"phase",
"I",
",",
"eight",
"of",
"ten",
"(",
"80",
"%",
")",
"patients",
"receiving",
"a",
"single",
"low",
"dose",
"of",
"FMT",
"prior",
"to",
"receiving",
"mastectomy",
"had",
"a",
"partial",
"tumor",
"response",
"quantified",
"by",
"either",
"ultrasound",
"measurements",
"of",
"tumor",
"volume",
"reduction",
"or",
"by",
"pathologic",
"cell",
"kill",
".",
"In",
"phase",
"II",
",",
"the",
"FMT",
"thermal",
"dose",
"was",
"increased",
"to",
"establish",
"a",
"threshold",
"dose",
"to",
"induce",
"100",
"%",
"pathologic",
"tumor",
"cell",
"kill",
"for",
"invasive",
"carcinomas",
"prior",
"to",
"breast",
"-",
"conserving",
"surgery",
"(",
"BCS",
")",
".",
"In",
"a",
"randomized",
"study",
"for",
"patients",
"with",
"early",
"-",
"stage",
"invasive",
"breast",
"cancer",
",",
"of",
"those",
"patients",
"receiving",
"preoperative",
"FMT",
"at",
"ablative",
"temperatures",
",",
"0",
"of",
"34",
"(",
"0",
"%",
")",
"patients",
"had",
"positive",
"tumor",
"margins",
",",
"whereas",
"positive",
"margins",
"occurred",
"in",
"4",
"of",
"41",
"(",
"9.8",
"%",
")",
"of",
"patients",
"receiving",
"BCS",
"alone",
"(",
"P",
"=",
"0.13",
")",
".",
"In",
"a",
"randomized",
"study",
"for",
"patients",
"with",
"large",
"tumors",
",",
"based",
"on",
"ultrasound",
"measurements",
"the",
"median",
"tumor",
"volume",
"reduction",
"was",
"88.4",
"%",
"(",
"n",
"=",
"14",
")",
"for",
"patients",
"receiving",
"FMT",
"and",
"neoadjuvant",
"chemotherapy",
",",
"compared",
"with",
"58.8",
"%",
"(",
"n",
"=",
"10",
")",
"reduction",
"in",
"the",
"neoadjuvant",
"chemotherapy",
"-",
"alone",
"arm",
"(",
"P",
"=",
"0.048",
")",
".",
"Wide",
"-",
"field",
"adaptive",
"phased",
"-",
"array",
"FMT",
"can",
"be",
"safely",
"administered",
"in",
"a",
"preoperative",
"setting",
",",
"and",
"data",
"from",
"randomized",
"studies",
"suggest",
"both",
"a",
"reduction",
"in",
"positive",
"tumor",
"margins",
"as",
"a",
"heat",
"-",
"alone",
"treatment",
"for",
"early",
"-",
"stage",
"breast",
"cancer",
"and",
"a",
"reduction",
"in",
"tumor",
"volume",
"when",
"used",
"in",
"combination",
"with",
"anthracycline",
"-",
"based",
"chemotherapy",
"for",
"patients",
"with",
"large",
"breast",
"cancer",
"tumors",
".",
"Larger",
"randomized",
"studies",
"are",
"required",
"to",
"verify",
"these",
"conclusions",
"."
] | [
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
29,
30,
0,
0,
0,
21,
22,
22,
0,
0,
21,
22,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
0,
0,
29,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
51 | [
"Preventive",
"effect",
"of",
"oral",
"magnesium",
"in",
"postmastectomy",
"pain",
":",
"protocol",
"for",
"a",
"randomised",
",",
"double",
"-",
"blind",
",",
"controlled",
"clinical",
"trial",
".",
"Breast",
"cancer",
"affects",
"1",
"in",
"10",
"women",
"worldwide",
",",
"and",
"mastectomy",
"is",
"a",
"cause",
"of",
"chronic",
"pain",
"with",
"neuropathic",
"characteristics",
".",
"N",
"-",
"methyl",
"-",
"D",
"-",
"aspartate",
"receptor",
"(",
"NMDAR",
")",
"antagonists",
"such",
"as",
"ketamine",
",",
"memantine",
",",
"dextromethorphan",
"or",
"magnesium",
"are",
"used",
"to",
"treat",
"refractory",
"pain",
"by",
"blocking",
"NMDAR",
".",
"Oral",
"memantine",
"has",
"been",
"shown",
"to",
"prevent",
"postmastectomy",
"pain",
"and",
"cognitive",
"impact",
"and",
"to",
"maintain",
"quality",
"of",
"life",
".",
"Likewise",
",",
"the",
"present",
"study",
"is",
"intended",
"to",
"assess",
"the",
"preventive",
"effect",
"of",
"oral",
"magnesium",
",",
"administered",
"ahead",
"of",
"mastectomy",
",",
"on",
"the",
"development",
"of",
"neuropathic",
"pain",
".",
"As",
"a",
"physiological",
"blocker",
"of",
"NMDAR",
",",
"magnesium",
"could",
"be",
"an",
"interesting",
"candidate",
"to",
"prevent",
"postoperative",
"pain",
"and",
"associated",
"comorbidities",
",",
"including",
"cognitive",
"and",
"emotional",
"disorders",
",",
"multiple",
"analgesic",
"consumption",
"and",
"impaired",
"quality",
"of",
"life",
".",
"A",
"randomised",
"double",
"-",
"blind",
"controlled",
"clinical",
"trial",
"(",
"NCT",
"03063931",
")",
"will",
"include",
"100",
"women",
"with",
"breast",
"cancer",
"undergoing",
"mastectomy",
"at",
"the",
"Oncology",
"Hospital",
",",
"Clermont",
"-",
"Ferrand",
",",
"France",
".",
"Magnesium",
"(",
"100",
"mg",
"/",
"day",
";",
"n=",
"50",
")",
"or",
"placebo",
"(",
"n=",
"50",
")",
"will",
"be",
"administered",
"for",
"6",
"weeks",
",",
"starting",
"2",
"weeks",
"before",
"surgery",
".",
"Intensity",
"of",
"pain",
",",
"cognitive",
"and",
"emotional",
"function",
"and",
"quality",
"of",
"life",
"will",
"be",
"assessed",
"by",
"questionnaires",
".",
"The",
"primary",
"endpoint",
"is",
"pain",
"intensity",
"on",
"a",
"0",
"-",
"10",
"numerical",
"rating",
"scale",
"at",
"1",
"month",
"postmastectomy",
".",
"Data",
"analysis",
"will",
"use",
"mixed",
"models",
";",
"all",
"tests",
"will",
"be",
"two",
"-",
"tailed",
",",
"with",
"type",
"-",
"I",
"error",
"set",
"at",
"α=",
"0.05",
".",
"The",
"study",
"protocol",
"and",
"informed",
"consent",
"form",
"were",
"approved",
"in",
"December",
"2016",
"by",
"the",
"French",
"Research",
"Ethics",
"Committee",
"(",
"South",
"East",
"VI",
"Committee",
")",
".",
"Results",
"will",
"be",
"communicated",
"in",
"various",
"congresses",
"and",
"published",
"in",
"international",
"publications",
".",
"NCT",
"03063931",
"."
] | [
0,
0,
0,
17,
18,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
19,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
52 | [
"No",
"effect",
"of",
"exercise",
"on",
"insulin",
"-",
"like",
"growth",
"factor",
"-",
"I",
",",
"insulin",
",",
"and",
"glucose",
"in",
"young",
"women",
"participating",
"in",
"a",
"16",
"-week",
"randomized",
"controlled",
"trial",
".",
"Insulin",
"-",
"like",
"growth",
"factor",
"I",
"(",
"IGF",
"-",
"I",
")",
"and",
"IGF",
"binding",
"protein",
"3",
"(",
"IGFBP-",
"3",
")",
"have",
"been",
"associated",
"with",
"increased",
"risk",
"of",
"breast",
"cancer",
".",
"We",
"report",
"our",
"findings",
"on",
"the",
"effects",
"of",
"16",
"weeks",
"of",
"aerobic",
"exercise",
"on",
"IGF",
"axis",
"proteins",
",",
"insulin",
",",
"glucose",
",",
"and",
"insulin",
"resistance",
"of",
"319",
"young",
"sedentary",
"women",
".",
"Demographics",
",",
"health",
"surveys",
",",
"body",
"composition",
",",
"dietary",
"intake",
",",
"and",
"blood",
"samples",
"were",
"collected",
"at",
"baseline",
"and",
"16",
"weeks",
".",
"IGF",
"-",
"I",
"and",
"IGFBP-",
"1",
",",
"IGFBP-",
"2",
",",
"and",
"IGFBP-",
"3",
"were",
"measured",
"by",
"ELISA",
".",
"Exercise",
"adherence",
"was",
"88",
"%",
".",
"The",
"dropout",
"rates",
"for",
"the",
"exercise",
"and",
"control",
"groups",
"were",
"21.7",
"%",
"and",
"14.5",
"%",
",",
"respectively",
".",
"There",
"was",
"a",
"small",
"significant",
"change",
"from",
"baseline",
"in",
"IGFBP-",
"3",
"concentrations",
".",
"IGFBP-",
"3",
"levels",
"decreased",
"in",
"controls",
"and",
"increased",
"in",
"exercisers",
".",
"The",
"between",
"-",
"group",
"difference",
"was",
"significant",
".",
"No",
"other",
"changes",
"were",
"noted",
".",
"Sixteen",
"weeks",
"of",
"exercise",
"had",
"minimum",
"or",
"no",
"effect",
"on",
"IGF",
"proteins",
"of",
"young",
"women",
".",
"Our",
"study",
"supports",
"findings",
"from",
"previous",
"studies",
"conducted",
"in",
"older",
"populations",
"and",
"raises",
"the",
"question",
"of",
"what",
"type",
"of",
"intervention",
"is",
"needed",
"to",
"change",
"circulating",
"levels",
"of",
"IGF",
"proteins",
"in",
"humans",
"."
] | [
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
19,
20,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
53 | [
"Histopathological",
"assessment",
"of",
"anastrozole",
"and",
"tamoxifen",
"as",
"preoperative",
"(",
"neoadjuvant",
")",
"treatment",
"in",
"postmenopausal",
"Japanese",
"women",
"with",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
"in",
"the",
"PROACT",
"trial",
".",
"The",
"PReOperative",
"'",
"Arimidex",
"'",
"Compared",
"with",
"Tamoxifen",
"(",
"PROACT",
")",
"trial",
"compared",
"neoadjuvant",
"anastrozole",
"and",
"tamoxifen",
"in",
"postmenopausal",
"women",
"with",
"large",
",",
"operable",
"or",
"potentially",
"operable",
",",
"locally",
"advanced",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
".",
"Here",
",",
"we",
"compare",
"objective",
"clinical",
"responses",
"with",
"histopathological",
"tumor",
"responses",
"to",
"therapy",
"in",
"a",
"cohort",
"of",
"97",
"Japanese",
"patients",
",",
"in",
"order",
"to",
"investigate",
"the",
"consistency",
"of",
"assessment",
"methods",
"and",
"the",
"change",
"in",
"estrogen",
"-",
"receptor",
"(",
"ER",
")",
"and",
"progesterone",
"-",
"receptor",
"(",
"PgR",
")",
"status",
".",
"Histopathological",
"response",
"and",
"the",
"change",
"in",
"ER",
"and",
"PgR",
"status",
"were",
"assessed",
"by",
"comparing",
"pathological",
"specimens",
"collected",
"at",
"baseline",
"(",
"via",
"needle",
"biopsy",
")",
"with",
"those",
"collected",
"at",
"3",
"months",
"(",
"from",
"excised",
"tumors",
")",
".",
"The",
"response",
"was",
"evaluated",
"using",
"Pathological",
"Response",
"Criteria",
"for",
"Breast",
"Cancer",
"as",
"defined",
"by",
"the",
"Japanese",
"Breast",
"Cancer",
"Society",
".",
"The",
"patients",
"were",
"randomized",
"to",
"receive",
"anastrozole",
"(",
"n",
"=",
"48",
")",
"or",
"tamoxifen",
"(",
"n",
"=",
"49",
")",
".",
"A",
"numerically",
"greater",
"histopathological",
"response",
"rate",
"was",
"observed",
"when",
"neoadjuvant",
"anastrozole",
"compared",
"with",
"neoadjuvant",
"tamoxifen",
"(",
"35.4",
"and",
"12.2",
"%",
",",
"respectively",
")",
".",
"The",
"histopathological",
"and",
"clinical",
"objective",
"response",
"rates",
"agreed",
"in",
"63",
"/",
"97",
"patients",
".",
"The",
"ER",
"status",
"of",
"5",
"/",
"40",
"patients",
"changed",
"from",
"positive",
"at",
"baseline",
"to",
"negative",
"at",
"3",
"months",
"in",
"the",
"anastrozole",
"group",
"compared",
"with",
"20",
"/",
"37",
"patients",
"in",
"the",
"tamoxifen",
"group",
".",
"The",
"PgR",
"status",
"of",
"16",
"/",
"17",
"patients",
"in",
"the",
"anastrozole",
"group",
"and",
"of",
"1",
"/",
"11",
"patients",
"in",
"the",
"tamoxifen",
"group",
"changed",
"from",
"positive",
"to",
"negative",
".",
"These",
"data",
"support",
"the",
"findings",
"of",
"the",
"main",
"PROACT",
"trial",
",",
"which",
"confirmed",
"that",
"anastrozole",
",",
"as",
"compared",
"with",
"tamoxifen",
",",
"is",
"an",
"effective",
"neoadjuvant",
"endocrine",
"treatment",
"in",
"objective",
"response",
"rates",
"for",
"postmenopausal",
"women",
"with",
"large",
"operable",
"hormone",
"-",
"receptor",
"positive",
"breast",
"cancer",
".",
"Further",
"follow",
"-",
"up",
"is",
"required",
"to",
"confirm",
"whether",
"histopathological",
"responses",
"to",
"therapy",
"correlate",
"with",
"an",
"overall",
"improvement",
"in",
"survival",
"."
] | [
0,
0,
0,
17,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
0,
31,
32,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
25,
0,
3,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
54 | [
"Axillary",
"node",
"sampling",
"in",
"conjunction",
"with",
"sentinel",
"node",
"biopsy",
"in",
"patients",
"with",
"breast",
"cancer",
".",
"A",
"prospective",
"preliminary",
"study",
".",
"In",
"patients",
"with",
"breast",
"cancer",
"(",
"BC",
")",
",",
"axillary",
"lymph",
"node",
"sampling",
"(",
"ALNS",
")",
"is",
"a",
"reliable",
"procedure",
"with",
"low",
"morbidity",
",",
"alternative",
"or",
"complementary",
"to",
"sentinel",
"lymph",
"node",
"biopsy",
"(",
"SLNB",
")",
",",
"which",
"may",
"improve",
"the",
"detection",
"rate",
"of",
"axillary",
"node",
"metastases",
"as",
"compared",
"to",
"SLNB",
"alone",
"in",
"staging",
"the",
"axilla",
".",
"The",
"aim",
"of",
"this",
"study",
"was",
"to",
"assess",
"the",
"usefulness",
"of",
"ALNS",
"in",
"conjunction",
"with",
"SLNB",
"in",
"improving",
"the",
"sensitivity",
"of",
"SLNB",
"alone",
"at",
"frozen",
"section",
"examination",
".",
"One",
"hundred",
"and",
"twelve",
"women",
"(",
"median",
"age",
"56",
"years",
",",
"range",
"29",
"-",
"71",
"years",
")",
"with",
"BC",
"underwent",
"SLNB",
"using",
"a",
"combined",
"radioisotope",
"and",
"isosulfan",
"blue",
"dye",
"technique",
".",
"Two",
"groups",
"of",
"age-",
"and",
"tumor",
"size",
"-",
"matched",
"patients",
"were",
"prospectively",
"randomized",
":",
"Group",
"A",
"(",
"SLNB",
"alone",
",",
"55",
"women",
")",
"and",
"group",
"B",
"(",
"SLNB",
"plus",
"ALNS",
",",
"57",
"women",
")",
".",
"Intraoperative",
"examination",
"showed",
"SN",
"involvement",
"in",
"32",
"(",
"28.6",
"%",
")",
"patients",
":",
"group",
"A",
"=",
"14",
"(",
"25.5",
"%",
")",
",",
"group",
"B",
"=",
"18",
"(",
"31.6",
"%",
")",
",",
"whilst",
"the",
"final",
"pathology",
"showed",
"axillary",
"node",
"involvement",
"in",
"7",
"further",
"cases",
"(",
"group",
"A",
"=",
"5",
",",
"group",
"B",
"=",
"2",
")",
".",
"The",
"sensitivity",
"and",
"accuracy",
"were",
"73.7",
"%",
"vs.",
"90.0",
"%",
"(",
"p",
"=",
"0.23",
")",
"and",
"90.9",
"%",
"vs.",
"94.7",
"%",
"(",
"p",
"=",
"0.49",
")",
",",
"group",
"A",
"vs.",
"B",
",",
"respectively",
".",
"Multivariate",
"analysis",
"showed",
"that",
"age",
">",
"65",
"years",
"and",
"body",
"mass",
"index",
"independently",
"correlated",
"with",
"the",
"amount",
"of",
"axillary",
"drainage",
"in",
"both",
"groups",
",",
"which",
"was",
"47.5",
"±",
"11.3",
"and",
"49.6",
"±",
"12.2",
"ml",
"(",
"A",
"vs.",
"B",
",",
"p",
"=",
"NS",
")",
",",
"respectively",
".",
"In",
"conclusion",
",",
"in",
"our",
"preliminary",
"study",
",",
"ALNS",
"in",
"conjunction",
"with",
"SLNB",
"is",
"a",
"low",
"-",
"risk",
"procedure",
",",
"useful",
"to",
"reduce",
"the",
"false",
"-",
"negative",
"rate",
"of",
"SLNB",
"and",
"to",
"improve",
"the",
"accuracy",
"of",
"intraoperative",
"evaluation",
"of",
"the",
"axillary",
"nodes",
"in",
"patients",
"with",
"BC",
"."
] | [
17,
18,
18,
18,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
0,
0,
0,
0,
7,
8,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
31,
32,
0,
0,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
25,
0,
0,
0,
21,
0,
21,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
35,
0,
43,
0,
33,
0,
41,
42,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
55 | [
"Preoperative",
"MRI",
"of",
"the",
"breast",
"(",
"POMB",
")",
"influences",
"primary",
"treatment",
"in",
"breast",
"cancer",
":",
"a",
"prospective",
",",
"randomized",
",",
"multicenter",
"study",
".",
"Breast",
"magnetic",
"resonance",
"imaging",
"(",
"MRI",
")",
"has",
"shown",
"high",
"sensitivity",
"in",
"determining",
"tumor",
"extent",
",",
"multifocality",
",",
"and",
"occult",
"contralateral",
"breast",
"cancer",
".",
"Low",
"specificity",
",",
"unnecessary",
"mastectomies",
",",
"and",
"costs",
"are",
"arguments",
"against",
"MRI",
".",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"determine",
"whether",
"preoperative",
"breast",
"MRI",
"would",
"affect",
"primary",
"surgical",
"management",
",",
"reduce",
"reexcision",
"/",
"reoperation",
"procedures",
",",
"and",
"influence",
"the",
"choice",
"of",
"neoadjuvant",
"treatment",
"in",
"patients",
"with",
"newly",
"diagnosed",
"breast",
"cancer",
".",
"This",
"prospective",
",",
"randomized",
",",
"multicenter",
"study",
"included",
"440",
"breast",
"cancer",
"patients",
"younger",
"than",
"aged",
"56",
"years",
"from",
"three",
",",
"Swedish",
",",
"large",
"-",
"volume",
"breast",
"units",
".",
"Patients",
"were",
"randomly",
"allocated",
"on",
"a",
"1",
":1",
"basis",
"to",
"either",
"preoperative",
"staging",
"with",
"breast",
"MRI",
"(",
"n",
"=",
"220",
")",
"or",
"no",
"breast",
"MRI",
"(",
"n",
"=",
"220",
")",
"(",
"control",
"group",
")",
".",
"Treatment",
"planning",
"of",
"all",
"patients",
"was",
"discussed",
"at",
"multidisciplinary",
"team",
"conferences",
".",
"In",
"patients",
"randomized",
"to",
"the",
"MRI",
"group",
",",
"who",
"had",
"an",
"observed",
"higher",
"percentage",
"of",
"planned",
"breast",
"-",
"conserving",
"surgery",
"(",
"BCS",
")",
"compared",
"with",
"the",
"control",
"group",
",",
"a",
"change",
"from",
"suggested",
"breast",
"conservation",
"to",
"mastectomy",
"occurred",
"in",
"23",
"of",
"153",
"(",
"15",
"%",
")",
"patients",
".",
"Breast",
"MRI",
"provided",
"additional",
"information",
"in",
"83",
"of",
"220",
"(",
"38",
"%",
")",
"patients",
",",
"which",
"caused",
"a",
"change",
"in",
"treatment",
"plan",
"in",
"40",
"(",
"18",
"%",
")",
".",
"The",
"breast",
"reoperation",
"rate",
"was",
"significantly",
"lower",
"in",
"the",
"MRI",
"group",
":",
"11",
"of",
"220",
"(",
"5",
"%",
")",
"versus",
"33",
"of",
"220",
"(",
"15",
"%",
")",
"in",
"the",
"control",
"group",
"(",
"p",
"<",
"0.001",
")",
".",
"The",
"number",
"of",
"mastectomies",
",",
"axillary",
"reoperations",
",",
"and",
"the",
"number",
"of",
"patients",
"receiving",
"neoadjuvant",
"chemotherapy",
"after",
"definitive",
"treatment",
"did",
"not",
"differ",
"significantly",
"between",
"the",
"groups",
".",
"Preoperative",
"staging",
"with",
"breast",
"MRI",
"in",
"women",
"younger",
"than",
"age",
"56",
"years",
"altered",
"the",
"treatment",
"plan",
"in",
"18",
"%",
"of",
"the",
"patients",
".",
"Although",
"a",
"higher",
"MRI",
"-",
"related",
"conversion",
"rate",
"from",
"breast",
"conservation",
"to",
"mastectomy",
"was",
"found",
",",
"the",
"final",
"numbers",
"of",
"mastectomies",
"did",
"not",
"differ",
"between",
"the",
"two",
"groups",
".",
"The",
"breast",
"reoperation",
"rate",
"in",
"the",
"MRI",
"group",
"was",
"significantly",
"reduced",
"."
] | [
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
7,
8,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
19,
20,
20,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
25,
0,
3,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
25,
0,
29,
30,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
29,
30,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
22,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
56 | [
"Palbociclib",
":",
"A",
"Novel",
"Cyclin",
"-",
"Dependent",
"Kinase",
"Inhibitor",
"for",
"Hormone",
"Receptor",
"-",
"Positive",
"Advanced",
"Breast",
"Cancer",
".",
"To",
"review",
"palbociclib",
",",
"a",
"novel",
"small",
"-",
"molecule",
"inhibitor",
"of",
"cyclin",
"-",
"dependent",
"kinases",
"4",
"and",
"6",
",",
"and",
"its",
"current",
"place",
"in",
"therapy",
"for",
"the",
"treatment",
"of",
"hormone",
"receptor",
"(",
"HMR",
")",
"-positive",
",",
"human",
"epidermal",
"growth",
"factor",
"receptor",
"2",
"(",
"Her",
"2",
")",
"-negative",
"advanced",
"breast",
"cancer",
".",
"Four",
"phase",
"I",
"trials",
",",
"2",
"phase",
"II",
"trials",
",",
"and",
"1",
"phase",
"III",
"trial",
"were",
"identified",
"from",
"May",
"2004",
"to",
"May",
"2015",
"using",
"PubMed",
",",
"American",
"Society",
"of",
"Clinical",
"Oncology",
"(",
"ASCO",
")",
"abstracts",
",",
"and",
"European",
"Society",
"of",
"Medical",
"Oncology",
"(",
"ESMO",
")",
"abstracts",
".",
"In",
"the",
"first",
"-",
"line",
"setting",
",",
"the",
"phase",
"II",
"PALbociclib",
":",
"Ongoing",
"trials",
"in",
"the",
"Management",
"of",
"breast",
"cAncer",
"(",
"PALOMA",
")",
"-",
"1",
"trial",
"randomized",
"patients",
"to",
"receive",
"letrozole",
"alone",
"or",
"letrozole",
"plus",
"palbociclib",
"125",
"mg",
"daily",
"for",
"3",
"weeks",
",",
"followed",
"by",
"1",
"week",
"off",
",",
"as",
"initial",
"therapy",
"for",
"advanced",
"breast",
"cancer",
".",
"The",
"investigator",
"-",
"assessed",
"median",
"progression",
"-",
"free",
"survival",
"(",
"PFS",
")",
"was",
"20.2",
"months",
"for",
"the",
"combination",
"versus",
"10.2",
"months",
"for",
"letrozole",
"alone",
"(",
"hazard",
"ratio",
"[",
"HR",
"]",
"=",
"0.488",
";",
"95",
"%",
"CI",
"=",
"0.319",
"-",
"0.748",
";",
"1",
"-sided",
"P",
"=",
"0.0004",
")",
".",
"The",
"ensuing",
"Food",
"and",
"Drug",
"Administration",
"approval",
"of",
"palbociclib",
"was",
"given",
"a",
"\"",
"breakthrough",
"therapy",
"\"",
"designation",
",",
"where",
"preliminary",
"evidence",
"suggests",
"substantial",
"improvement",
"over",
"existing",
"therapies",
"for",
"a",
"serious",
"or",
"life",
"-",
"threatening",
"disease",
".",
"A",
"confirmatory",
"phase",
"III",
"trial",
",",
"PALOMA-",
"2",
",",
"is",
"under",
"way",
".",
"In",
"patients",
"who",
"were",
"previously",
"treated",
"with",
"endocrine",
"therapy",
"for",
"advanced",
"breast",
"cancer",
",",
"the",
"phase",
"III",
"PALOMA-",
"3",
"trial",
"randomized",
"patients",
"to",
"fulvestrant",
"plus",
"palbociclib",
"versus",
"fulvestrant",
"plus",
"placebo",
".",
"The",
"investigator",
"-",
"assessed",
"median",
"PFS",
"at",
"the",
"time",
"of",
"a",
"preplanned",
"analysis",
"was",
"9.2",
"months",
"with",
"palbociclib",
"-",
"fulvestrant",
"compared",
"with",
"3.8",
"months",
"with",
"placebo",
"-",
"fulvestrant",
"(",
"HR",
"=",
"0.42",
";",
"95",
"%",
"CI",
"=",
"0.32",
"-",
"0.56",
";",
"P",
"<",
"0.001",
")",
".",
"Palbociclib",
",",
"the",
"first",
"-",
"in",
"-",
"class",
"CDK",
"4",
"/",
"6",
"inhibitor",
",",
"significantly",
"extended",
"PFS",
"in",
"combination",
"with",
"endocrine",
"therapy",
"in",
"the",
"first",
"and",
"subsequent",
"lines",
"of",
"treatment",
"for",
"HMR",
"-",
"positive",
",",
"Her",
"2",
"-",
"negative",
"advanced",
"breast",
"cancer",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
37,
38,
0,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
0,
37,
38,
0,
0,
0,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
57 | [
"Vasomotor",
"symptoms",
",",
"adoption",
"of",
"a",
"low",
"-",
"fat",
"dietary",
"pattern",
",",
"and",
"risk",
"of",
"invasive",
"breast",
"cancer",
":",
"a",
"secondary",
"analysis",
"of",
"the",
"Women",
"'s",
"Health",
"Initiative",
"randomized",
"controlled",
"dietary",
"modification",
"trial",
".",
"To",
"assess",
"whether",
"the",
"effect",
"of",
"a",
"low",
"-",
"fat",
"dietary",
"pattern",
"on",
"breast",
"cancer",
"incidence",
"varied",
"by",
"report",
"of",
"baseline",
"vasomotor",
"symptoms",
".",
"Postmenopausal",
"women",
"age",
"50",
"to",
"79",
"years",
"enrolled",
"onto",
"the",
"Women",
"'s",
"Health",
"Initiative",
"(",
"WHI",
")",
"Dietary",
"Modification",
"trial",
"from",
"1993",
"to",
"1998",
"were",
"randomly",
"assigned",
"to",
"a",
"low",
"-",
"fat",
"dietary",
"intervention",
"(",
"n",
"=",
"19",
",",
"541",
")",
"or",
"comparison",
"(",
"n",
"=",
"29",
",",
"294",
")",
".",
"Presence",
"of",
"vasomotor",
"symptoms",
"at",
"baseline",
"was",
"ascertained",
"from",
"a",
"34",
"-item",
"self",
"-",
"report",
"symptom",
"inventory",
".",
"Women",
"were",
"queried",
"semi",
"-",
"annually",
"for",
"a",
"new",
"diagnosis",
"of",
"breast",
"cancer",
".",
"Each",
"case",
"report",
"was",
"verified",
"by",
"medical",
"record",
"and",
"pathology",
"report",
"review",
"by",
"centrally",
"trained",
"WHI",
"physician",
"adjudicators",
".",
"Among",
"participants",
"who",
"reported",
"hot",
"flashes",
"(",
"HFs",
")",
"at",
"baseline",
"(",
"n",
"=",
"3",
",",
"375",
")",
",",
"those",
"assigned",
"to",
"the",
"low",
"-",
"fat",
"diet",
"had",
"a",
"breast",
"cancer",
"rate",
"of",
"0.27",
"compared",
"with",
"their",
"counterparts",
"in",
"the",
"control",
"group",
"who",
"had",
"a",
"rate",
"of",
"0.41",
"(",
"hazard",
"ratio",
"[",
"HR",
"]",
"=",
"0.65",
";",
"95",
"%",
"CI",
",",
"0.42",
"to",
"1.01",
")",
".",
"Among",
"women",
"reporting",
"no",
"HFs",
"(",
"n",
"=",
"45",
",",
"160",
")",
",",
"the",
"breast",
"cancer",
"rate",
"was",
"0.42",
"in",
"those",
"assigned",
"to",
"the",
"low",
"-",
"fat",
"diet",
"compared",
"with",
"0.46",
"in",
"the",
"control",
"group",
"(",
"HR",
"=",
"0.93",
";",
"95",
"%",
"CI",
",",
"0.84",
"to",
"1.03",
";",
"P",
"for",
"interaction",
"=",
".",
"12",
"by",
"HF",
"status",
")",
".",
"Furthermore",
",",
"the",
"dietary",
"benefits",
"observed",
"seemed",
"to",
"be",
"specific",
"to",
"estrogen",
"receptor",
"(",
"ER",
")",
"-positive",
"/",
"progesterone",
"receptor",
"(",
"PR",
")",
"-positive",
"tumors",
"(",
"ER",
"positive",
"/",
"PR",
"positive",
"v",
"other",
",",
"P",
"for",
"risk",
"=",
".",
"03",
")",
".",
"Although",
"women",
"with",
"and",
"without",
"HFs",
"differed",
"with",
"regard",
"to",
"breast",
"cancer",
"risk",
"factors",
",",
"the",
"effect",
"of",
"the",
"diet",
"intervention",
"on",
"breast",
"cancer",
"incidence",
"by",
"HF",
"status",
"was",
"consistent",
"across",
"risk",
"factor",
"strata",
".",
"The",
"results",
"of",
"this",
"trial",
",",
"which",
"are",
"hypothesis",
"generating",
",",
"suggest",
"that",
"HFs",
"may",
"identify",
"a",
"subgroup",
"of",
"postmenopausal",
"women",
"whose",
"risk",
"of",
"invasive",
"breast",
"cancer",
"might",
"be",
"reduced",
"with",
"the",
"adoption",
"of",
"a",
"low",
"-",
"fat",
"eating",
"pattern",
"."
] | [
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
4,
4,
0,
0,
19,
0,
0,
0,
5,
6,
6,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
31,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
58 | [
"Five",
"-",
"year",
"outcome",
"for",
"women",
"randomised",
"in",
"a",
"phase",
"III",
"trial",
"comparing",
"doxorubicin",
"and",
"cyclophosphamide",
"with",
"doxorubicin",
"and",
"docetaxel",
"as",
"primary",
"medical",
"therapy",
"in",
"early",
"breast",
"cancer",
":",
"an",
"Anglo",
"-",
"Celtic",
"Cooperative",
"Oncology",
"Group",
"study",
".",
"To",
"compare",
"the",
"long",
"-",
"term",
"outcome",
"of",
"women",
"with",
"primary",
"or",
"locally",
"advanced",
"breast",
"cancer",
"randomised",
"to",
"receive",
"either",
"doxorubicin",
"and",
"cyclophosphamide",
"(",
"AC",
")",
"or",
"doxorubicin",
"and",
"docetaxel",
"(",
"AD",
")",
"as",
"primary",
"chemotherapy",
".",
"Eligible",
"patients",
"with",
"histologic",
"-",
"proven",
"breast",
"cancer",
"with",
"primary",
"tumours",
">",
"or",
"=",
"3",
"cm",
",",
"inflammatory",
"or",
"locally",
"advanced",
"disease",
",",
"and",
"no",
"evidence",
"of",
"distant",
"metastases",
",",
"were",
"randomised",
"to",
"receive",
"a",
"maximum",
"of",
"6",
"cycles",
"of",
"either",
"doxorubicin",
"(",
"60",
"mg",
"/",
"m",
"(",
"2",
")",
")",
"plus",
"cyclophosphamide",
"(",
"600",
"mg",
"/",
"m",
"(",
"2",
")",
")",
"i",
"/",
"v",
"or",
"doxorubicin",
"(",
"50",
"mg",
"/",
"m",
"(",
"2",
")",
")",
"plus",
"docetaxel",
"(",
"75",
"mg",
"/",
"m",
"(",
"2",
")",
")",
"i",
"/",
"v",
"every",
"3",
"weeks",
",",
"followed",
"by",
"surgery",
"on",
"completion",
"of",
"chemotherapy",
".",
"Clinical",
"and",
"pathologic",
"responses",
"have",
"previously",
"been",
"reported",
".",
"Time",
"to",
"relapse",
",",
"site",
"of",
"relapse",
",",
"and",
"all",
"-",
"cause",
"mortality",
"were",
"recorded",
".",
"This",
"updated",
"analysis",
"compares",
"long",
"-",
"term",
"disease",
"-",
"free",
"(",
"DFS",
")",
"and",
"overall",
"survival",
"(",
"OS",
")",
"using",
"stratified",
"log",
"rank",
"methods",
".",
"A",
"total",
"of",
"363",
"patients",
"were",
"randomised",
"to",
"AC",
"(",
"n",
"=",
"181",
")",
"or",
"AD",
"(",
"n",
"=",
"182",
")",
".",
"A",
"complete",
"pathologic",
"response",
"was",
"observed",
"in",
"16",
"%",
"for",
"AC",
"and",
"12",
"%",
"for",
"AD",
"(",
"P",
"=",
"0.43",
")",
".",
"The",
"number",
"of",
"patients",
"with",
"positive",
"axillary",
"nodes",
"at",
"surgery",
"with",
"AC",
"was",
"61",
"%",
"and",
"AD",
"66",
"%",
"(",
"P",
"=",
"0.36",
")",
".",
"At",
"a",
"median",
"follow",
"-",
"up",
"of",
"99",
"months",
"there",
"is",
"no",
"significant",
"difference",
"between",
"the",
"two",
"groups",
"for",
"DFS",
"(",
"P",
"=",
"0.20",
")",
"and",
"OS",
"(",
"P",
"=",
"0.24",
")",
".",
"Deaths",
"were",
"due",
"to",
"metastatic",
"breast",
"cancer",
"in",
"96",
"%",
"of",
"patients",
".",
"Our",
"data",
"do",
"not",
"support",
"a",
"clinical",
"benefit",
"for",
"simultaneous",
"administration",
"of",
"AD",
"compared",
"with",
"AC",
".",
"However",
",",
"the",
"data",
"do",
"not",
"exclude",
"a",
"smaller",
"benefit",
"than",
"the",
"study",
"was",
"powered",
"to",
"detect",
"and",
"are",
"consistent",
"with",
"an",
"increase",
"in",
"both",
"disease",
"-",
"free",
"and",
"overall",
"survival",
"of",
"about",
"5",
"%",
"for",
"AD",
"compared",
"with",
"AC",
".",
"Outcome",
"is",
"consistent",
"with",
"the",
"pathologic",
"complete",
"response",
"following",
"surgery",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
21,
22,
22,
0,
0,
0,
29,
30,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
29,
30,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
59 | [
"Phase",
"III",
"placebo",
"-",
"controlled",
",",
"double",
"-",
"blind",
",",
"randomized",
"trial",
"of",
"pegfilgrastim",
"to",
"reduce",
"the",
"risk",
"of",
"febrile",
"neutropenia",
"in",
"breast",
"cancer",
"patients",
"receiving",
"docetaxel",
"/",
"cyclophosphamide",
"chemotherapy",
".",
"Pegfilgrastim",
"is",
"a",
"pegylated",
"form",
"of",
"filgrastim",
",",
"a",
"recombinant",
"protein",
"of",
"granulocyte",
"colony",
"-",
"stimulating",
"factor",
",",
"that",
"is",
"used",
"to",
"reduce",
"the",
"risk",
"of",
"febrile",
"neutropenia",
"(",
"FN",
")",
".",
"Here",
",",
"we",
"report",
"the",
"results",
"of",
"a",
"phase",
"III",
"trial",
"of",
"pegfilgrastim",
"in",
"breast",
"cancer",
"patients",
"receiving",
"docetaxel",
"and",
"cyclophosphamide",
"(",
"TC",
")",
"chemotherapy",
".",
"We",
"conducted",
"a",
"double",
"-",
"blind",
",",
"placebo",
"-",
"controlled",
",",
"randomized",
"trial",
"to",
"determine",
"the",
"efficacy",
"of",
"pegfilgrastim",
"in",
"reducing",
"the",
"risk",
"of",
"FN",
"in",
"early",
"-",
"stage",
"breast",
"cancer",
"patients",
".",
"A",
"total",
"of",
"351",
"women",
"(",
"177",
"in",
"the",
"pegfilgrastim",
"group",
"and",
"174",
"in",
"the",
"placebo",
"group",
")",
"between",
"20",
"and",
"69",
"years",
"of",
"age",
"with",
"stage",
"I",
"-",
"III",
"invasive",
"breast",
"carcinoma",
"who",
"were",
"to",
"receive",
"TC",
"chemotherapy",
"(",
"docetaxel",
"75",
"mg",
"/",
"m",
"(",
"2",
")",
"and",
"cyclophosphamide",
"600",
"mg",
"/",
"m",
"(",
"2",
")",
"every",
"3",
"weeks",
")",
"as",
"either",
"neoadjuvant",
"or",
"adjuvant",
"therapy",
"were",
"enrolled",
";",
"346",
"of",
"these",
"patients",
"were",
"treated",
"with",
"either",
"pegfilgrastim",
"(",
"n",
"=",
"173",
")",
"or",
"placebo",
"(",
"n",
"=",
"173",
")",
".",
"The",
"incidence",
"of",
"FN",
"was",
"significantly",
"lower",
"in",
"the",
"pegfilgrastim",
"group",
"than",
"in",
"the",
"placebo",
"group",
"(",
"1.2",
"vs.",
"68.8",
"%",
",",
"respectively",
";",
"P",
"<",
"0.001",
")",
".",
"In",
"addition",
",",
"patients",
"in",
"the",
"pegfilgrastim",
"group",
"required",
"less",
"hospitalization",
"and",
"antibiotics",
"for",
"FN",
".",
"Most",
"adverse",
"events",
"were",
"consistent",
"with",
"those",
"expected",
"for",
"breast",
"cancer",
"subjects",
"receiving",
"TC",
"chemotherapy",
".",
"Pegfilgrastim",
"is",
"safe",
"and",
"significantly",
"reduces",
"the",
"incidence",
"of",
"FN",
"in",
"breast",
"cancer",
"patients",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
13,
14,
0,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
0,
19,
0,
0,
7,
8,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
60 | [
"Phase",
"II",
"study",
"of",
"gemcitabine",
"in",
"combination",
"with",
"vinorelbine",
"versus",
"gemcitabine",
"followed",
"by",
"vinorelbine",
"for",
"metastatic",
"breast",
"cancer",
".",
"No",
"clear",
"data",
"are",
"available",
"concerning",
"the",
"superiority",
"of",
"combination",
"chemotherapy",
"to",
"sequential",
"therapy",
"using",
"agents",
"beyond",
"1",
"st",
"or",
"2",
"nd",
"line",
"chemotherapy",
"for",
"treating",
"patients",
"with",
"metastatic",
"breast",
"cancer",
".",
"Patients",
"were",
"randomized",
"to",
"receive",
"a",
"combination",
"of",
"gemcitabine",
"and",
"vinorelbine",
"or",
"gemcitabine",
"until",
"disease",
"progression",
"followed",
"by",
"vinorelbine",
"monotherapy",
".",
"Quality",
"of",
"life",
"was",
"assessed",
"using",
"EORTC",
"QLQ",
"-",
"C",
"30",
"questionnaires",
".",
"Forty",
"-",
"two",
"patients",
"were",
"randomized",
"to",
"the",
"combination",
"arm",
"and",
"40",
"were",
"randomized",
"to",
"the",
"sequential",
"arm",
".",
"Baseline",
"characteristics",
"were",
"well",
"balanced",
"between",
"the",
"arms",
".",
"The",
"median",
"number",
"of",
"chemotherapy",
"cycles",
"was",
"4",
"(",
"range",
",",
"1",
"-",
"23",
")",
"for",
"the",
"combination",
"arm",
"and",
"6",
"(",
"range",
",",
"1",
"-",
"25",
")",
"for",
"the",
"sequential",
"arm",
".",
"Patients",
"receiving",
"combination",
"therapy",
"had",
"a",
"higher",
"composite",
"response",
"rate",
"(",
"26.8",
"%",
"vs.",
"12.5",
"%",
";",
"P",
"=",
"0.106",
")",
"but",
"a",
"shorter",
"median",
"time",
"to",
"treatment",
"failure",
"(",
"3.6",
"vs.",
"4.4",
"months",
",",
"P",
"=",
"0.252",
")",
"as",
"compared",
"to",
"patients",
"receiving",
"sequential",
"monotherapy",
".",
"Median",
"overall",
"survival",
"for",
"the",
"combination",
"and",
"sequential",
"arms",
"was",
"10.6",
"months",
"and",
"8.9",
"months",
",",
"respectively",
"(",
"P",
"=",
"0.436",
")",
".",
"Toxicities",
"were",
"manageable",
"and",
"similar",
"in",
"both",
"arms",
".",
"Quality",
"of",
"life",
"measurements",
"in",
"global",
"health",
",",
"role",
",",
"and",
"social",
"function",
"were",
"superior",
"in",
"the",
"combination",
"arm",
"(",
"P",
"<",
"0.05",
")",
".",
"Combined",
"gemcitabine",
"and",
"vinorelbine",
"therapy",
"appears",
"comparable",
"to",
"sequential",
"monotherapy",
"for",
"heavily",
"pretreated",
"patients",
"with",
"metastatic",
"breast",
"cancer",
"as",
"demonstrated",
"by",
"improved",
"quality",
"of",
"life",
"outcomes",
"with",
"similar",
"therapeutic",
"efficacies",
"and",
"incidences",
"of",
"adverse",
"events",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
18,
18,
0,
19,
20,
20,
20,
0,
9,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
4,
4,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
37,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
39,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
37,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
37,
38,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
61 | [
"Randomized",
"controlled",
"trial",
"of",
"mindfulness",
"-",
"based",
"stress",
"reduction",
"(",
"MBSR",
")",
"for",
"survivors",
"of",
"breast",
"cancer",
".",
"Considerable",
"morbidity",
"persists",
"among",
"survivors",
"of",
"breast",
"cancer",
"(",
"BC",
")",
"including",
"high",
"levels",
"of",
"psychological",
"stress",
",",
"anxiety",
",",
"depression",
",",
"fear",
"of",
"recurrence",
",",
"and",
"physical",
"symptoms",
"including",
"pain",
",",
"fatigue",
",",
"and",
"sleep",
"disturbances",
",",
"and",
"impaired",
"quality",
"of",
"life",
".",
"Effective",
"interventions",
"are",
"needed",
"during",
"this",
"difficult",
"transitional",
"period",
".",
"We",
"conducted",
"a",
"randomized",
"controlled",
"trial",
"of",
"84",
"female",
"BC",
"survivors",
"(",
"Stages",
"0",
"-III",
")",
"recruited",
"from",
"the",
"H",
".",
"Lee",
"Moffitt",
"Cancer",
"and",
"Research",
"Institute",
".",
"All",
"subjects",
"were",
"within",
"18",
"months",
"of",
"treatment",
"completion",
"with",
"surgery",
"and",
"adjuvant",
"radiation",
"and/or",
"chemotherapy",
".",
"Subjects",
"were",
"randomly",
"assigned",
"to",
"a",
"6",
"-week",
"Mindfulness",
"-",
"Based",
"Stress",
"Reduction",
"(",
"MBSR",
")",
"program",
"designed",
"to",
"self",
"-",
"regulate",
"arousal",
"to",
"stressful",
"circumstances",
"or",
"symptoms",
"(",
"n=",
"41",
")",
"or",
"to",
"usual",
"care",
"(",
"n=",
"43",
")",
".",
"Outcome",
"measures",
"compared",
"at",
"6",
"weeks",
"by",
"random",
"assignment",
"included",
"validated",
"measures",
"of",
"psychological",
"status",
"(",
"depression",
",",
"anxiety",
",",
"perceived",
"stress",
",",
"fear",
"of",
"recurrence",
",",
"optimism",
",",
"social",
"support",
")",
"and",
"psychological",
"and",
"physical",
"subscales",
"of",
"quality",
"of",
"life",
"(",
"SF-",
"36",
")",
".",
"Compared",
"with",
"usual",
"care",
",",
"subjects",
"assigned",
"to",
"MBSR",
"(",
"BC",
")",
"had",
"significantly",
"lower",
"(",
"two",
"-",
"sided",
"p",
"<",
"0.05",
")",
"adjusted",
"mean",
"levels",
"of",
"depression",
"(",
"6.3",
"vs",
"9.6",
")",
",",
"anxiety",
"(",
"28.3",
"vs",
"33.0",
")",
",",
"and",
"fear",
"of",
"recurrence",
"(",
"9.3",
"vs",
"11.6",
")",
"at",
"6",
"weeks",
",",
"along",
"with",
"higher",
"energy",
"(",
"53.5",
"vs",
"49.2",
")",
",",
"physical",
"functioning",
"(",
"50.1",
"vs",
"47.0",
")",
",",
"and",
"physical",
"role",
"functioning",
"(",
"49.1",
"vs",
"42.8",
")",
".",
"In",
"stratified",
"analyses",
",",
"subjects",
"more",
"compliant",
"with",
"MBSR",
"tended",
"to",
"experience",
"greater",
"improvements",
"in",
"measures",
"of",
"energy",
"and",
"physical",
"functioning",
".",
"Among",
"BC",
"survivors",
"within",
"18",
"months",
"of",
"treatment",
"completion",
",",
"a",
"6",
"-week",
"MBSR",
"(",
"BC",
")",
"program",
"resulted",
"in",
"significant",
"improvements",
"in",
"psychological",
"status",
"and",
"quality",
"of",
"life",
"compared",
"with",
"usual",
"care",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
19,
20,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
33,
0,
35,
0,
0,
21,
0,
33,
0,
35,
0,
0,
0,
21,
22,
22,
0,
33,
0,
35,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
33,
0,
35,
0,
0,
21,
22,
0,
33,
0,
35,
0,
0,
0,
21,
22,
22,
0,
33,
0,
35,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
62 | [
"Multidisciplinary",
"rehabilitation",
"in",
"women",
"following",
"breast",
"cancer",
"treatment",
":",
"a",
"randomized",
"controlled",
"trial",
".",
"To",
"assess",
"the",
"effectiveness",
"of",
"a",
"multidisciplinary",
"ambulatory",
"rehabilitation",
"programme",
"for",
"women",
"following",
"definitive",
"breast",
"cancer",
"treatment",
"in",
"an",
"Australian",
"community",
"cohort",
".",
"Eighty",
"-",
"five",
"women",
"in",
"the",
"community",
"randomized",
"to",
"a",
"treatment",
"group",
"(",
"n",
"=",
"43",
")",
"for",
"individualized",
"high",
"-",
"intensity",
"programme",
",",
"or",
"a",
"control",
"group",
"(",
"n",
"=",
"42",
")",
"comprising",
"usual",
"activity",
".",
"The",
"primary",
"outcome",
"Depression",
"Anxiety",
"Stress",
"Scale",
"(",
"DASS",
")",
"scale",
"measured",
"restriction",
"in",
"participation",
".",
"Secondary",
"measures",
"included",
"Perceived",
"Impact",
"Problem",
"Profile",
"(",
"PIPP",
")",
"and",
"Cancer",
"Rehabilitation",
"Evaluation",
"System",
"Short",
"-",
"Form",
"(",
"CARES",
"-",
"SF",
")",
";",
"and",
"Functional",
"Independence",
"Measure",
"(",
"FIM",
")",
"motor",
"subscale",
"for",
"activity",
"limitation",
".",
"Assessments",
"were",
"at",
"baseline",
"and",
"4",
"months",
".",
"Intention",
"-",
"to",
"-",
"treat",
"analysis",
"of",
"data",
"showed",
"a",
"significant",
"difference",
"between",
"both",
"groups",
"in",
"DASS",
"Depression",
"scores",
"(",
"p",
"=",
"0.006",
")",
"(",
"moderate",
"effect",
"size",
",",
"r",
">",
"0.3",
")",
",",
"PIPP",
"Mobility",
"(",
"p",
"=",
"0.05",
")",
"and",
"Participation",
"(",
"p",
"=",
"0.04",
")",
"scales",
",",
"and",
"CARES",
"-",
"SF",
"Global",
"score",
"(",
"p",
"=",
"0.02",
")",
"(",
"small",
"effect",
"size",
",",
"r",
"<",
"0.3",
")",
".",
"The",
"treatment",
"group",
",",
"compared",
"with",
"control",
"group",
",",
"showed",
"significant",
"improvement",
"in",
"the",
"DASS",
"Depression",
"scores",
":",
"22",
"/",
"42",
"(",
"52.4",
"%",
")",
"vs",
"12",
"/",
"37",
"(",
"32.4",
"%",
")",
"(",
"p",
"=",
"0.02",
")",
".",
"No",
"difference",
"between",
"groups",
"was",
"noted",
"in",
"the",
"FIM",
"scale",
".",
"Rehabilitation",
"can",
"benefit",
"participation",
"in",
"breast",
"cancer",
"survivors",
".",
"Evidence",
"for",
"specific",
"rehabilitation",
"interventions",
"is",
"needed",
".",
"Integrated",
"cancer",
"programmes",
"allow",
"opportunities",
"to",
"evaluate",
"patients",
"in",
"various",
"settings",
",",
"but",
"require",
"outcome",
"research",
"to",
"develop",
"service",
"models",
"for",
"survivorship",
"issues",
"."
] | [
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
19,
20,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
25,
0,
3,
0,
29,
30,
0,
0,
27,
0,
5,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
63 | [
"Protocol",
"for",
"the",
"\"",
"Chemobrain",
"in",
"Motion",
"-",
"study",
"\"",
"(",
"CIM",
"-",
"study",
")",
":",
"a",
"randomized",
"placebo",
"-",
"controlled",
"trial",
"of",
"the",
"impact",
"of",
"a",
"high",
"-",
"intensity",
"interval",
"endurance",
"training",
"on",
"cancer",
"related",
"cognitive",
"impairments",
"in",
"women",
"with",
"breast",
"cancer",
"receiving",
"first",
"-",
"line",
"chemotherapy",
".",
"Up",
"to",
"80",
"%",
"of",
"breast",
"cancer",
"patients",
"suffer",
"from",
"Cancer",
"Related",
"Cognitive",
"Impairments",
"(",
"CRCI",
")",
".",
"Exercise",
"is",
"suggested",
"as",
"a",
"potential",
"supportive",
"care",
"option",
"to",
"reduce",
"cognitive",
"decline",
"in",
"cancer",
"patients",
".",
"This",
"study",
"will",
"investigate",
"the",
"effects",
"of",
"a",
"high",
"-",
"intensity",
"interval",
"endurance",
"training",
"(",
"HIIT",
")",
"on",
"CRCI",
"in",
"breast",
"cancer",
"patients",
".",
"Potentially",
"underlying",
"immunological",
"and",
"neurobiological",
"mechanisms",
",",
"as",
"well",
"as",
"effects",
"on",
"patients",
"'",
"self",
"-",
"perceived",
"cognitive",
"functioning",
"and",
"common",
"cancer",
"related",
"side",
"-",
"effects",
",",
"will",
"be",
"explored",
".",
"A",
"single",
"-",
"blinded",
"randomized",
"controlled",
"trial",
"will",
"be",
"carried",
"out",
".",
"The",
"impact",
"of",
"HIIT",
"on",
"CRCI",
"will",
"be",
"compared",
"to",
"that",
"of",
"a",
"placebo",
"-",
"intervention",
"(",
"supervised",
"myofascial",
"release",
"training",
")",
".",
"Both",
"interventions",
"will",
"be",
"conducted",
"simultaneously",
"with",
"the",
"patients",
"'",
"first",
"-",
"line",
"chemotherapy",
"treatment",
"typically",
"lasting",
"12",
"-",
"18",
"weeks",
".",
"Fifty",
"-",
"nine",
"women",
"with",
"breast",
"cancer",
"will",
"be",
"included",
"in",
"each",
"of",
"the",
"two",
"groups",
".",
"The",
"study",
"is",
"powered",
"to",
"detect",
"(",
"α",
"=",
".",
"05",
",",
"β",
"=",
".",
"2",
")",
"a",
"medium",
"effect",
"size",
"difference",
"between",
"the",
"two",
"groups",
"(",
"d",
"=",
".",
"5",
")",
"in",
"terms",
"of",
"patients",
"'",
"change",
"in",
"cognitive",
"testing",
"performances",
",",
"from",
"baseline",
"until",
"the",
"end",
"of",
"the",
"exercise",
"-",
"intervention",
".",
"The",
"cognitive",
"test",
"battery",
",",
"recommended",
"by",
"the",
"International",
"Cancer",
"and",
"Cognition",
"Task",
"Force",
"to",
"assess",
"CRCI",
",",
"will",
"be",
"used",
"as",
"primary",
"measure",
".",
"This",
"includes",
"the",
"Hopkins",
"Verbal",
"Learning",
"Test",
"(",
"learning",
"/",
"verbal",
"memory",
")",
",",
"the",
"Controlled",
"Oral",
"Word",
"Association",
"Test",
"(",
"verbal",
"fluency",
")",
"and",
"the",
"Trail",
"-",
"Making",
"-",
"Test",
"A",
"/",
"B",
"(",
"attention",
"/",
"set",
"-",
"switching",
")",
".",
"The",
"following",
"endpoints",
"will",
"be",
"assessed",
"as",
"secondary",
"measures",
":",
"Go-",
"/",
"No",
"-",
"Go",
"test",
"performance",
"(",
"response",
"inhibition",
")",
",",
"self",
"-",
"perceived",
"cognitive",
"functioning",
",",
"serum",
"levels",
"of",
"pro-",
"and",
"antiinflammatory",
"markers",
"(",
"tumor",
"necrosis",
"factor",
"alpha",
",",
"Interleukin-",
"6",
",",
"Interleukin-",
"1",
"alpha",
",",
"Interleukin-",
"1",
"beta",
",",
"C",
"-",
"reactive",
"protein",
",",
"Interleukin-",
"1",
"receptor",
"antagonist",
"and",
"Interleukin-",
"10",
")",
",",
"serum",
"levels",
"of",
"neurotrophic",
"and",
"growth",
"factors",
"(",
"brain",
"-",
"derived",
"neurotrophic",
"factor",
",",
"insulin",
"-",
"like",
"growth",
"factor",
"1",
"and",
"vascular",
"endothelial",
"growth",
"factor",
")",
",",
"as",
"well",
"as",
"common",
"cancer",
"-",
"related",
"side",
"effects",
"(",
"decrease",
"in",
"physical",
"capacity",
",",
"fatigue",
",",
"anxiety",
"and",
"depression",
",",
"sleep",
"disturbances",
",",
"quality",
"of",
"life",
"and",
"chemotherapy",
"compliance",
")",
".",
"This",
"study",
"will",
"provide",
"data",
"on",
"the",
"question",
"whether",
"HIIT",
"is",
"an",
"effective",
"supportive",
"therapy",
"that",
"alleviates",
"CRCI",
"in",
"breast",
"cancer",
"patients",
".",
"Moreover",
",",
"the",
"present",
"study",
"will",
"help",
"shed",
"light",
"on",
"the",
"underlying",
"mechanisms",
"of",
"potential",
"CRCI",
"improving",
"effects",
"of",
"exercise",
"in",
"breast",
"cancer",
"patients",
".",
"DRKS.de",
",",
"German",
"Clinical",
"Trials",
"Register",
"(",
"DRKS",
")",
",",
"ID",
":",
"DRKS",
"00011390",
",",
"Registered",
"on",
"17",
"January",
"2018",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
64 | [
"A",
"randomized",
"control",
"study",
"of",
"treating",
"secondary",
"stage",
"II",
"breast",
"cancer",
"-",
"related",
"lymphoedema",
"with",
"free",
"lymph",
"node",
"transfer",
".",
"Microsurgical",
"techniques",
"are",
"increasingly",
"used",
"for",
"treating",
"severe",
"lymphoedema",
"cases",
".",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"evaluate",
"the",
"effectiveness",
"of",
"free",
"vascularized",
"lymph",
"node",
"transfer",
"(",
"LNT",
")",
"in",
"stage",
"II",
"breast",
"cancer",
"-",
"related",
"lymphoedema",
"patients",
"in",
"comparison",
"with",
"non",
"-",
"surgical",
"management",
".",
"During",
"the",
"last",
"3",
"years",
",",
"83",
"female",
"patients",
"were",
"examined",
"at",
"our",
"lymphoedema",
"clinic",
".",
"Finally",
",",
"36",
"cases",
"were",
"included",
"in",
"this",
"study",
"and",
"randomly",
"divided",
"in",
"two",
"groups",
":",
"group",
"A",
"patients",
"(",
"n",
"=",
"18",
",",
"mean",
"age",
"47",
"years",
")",
"underwent",
"microsurgical",
"LNT",
";",
"followed",
"by",
"6",
"months",
"of",
"physiotherapy",
"and",
"compression",
",",
"while",
"group",
"B",
"patients",
"(",
"n",
"=",
"18",
",",
"mean",
"age",
"49",
"years",
")",
"were",
"managed",
"by",
"physiotherapy",
"and",
"compression",
"alone",
"for",
"6",
"months",
".",
"Patients",
"of",
"both",
"groups",
"removed",
"their",
"elastic",
"garments",
"after",
"6",
"months",
"and",
"were",
"re",
"-",
"examined",
"1",
"year",
"later",
".",
"All",
"the",
"36",
"patients",
"had",
"detailed",
"evaluation",
"of",
"the",
"affected",
"extremity",
"including",
"limb",
"volume",
"measurement",
",",
"infection",
"episodes",
"and",
"scale",
"scoring",
"of",
"pain",
",",
"feeling",
"of",
"heaviness",
"and",
"functional",
"status",
"both",
"at",
"baseline",
"and",
"18",
"month",
".",
"Limb",
"volume",
"reduction",
"was",
"observed",
"in",
"both",
"groups",
";",
"mean",
"reduction",
"was",
"greater",
"in",
"group",
"A",
"(",
"57",
"%",
")",
"than",
"in",
"group",
"B",
"(",
"18",
"%",
")",
".",
"Infection",
"episodes",
"in",
"group",
"A",
"were",
"significantly",
"reduced",
"compared",
"to",
"those",
"in",
"group",
"B",
"patients",
".",
"All",
"group",
"A",
"patients",
"reported",
"painless",
"and",
"feeling",
"of",
"heaviness",
"-",
"free",
"extremities",
"with",
"overall",
"functional",
"improvement",
",",
"while",
"the",
"corresponding",
"changes",
"in",
"group",
"B",
"patients",
"were",
"no",
"more",
"than",
"marginal",
".",
"Moreover",
",",
"the",
"LNT",
"procedure",
"was",
"estimated",
"as",
"cost",
"effective",
"compared",
"to",
"conservative",
"treatment",
"alone",
".",
"LNT",
"represents",
"an",
"effective",
"therapeutic",
"approach",
"for",
"stage",
"II",
"lymphoedema",
"patients",
";",
"it",
"significantly",
"reduces",
"limb",
"volume",
",",
"decreases",
"recurrent",
"infections",
"and",
"improves",
"the",
"overall",
"function",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
7,
8,
0,
0,
17,
18,
18,
18,
18,
18,
18,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
7,
8,
0,
0,
0,
0,
19,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
65 | [
"Progressive",
"resistance",
"versus",
"relaxation",
"training",
"for",
"breast",
"cancer",
"patients",
"during",
"adjuvant",
"chemotherapy",
":",
"design",
"and",
"rationale",
"of",
"a",
"randomized",
"controlled",
"trial",
"(",
"BEATE",
"study",
")",
".",
"Cancer",
"-",
"related",
"fatigue",
"is",
"a",
"common",
"severe",
"symptom",
"in",
"breast",
"cancer",
"patients",
",",
"especially",
"during",
"chemotherapy",
".",
"Exercise",
"appears",
"to",
"be",
"promising",
"in",
"prevention",
"or",
"treatment",
"of",
"fatigue",
".",
"Resistance",
"training",
"as",
"an",
"accompanying",
"treatment",
"to",
"chemotherapy",
"has",
"been",
"minimally",
"investigated",
",",
"yet",
"might",
"counteract",
"muscle",
"degradation",
"and",
"inflammation",
"caused",
"by",
"many",
"chemotherapeutics",
",",
"and",
"thus",
"forestall",
"or",
"reduce",
"fatigue",
".",
"Previous",
"exercise",
"trials",
"mostly",
"compared",
"the",
"intervention",
"with",
"'",
"usual",
"care",
"'",
".",
"Therefore",
",",
"it",
"is",
"unclear",
"to",
"what",
"extent",
"the",
"observed",
"effects",
"on",
"fatigue",
"are",
"based",
"on",
"physical",
"adaptations",
"by",
"exercise",
"itself",
",",
"or",
"rather",
"on",
"psycho",
"-",
"social",
"factors",
"linked",
"to",
"the",
"group",
"support",
"or",
"attention",
"by",
"the",
"trainer",
".",
"The",
"BEATE",
"study",
"is",
"a",
"randomized",
",",
"controlled",
"intervention",
"trial",
"comparing",
"a",
"12",
"-week",
"supervised",
"progressive",
"resistance",
"training",
"program",
"with",
"a",
"supervised",
"group",
"-",
"based",
"progressive",
"muscle",
"relaxation",
"training",
"in",
"100",
"patients",
"with",
"breast",
"cancer",
"under",
"adjuvant",
"chemotherapy",
".",
"The",
"primary",
"endpoint",
"is",
"cancer",
"-",
"related",
"fatigue",
";",
"secondary",
"endpoints",
"include",
"quality",
"of",
"life",
",",
"depression",
",",
"and",
"cognitive",
"capacity",
".",
"In",
"addition",
",",
"isokinetic",
"and",
"isometric",
"muscle",
"strength",
",",
"cardiorespiratory",
"fitness",
",",
"and",
"body",
"composition",
"are",
"measured",
",",
"and",
"biomarkers",
",",
"such",
"as",
"inflammatory",
"parameters",
",",
"cortisol",
",",
"and",
"oxidative",
"stress",
"are",
"analyzed",
"in",
"blood",
",",
"saliva",
"and",
"urine",
".",
"Safety",
"of",
"the",
"resistance",
"training",
"during",
"chemotherapy",
"is",
"monitored",
".",
"Strengths",
"of",
"the",
"BEATE",
"study",
"include",
"the",
"investigation",
"of",
"progressive",
"resistance",
"training",
"parallel",
"with",
"chemotherapy",
",",
"the",
"choice",
"of",
"a",
"control",
"group",
"that",
"enables",
"an",
"evaluation",
"of",
"the",
"physiological",
"effects",
"of",
"exercise",
"beyond",
"potential",
"psycho",
"-",
"social",
"effects",
",",
"and",
"the",
"comprehensive",
"and",
"high",
"-",
"quality",
"assessment",
"of",
"physiological",
"factors",
"and",
"biomarkers",
"potentially",
"related",
"to",
"fatigue",
"."
] | [
17,
18,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
23,
24,
24,
24,
0,
0,
0,
0,
23,
24,
24,
0,
23,
0,
0,
23,
24,
0,
0,
0,
0,
23,
24,
24,
24,
24,
0,
23,
24,
0,
0,
23,
24,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
66 | [
"Dose",
"-",
"dependent",
"effect",
"of",
"aerobic",
"exercise",
"on",
"inflammatory",
"biomarkers",
"in",
"a",
"randomized",
"controlled",
"trial",
"of",
"women",
"at",
"high",
"risk",
"of",
"breast",
"cancer",
".",
"Increased",
"levels",
"of",
"inflammation",
"are",
"associated",
"with",
"many",
"diseases",
",",
"including",
"cancer",
".",
"Physical",
"activity",
"can",
"lower",
"breast",
"cancer",
"risk",
"as",
"well",
"as",
"levels",
"of",
"inflammation",
".",
"The",
"Women",
"In",
"Steady",
"Exercise",
"Research",
"(",
"WISER",
")",
"Sister",
"trial",
"was",
"a",
"randomized",
"controlled",
"trial",
"that",
"investigated",
"the",
"effects",
"of",
"a",
"dosed",
",",
"moderate",
"to",
"vigorous",
",",
"aerobic",
"exercise",
"intervention",
"on",
"levels",
"of",
"inflammation",
"in",
"premenopausal",
"women",
"who",
"were",
"at",
"high",
"risk",
"of",
"developing",
"breast",
"cancer",
".",
"Participants",
"were",
"randomized",
"to",
"control",
"(",
"<",
"75",
"minutes",
"per",
"week",
";",
"41",
"patients",
")",
",",
"low",
"-",
"dose",
"exercise",
"(",
"150",
"minutes",
"per",
"week",
";",
"38",
"patients",
")",
",",
"or",
"high",
"-",
"dose",
"exercise",
"(",
"300",
"minutes",
"per",
"week",
";",
"37",
"patients",
")",
"groups",
".",
"The",
"5",
"-menstrual",
"cycles",
"-",
"long",
",",
"home",
"-",
"based",
"treadmill",
"exercise",
"intervention",
"gradually",
"increased",
"in",
"minutes",
"per",
"week",
"and",
"intensity",
"up",
"to",
"a",
"maximum",
"of",
"80",
"%",
"of",
"the",
"age",
"-",
"predicted",
"maximum",
"heart",
"rate",
".",
"Blood",
"was",
"collected",
"at",
"baseline",
"and",
"at",
"follow",
"-",
"up",
"and",
"assayed",
"for",
"chemokine",
"(",
"C",
"-",
"C",
"motif",
")",
"ligand",
"2",
"(",
"CCL",
"2",
")",
",",
"interleukin",
"10",
"(",
"IL-",
"10",
")",
",",
"interleukin",
"12",
"(",
"IL-",
"12",
")",
",",
"and",
"tumor",
"necrosis",
"factor",
"α",
"(",
"TNF",
"-",
"α",
")",
".",
"A",
"linear",
"dose",
"-",
"response",
"relationship",
"was",
"observed",
"for",
"the",
"proinflammatory",
"biomarkers",
"CCL",
"2",
"(",
"%",
"Δ",
"of",
"-",
"5.44",
"%",
"in",
"the",
"control",
"group",
",",
"-",
"0.03",
"%",
"in",
"the",
"low",
"-",
"dose",
"exercise",
"group",
",",
"and",
"1.54",
"%",
"in",
"the",
"high",
"-",
"dose",
"exercise",
"group",
")",
",",
"IL-",
"12",
"(",
"%",
"Δ",
"of",
"-",
"21.5",
"%",
"in",
"the",
"control",
"group",
",",
"38.2",
"%",
"in",
"the",
"low",
"-",
"dose",
"exercise",
"group",
",",
"and",
"25.8",
"%",
"in",
"the",
"high",
"-",
"dose",
"exercise",
"group",
",",
")",
"and",
"TNF",
"-",
"α",
"(",
"%",
"Δ",
"of",
"-",
"4.69",
"%",
"in",
"the",
"control",
"group",
",",
"9.51",
"%",
"in",
"the",
"low",
"-",
"dose",
"exercise",
"group",
",",
"and",
"15.7",
"%",
"in",
"the",
"high",
"-",
"dose",
"exercise",
"group",
")",
"but",
"not",
"for",
"the",
"anti",
"-",
"inflammatory",
"biomarker",
"IL-",
"10",
"(",
"%",
"Δ",
"of",
"5.05",
"%",
"in",
"the",
"control",
"group",
",",
"6.05",
"%",
"in",
"the",
"low",
"-",
"dose",
"exercise",
"group",
",",
"and",
"10.6",
"%",
"in",
"the",
"high",
"-",
"dose",
"exercise",
"group",
")",
".",
"For",
"IL-",
"12",
"and",
"TNF",
"-",
"α",
",",
"the",
"percentage",
"change",
"was",
"significantly",
"higher",
"in",
"the",
"low",
"-",
"dose",
"(",
"IL-",
"12",
":",
"P",
"<",
".",
"001",
";",
"and",
"TNF",
"-",
"α",
":",
"P",
"=",
".",
"01",
")",
"and",
"high",
"-",
"dose",
"(",
"IL-",
"12",
":",
"P",
"<",
".",
"001",
";",
"and",
"TNF",
"-",
"α",
":",
"P",
"<",
".",
"001",
")",
"exercise",
"groups",
"compared",
"with",
"the",
"control",
"group",
".",
"Moderate",
"to",
"vigorous",
"aerobic",
"exercise",
"appeared",
"to",
"increase",
"levels",
"of",
"proinflammatory",
"biomarkers",
"in",
"a",
"dose",
"-",
"dependent",
"manner",
"in",
"a",
"population",
"of",
"healthy",
"women",
"at",
"high",
"risk",
"of",
"developing",
"breast",
"cancer",
".",
"The",
"results",
"of",
"the",
"current",
"study",
"suggest",
"that",
"for",
"healthy",
"premenopausal",
"women",
",",
"the",
"mechanism",
"of",
"reduced",
"breast",
"cancer",
"risk",
"observed",
"in",
"physically",
"active",
"individuals",
"may",
"not",
"be",
"a",
"result",
"of",
"reduced",
"levels",
"of",
"inflammation",
"."
] | [
0,
0,
0,
0,
0,
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
67 | [
"Ultrasound",
"-",
"guided",
"serratus",
"plane",
"block",
"enhances",
"pain",
"relief",
"and",
"quality",
"of",
"recovery",
"after",
"breast",
"cancer",
"surgery",
":",
"A",
"randomised",
"controlled",
"trial",
".",
"Multimodal",
"analgesia",
"can",
"improve",
"postoperative",
"pain",
"and",
"possibly",
"accelerate",
"functional",
"recovery",
"after",
"surgery",
".",
"Serratus",
"plane",
"block",
"(",
"SPB",
")",
"is",
"a",
"novel",
",",
"ultrasound",
"-",
"guided",
"regional",
"anaesthetic",
"technique",
"for",
"complete",
"analgesia",
"of",
"the",
"anterolateral",
"chest",
"wall",
".",
"But",
",",
"the",
"effect",
"of",
"SPB",
"on",
"the",
"quality",
"of",
"recovery",
"after",
"breast",
"cancer",
"surgery",
"has",
"not",
"been",
"established",
".",
"To",
"test",
"the",
"hypothesis",
"that",
"pre",
"-",
"operative",
"SPB",
"would",
"enhance",
"the",
"quality",
"of",
"recovery",
"following",
"breast",
"cancer",
"surgery",
".",
"A",
"randomised",
",",
"double",
"-",
"blind",
",",
"parallel",
"-",
"group",
",",
"placebo",
"-",
"controlled",
"trial",
".",
"Single",
"university",
"teaching",
"hospital",
",",
"from",
"March",
"2016",
"to",
"June",
"2017",
".",
"Seventy",
"-",
"two",
"women",
"scheduled",
"for",
"breast",
"cancer",
"surgery",
".",
"Participants",
"were",
"randomised",
"in",
"a",
"1",
":",
"1",
"ratio",
"to",
"receive",
"SPB",
"with",
"25",
"ml",
"of",
"ropivacaine",
"0.5",
"%",
"or",
"physiological",
"saline",
".",
"The",
"primary",
"endpoint",
"was",
"the",
"40",
"-item",
"Quality",
"of",
"Recovery",
"questionnaire",
"score",
"24",
"hours",
"postoperatively",
"hours",
".",
"Secondary",
"endpoints",
"were",
"postoperative",
"pain",
"intensity",
",",
"cumulative",
"opioid",
"consumption",
",",
"postoperative",
"nausea",
"and",
"vomiting",
",",
"dizziness",
",",
"post",
"anaesthesia",
"care",
"unit",
"discharge",
"time",
"and",
"patient",
"satisfaction",
".",
"The",
"global",
"median",
"[",
"IQR",
"]",
"40",
"-item",
"Quality",
"of",
"Recovery",
"questionnaire",
"score",
"at",
"24",
"postoperative",
"hours",
"was",
"significantly",
"higher",
"in",
"the",
"SPB",
"group",
"(",
"158",
"[",
"153.8",
"to",
"159.3",
"]",
")",
"than",
"the",
"control",
"group",
"(",
"141",
"[",
"139",
"to",
"145.3",
"]",
")",
"with",
"a",
"median",
"difference",
"of",
"15",
"(",
"95",
"%",
"confidence",
"interval",
":",
"13",
"to",
"17",
",",
"P",
"<",
"0.001",
")",
".",
"Compared",
"with",
"the",
"control",
"group",
",",
"postoperative",
"pain",
"scores",
"at",
"rest",
"were",
"significantly",
"lower",
"up",
"to",
"24",
"h",
"in",
"the",
"SPB",
"group",
".",
"Pre",
"-",
"operative",
"SPB",
"reduced",
"postoperative",
"cumulative",
"opioid",
"consumption",
",",
"the",
"incidence",
"of",
"postoperative",
"nausea",
"and",
"vomiting",
"and",
"the",
"post",
"anaesthesia",
"care",
"unit",
"discharge",
"time",
".",
"In",
"addition",
",",
"patient",
"satisfaction",
"scores",
"were",
"higher",
"in",
"the",
"SPB",
"group",
".",
"Pre",
"-",
"operative",
"administration",
"of",
"SPB",
"with",
"ropivacaine",
"improved",
"the",
"quality",
"of",
"recovery",
",",
"postoperative",
"analgesia",
"and",
"patient",
"satisfaction",
"following",
"breast",
"cancer",
"surgery",
".",
"ClinicalTrials.gov",
"(",
"identifier",
":",
"NCT",
"02691195",
")",
"."
] | [
17,
18,
18,
18,
18,
18,
0,
13,
14,
14,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
23,
24,
24,
0,
23,
24,
24,
0,
23,
24,
24,
24,
0,
23,
0,
23,
24,
24,
24,
24,
24,
0,
23,
24,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
37,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
39,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
68 | [
"A",
"Randomized",
",",
"Single",
"-",
"Blind",
"Study",
"Evaluating",
"the",
"Effect",
"of",
"a",
"Bone",
"Pain",
"Education",
"Video",
"on",
"Reported",
"Bone",
"Pain",
"in",
"Patients",
"with",
"Breast",
"Cancer",
"Receiving",
"Chemotherapy",
"and",
"Pegfilgrastim",
".",
"Mild",
"-",
"to",
"-",
"moderate",
"bone",
"pain",
"is",
"the",
"most",
"commonly",
"reported",
"adverse",
"event",
"associated",
"with",
"pegfilgrastim",
".",
"To",
"investigate",
"the",
"effect",
"of",
"bone",
"pain",
"education",
"on",
"pegfilgrastim",
"-",
"related",
"bone",
"pain",
"in",
"patients",
"with",
"breast",
"cancer",
"receiving",
"chemotherapy",
"and",
"pegfilgrastim",
".",
"Randomized",
",",
"single",
"-",
"blind",
"study",
".",
"Forty",
"-",
"eight",
"community",
"oncology",
"clinics",
"throughout",
"the",
"United",
"States",
".",
"Three",
"hundred",
"women",
"≥",
"18",
"years",
"of",
"age",
"with",
"newly",
"diagnosed",
"stage",
"I",
"-III",
"breast",
"cancer",
",",
"who",
"were",
"planning",
"≥",
"4",
"cycles",
"of",
"neoadjuvant",
"or",
"adjuvant",
"chemotherapy",
"with",
"pegfilgrastim",
"support",
"starting",
"in",
"cycle",
"1",
".",
"Patients",
"were",
"randomized",
"1",
":1",
"to",
"view",
"a",
"general",
"education",
"DVD",
"on",
"chemotherapy",
"side",
"effects",
"(",
"GE",
"-",
"DVD",
")",
"or",
"a",
"DVD",
"on",
"bone",
"pain",
"following",
"chemotherapy",
"and",
"pegfilgrastim",
"(",
"BP",
"-",
"DVD",
")",
".",
"Patients",
"recorded",
"severity",
"of",
"bone",
"pain",
"on",
"a",
"scale",
"of",
"0",
"-",
"10",
",",
"location",
"of",
"pain",
",",
"and",
"use",
"of",
"bone",
"pain",
"medications",
"(",
"i.e.",
",",
"analgesics",
",",
"antihistamines",
",",
"and",
"nonsteroidal",
"anti",
"-",
"inflammatory",
"drugs",
")",
"for",
"5",
"days",
",",
"beginning",
"on",
"the",
"day",
"of",
"pegfilgrastim",
"administration",
",",
"in",
"each",
"of",
"the",
"first",
"four",
"chemotherapy",
"cycles",
".",
"Patient",
"-",
"reported",
"maximum",
"bone",
"pain",
"was",
"similar",
"in",
"the",
"two",
"groups",
"(",
"GE",
"-",
"DVD",
"vs",
"BP",
"-",
"DVD",
":",
"cycle",
"1",
",",
"3.2",
"vs.",
"3.5",
",",
"p",
"=",
".",
"3479",
";",
"across",
"all",
"cycles",
",",
"4.1",
"vs.",
"4.6",
",",
"p",
"=",
".",
"2196",
")",
".",
"Other",
"measures",
"of",
"bone",
"pain",
"were",
"also",
"similar",
"between",
"the",
"groups",
".",
"Bone",
"pain",
"was",
"highest",
"in",
"cycle",
"1",
"but",
"decreased",
"and",
"then",
"remained",
"stable",
"in",
"subsequent",
"cycles",
".",
"Bone",
"pain",
"medication",
"use",
"was",
"similar",
"in",
"both",
"groups",
"and",
"was",
"highest",
"in",
"cycle",
"1",
".",
"The",
"bone",
"pain",
"-",
"specific",
"education",
"evaluated",
"here",
"did",
"not",
"improve",
"perceptions",
"of",
"bone",
"pain",
"reported",
"in",
"this",
"patient",
"population",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
18,
0,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
0,
1,
2,
0,
7,
8,
8,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
0,
33,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
69 | [
"Randomized",
"trial",
"of",
"proactive",
"rapid",
"genetic",
"counseling",
"versus",
"usual",
"care",
"for",
"newly",
"diagnosed",
"breast",
"cancer",
"patients",
".",
"Breast",
"cancer",
"patients",
"who",
"carry",
"BRCA",
"1",
"/",
"BRCA",
"2",
"gene",
"mutations",
"may",
"consider",
"bilateral",
"mastectomy",
".",
"Having",
"bilateral",
"mastectomy",
"at",
"the",
"time",
"of",
"diagnosis",
"not",
"only",
"reduces",
"risk",
"of",
"a",
"contralateral",
"breast",
"cancer",
",",
"but",
"can",
"eliminate",
"the",
"need",
"for",
"radiation",
"therapy",
"and",
"yield",
"improved",
"reconstruction",
"options",
".",
"However",
",",
"most",
"patients",
"do",
"not",
"receive",
"genetic",
"counseling",
"or",
"testing",
"at",
"the",
"time",
"of",
"their",
"diagnosis",
".",
"In",
"this",
"trial",
",",
"we",
"tested",
"proactive",
"rapid",
"genetic",
"counseling",
"and",
"testing",
"(",
"RGCT",
")",
"in",
"newly",
"diagnosed",
"breast",
"cancer",
"patients",
"in",
"order",
"to",
"facilitate",
"pre",
"-",
"surgical",
"genetic",
"counseling",
"and",
"testing",
".",
"We",
"recruited",
"newly",
"diagnosed",
"breast",
"cancer",
"patients",
"at",
"increased",
"risk",
"for",
"carrying",
"a",
"BRCA",
"1",
"/",
"2",
"mutation",
".",
"Of",
"379",
"eligible",
"patients",
"who",
"completed",
"a",
"baseline",
"survey",
",",
"330",
"agreed",
"to",
"randomization",
"in",
"a",
"2",
":1",
"ratio",
"to",
"RGCT",
"(",
"n",
"=",
"220",
")",
"versus",
"UC",
"(",
"n",
"=",
"108",
")",
".",
"Primary",
"outcomes",
"were",
"genetic",
"counseling",
"and",
"testing",
"uptake",
"and",
"breast",
"cancer",
"surgical",
"decisions",
".",
"RGCT",
"led",
"to",
"higher",
"overall",
"(",
"83.8",
"%",
"vs.",
"54.6",
"%",
";",
"p",
"<",
"0.0001",
")",
"and",
"pre",
"-",
"surgical",
"(",
"57.8",
"%",
"vs.",
"38.7",
"%",
";",
"p",
"=",
"0.001",
")",
"genetic",
"counseling",
"uptake",
"compared",
"to",
"UC",
".",
"Despite",
"higher",
"rates",
"of",
"genetic",
"counseling",
",",
"RGCT",
"did",
"not",
"differ",
"from",
"UC",
"in",
"overall",
"(",
"54.1",
"%",
"vs.",
"49.1",
"%",
",",
"p",
">",
"0.10",
")",
"or",
"pre",
"-",
"surgical",
"(",
"30.6",
"%",
"vs.",
"27.4",
"%",
",",
"p",
">",
"0.10",
")",
"receipt",
"of",
"genetic",
"test",
"results",
"nor",
"did",
"they",
"differ",
"in",
"uptake",
"of",
"bilateral",
"mastectomy",
"(",
"26.6",
"%",
"vs.",
"21.8",
"%",
",",
"p",
">",
"0.10",
")",
".",
"Although",
"RGCT",
"yielded",
"increased",
"genetic",
"counseling",
"participation",
",",
"this",
"did",
"not",
"result",
"in",
"increased",
"rates",
"of",
"pre",
"-",
"surgical",
"genetic",
"testing",
"or",
"impact",
"surgical",
"decisions",
".",
"These",
"data",
"suggest",
"that",
"those",
"patients",
"most",
"likely",
"to",
"opt",
"for",
"genetic",
"testing",
"at",
"the",
"time",
"of",
"diagnosis",
"are",
"being",
"effectively",
"identified",
"by",
"their",
"surgeons",
"."
] | [
0,
0,
0,
17,
18,
18,
18,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
0,
23,
24,
24,
24,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
70 | [
"Measuring",
"the",
"impact",
"of",
"guideline",
"-",
"based",
"antiemetic",
"therapy",
"on",
"nausea",
"and",
"vomiting",
"control",
"in",
"breast",
"cancer",
"patients",
"with",
"multiple",
"risk",
"factors",
".",
"The",
"objective",
"of",
"this",
"exploratory",
"analysis",
"was",
"to",
"determine",
"if",
"individual",
"patient",
"risk",
"factors",
"could",
"be",
"used",
"to",
"optimize",
"chemotherapy",
"-",
"induced",
"nausea",
"and",
"vomiting",
"(",
"CINV",
")",
".",
"Through",
"validated",
"risk",
"prediction",
"models",
"which",
"quantify",
"patient",
"risk",
"factors",
",",
"152",
"patients",
"with",
"early",
"-",
"stage",
"breast",
"cancer",
"scheduled",
"to",
"received",
"adjuvant",
"anthracycline",
"-",
"based",
"chemotherapy",
"were",
"categorized",
"as",
"being",
"at",
"low",
"(",
"level",
"0",
")",
"or",
"high",
"-",
"risk",
"(",
"level",
"1",
")",
"for",
"CINV",
".",
"Prior",
"to",
"the",
"first",
"cycle",
"of",
"chemotherapy",
",",
"low",
"-",
"risk",
"patients",
"received",
"ondansetron",
"and",
"dexamethasone",
",",
"while",
"high",
"-",
"risk",
"level",
"1",
"patients",
"also",
"received",
"aprepitant",
".",
"For",
"subsequent",
"cycles",
",",
"patients",
"who",
"experienced",
"CINV",
"had",
"their",
"antiemetics",
"changed",
"in",
"a",
"stepwise",
"manner",
"to",
"level",
"2",
"(",
"extended",
"-",
"duration",
"dexamethasone",
")",
"or",
"level",
"3",
"(",
"extended",
"-",
"duration",
"dexamethasone",
"and",
"low",
"-",
"dose",
"olanzapine",
")",
".",
"The",
"study",
"enrolled",
"152",
"patients",
"who",
"received",
"484",
"cycles",
"of",
"chemotherapy",
".",
"Forty",
"patient",
"cycles",
"were",
"classified",
"as",
"low",
"risk",
"(",
"level",
"0",
")",
"compared",
"to",
"201",
",",
"162",
"and",
"81",
"that",
"were",
"classified",
"as",
"high",
"-",
"risk",
"levels",
"1",
",",
"2",
"and",
"3",
",",
"respectively",
".",
"Complete",
"control",
"of",
"acute",
"and",
"delayed",
"vomiting",
"was",
"comparable",
"and",
"was",
"achieved",
"in",
"over",
"85",
"%",
"of",
"patients",
"across",
"all",
"risk",
"levels",
"(",
"p",
"=",
"0.56",
"and",
"p",
"=",
"0.99",
")",
".",
"In",
"contrast",
",",
"complete",
"control",
"of",
"acute",
"and",
"delayed",
"nausea",
"was",
"reduced",
"in",
"risk",
"levels",
"1",
"to",
"3",
"compared",
"to",
"level",
"0",
"(",
"acute",
"=",
"51.2",
",",
"58.0",
",",
"45.7",
"vs.",
"70.0",
"%",
";",
"p",
"=",
"0.013",
")",
"-",
"(",
"delayed",
"=",
"32.8",
",",
"45.7",
",",
"34.6",
"vs.",
"62.5",
"%",
";",
"p",
"<",
"0.001",
")",
".",
"Despite",
"the",
"addition",
"of",
"aprepitant",
",",
"extended",
"-",
"duration",
"dexamethasone",
"and",
"olanzapine",
",",
"patients",
"at",
"high",
"risk",
"for",
"CINV",
"due",
"to",
"personal",
"risk",
"factors",
"failed",
"to",
"achieve",
"good",
"nausea",
"control",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
18,
18,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
71 | [
"Effect",
"of",
"Topical",
"Anesthetic",
"Cream",
"on",
"Pain",
"During",
"Periareolar",
"Injection",
"of",
"Technetium",
"Tc",
"99",
"m",
"Sulfur",
"Colloid",
"for",
"Sentinel",
"Lymph",
"Node",
"Biopsy",
"in",
"Breast",
"Cancer",
":",
"A",
"Randomized",
"Control",
"Trial",
".",
"Injection",
"of",
"Tc",
"99",
"m",
"to",
"localize",
"nodes",
"for",
"sentinel",
"lymph",
"node",
"biopsy",
"is",
"reported",
"by",
"patients",
"as",
"very",
"painful",
".",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"determine",
"if",
"anesthetic",
"cream",
"reduces",
"pain",
"associated",
"with",
"periareolar",
"injection",
"of",
"Tc",
"99",
"m",
"and",
"to",
"help",
"elucidate",
"conflicting",
"literature",
"regarding",
"the",
"efficacy",
"of",
"anesthetic",
"cream",
"for",
"this",
"procedure",
".",
"A",
"randomized",
",",
"double",
"-",
"blind",
",",
"placebo",
"-",
"controlled",
"methodology",
"was",
"used",
"for",
"adult",
"females",
"with",
"breast",
"cancer",
"undergoing",
"periareolar",
"injection",
"of",
"Tc",
"99",
"m",
"for",
"sentinel",
"lymph",
"node",
"biopsy",
".",
"Pain",
"levels",
"were",
"compared",
"using",
"anesthetic",
"cream",
"(",
"2.5",
"%",
"lidocaine",
"/",
"2.5",
"%",
"prilocaine",
")",
"vs.",
"placebo",
".",
"Patient",
"exclusion",
"criteria",
"included",
"use",
"of",
"opioids",
"or",
"adjuvant",
"pain",
"medication",
"or",
"injecting",
"Tc",
"99",
"m",
"the",
"day",
"before",
"surgery",
".",
"The",
"Numerical",
"Rating",
"Scale",
"was",
"used",
"to",
"assess",
"pain",
"levels",
"immediately",
"after",
"the",
"injections",
".",
"Comparing",
"23",
"experimental",
"and",
"26",
"control",
"patients",
",",
"there",
"was",
"no",
"significant",
"difference",
"between",
"the",
"experimental",
"(",
"median",
"=",
"4",
")",
"and",
"the",
"control",
"group",
"(",
"median",
"=",
"5",
")",
"on",
"level",
"of",
"pain",
"experienced",
"U=",
"0.492",
",",
"P",
">",
".",
"05",
".",
"The",
"experimental",
"group",
"had",
"a",
"slightly",
"lower",
"median",
"pain",
"score",
";",
"however",
",",
"there",
"was",
"no",
"statistically",
"significant",
"difference",
"between",
"those",
"who",
"used",
"the",
"cream",
"compared",
"with",
"those",
"who",
"used",
"a",
"placebo",
",",
"supporting",
"the",
"conclusion",
"that",
"anesthetic",
"cream",
"does",
"not",
"reduce",
"pain",
"during",
"Tc",
"99",
"m",
"injections",
".",
"This",
"study",
"adds",
"to",
"the",
"current",
"literature",
"to",
"provide",
"a",
"stronger",
"position",
"that",
"there",
"is",
"no",
"benefit",
"to",
"using",
"anesthetic",
"cream",
"for",
"this",
"procedure",
"."
] | [
0,
0,
17,
18,
18,
0,
13,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
72 | [
"Mammographic",
"density",
"change",
"with",
"1",
"year",
"of",
"aerobic",
"exercise",
"among",
"postmenopausal",
"women",
":",
"a",
"randomized",
"controlled",
"trial",
".",
"The",
"Alberta",
"Physical",
"Activity",
"and",
"Breast",
"Cancer",
"Prevention",
"(",
"ALPHA",
")",
"Trial",
"examined",
"the",
"influence",
"of",
"aerobic",
"exercise",
"on",
"biological",
"factors",
"that",
"are",
"associated",
"with",
"breast",
"cancer",
"risk",
".",
"Mammographic",
"density",
",",
"a",
"secondary",
"outcome",
",",
"is",
"reported",
"here",
".",
"The",
"ALPHA",
"Trial",
"was",
"a",
"parallel",
"group",
"randomized",
"controlled",
"trial",
"conducted",
"between",
"May",
"2003",
"and",
"July",
"2007",
".",
"Postmenopausal",
",",
"sedentary",
"women",
"ages",
"50",
"to",
"74",
"years",
"(",
"n",
"=",
"320",
")",
"were",
"evenly",
"randomized",
"to",
"aerobic",
"exercise",
"(",
"45",
"minutes",
",",
"5",
"days",
"per",
"week",
")",
"or",
"control",
"(",
"usual",
"life",
"-",
"style",
")",
"for",
"1",
"year",
".",
"Dense",
"fibroglandular",
"tissue",
"and",
"nondense",
"fatty",
"tissue",
"were",
"measured",
"from",
"mammograms",
"at",
"baseline",
"and",
"1",
"year",
"using",
"computer",
"-",
"assisted",
"thresholding",
"software",
"for",
"area",
"measurements",
"and",
"a",
"new",
"technique",
"that",
"relies",
"on",
"the",
"calibration",
"of",
"mammography",
"units",
"with",
"a",
"tissue",
"-",
"equivalent",
"phantom",
"for",
"volumetric",
"measurements",
".",
"Nondense",
"volume",
"decreased",
"in",
"the",
"exercise",
"group",
"relative",
"to",
"the",
"control",
"group",
"(",
"difference",
"between",
"groups",
"=",
"-",
"38.5",
"cm",
"(",
"3",
")",
";",
"95",
"%",
"confidence",
"interval",
",",
"-",
"61.6",
"to",
"15.4",
";",
"P",
"=",
"0.001",
")",
".",
"Changes",
"in",
"total",
"body",
"fat",
"accounted",
"for",
"this",
"decrease",
".",
"Changes",
"in",
"dense",
"area",
"and",
"dense",
"volume",
",",
"measures",
"that",
"have",
"previously",
"been",
"associated",
"with",
"breast",
"cancer",
"risk",
",",
"were",
"not",
"significantly",
"different",
"between",
"the",
"groups",
"(",
"P",
">",
"or",
"=",
"0.26",
")",
".",
"Achieving",
"changes",
"in",
"mammographic",
"measures",
"may",
"require",
"more",
"exercise",
"or",
"a",
"study",
"population",
"with",
"higher",
"baseline",
"levels",
"of",
"sex",
"hormones",
"or",
"a",
"wider",
"range",
"of",
"mammographic",
"density",
".",
"The",
"data",
"from",
"this",
"study",
",",
"however",
",",
"suggest",
"that",
"the",
"protective",
"effect",
"of",
"exercise",
"on",
"breast",
"cancer",
"risk",
"may",
"operate",
"through",
"a",
"mechanism",
"other",
"than",
"mammographic",
"density",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
0,
7,
8,
8,
8,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
73 | [
"Perioperative",
"intravenous",
"lidocaine",
"decreases",
"the",
"incidence",
"of",
"persistent",
"pain",
"after",
"breast",
"surgery",
".",
"Breast",
"cancer",
"surgery",
"is",
"associated",
"with",
"a",
"high",
"incidence",
"of",
"persistent",
"postsurgical",
"pain",
"(",
"PPSP",
")",
".",
"The",
"aim",
"of",
"this",
"study",
"was",
"to",
"evaluate",
"the",
"impact",
"of",
"intravenous",
"(",
"IV",
")",
"lidocaine",
"on",
"acute",
"and",
"PPSP",
",",
"analgesic",
"requirements",
",",
"and",
"sensation",
"abnormalities",
"in",
"patients",
"undergoing",
"surgery",
"for",
"breast",
"cancer",
".",
"Thirty",
"-",
"six",
"patients",
"participated",
"in",
"this",
"randomized",
",",
"double",
"-",
"blinded",
"study",
".",
"Before",
"induction",
"of",
"general",
"anesthesia",
",",
"patients",
"received",
"a",
"bolus",
"of",
"intravenous",
"lidocaine",
"1.5",
"mg",
"/",
"kg",
"followed",
"by",
"a",
"continuous",
"infusion",
"of",
"lidocaine",
"1.5",
"mg",
"/",
"kgh",
"(",
"lidocaine",
"group",
")",
"or",
"an",
"equal",
"volume",
"of",
"saline",
"(",
"control",
"group",
")",
".",
"The",
"infusion",
"was",
"stopped",
"1",
"hour",
"after",
"the",
"skin",
"closure",
".",
"Pain",
"scores",
"and",
"analgesic",
"consumption",
"were",
"recorded",
"at",
"2",
",",
"4",
",",
"24",
"hours",
",",
"and",
"then",
"daily",
"for",
"1",
"week",
"postoperatively",
".",
"Three",
"months",
"later",
",",
"patients",
"were",
"assessed",
"for",
"PPSP",
"and",
"secondary",
"hyperalgesia",
".",
"Two",
"(",
"11.8",
"%",
")",
"patients",
"in",
"the",
"lidocaine",
"group",
"and",
"9",
"(",
"47.4",
"%",
")",
"patients",
"in",
"the",
"control",
"group",
"reported",
"PPSP",
"at",
"3",
"months",
"follow",
"-",
"up",
"(",
"P=",
"0.031",
")",
".",
"McGill",
"Pain",
"Questionnaire",
"revealed",
"greater",
"present",
"pain",
"intensity",
"-",
"visual",
"analog",
"scale",
"in",
"the",
"control",
"group",
"(",
"14.6",
"±",
"22.5",
"vs.",
"2.6",
"±",
"7.5",
";",
"P=",
"0.025",
")",
".",
"Secondary",
"hyperalgesia",
"(",
"area",
"of",
"hyperalgesia",
"/",
"length",
"of",
"surgical",
"incision",
")",
"was",
"significantly",
"less",
"in",
"the",
"lidocaine",
"group",
"compared",
"with",
"control",
"group",
"(",
"0.2",
"±",
"0.8",
"vs.",
"3.2",
"±",
"4.5",
"cm",
";",
"P=",
"0.002",
")",
".",
"The",
"2",
"groups",
"were",
"similar",
"in",
"terms",
"of",
"analgesic",
"consumption",
"during",
"the",
"early",
"postoperative",
"period",
".",
"Intravenous",
"perioperative",
"lidocaine",
"decreases",
"the",
"incidence",
"and",
"severity",
"of",
"PPSP",
"after",
"breast",
"cancer",
"surgery",
".",
"Prevention",
"of",
"the",
"induction",
"of",
"central",
"hyperalgesia",
"is",
"a",
"potential",
"mechanism",
"."
] | [
17,
18,
18,
0,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
13,
14,
14,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
27,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
33,
0,
41,
0,
35,
0,
43,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
41,
0,
35,
0,
43,
44,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
74 | [
"Impact",
"of",
"on",
"-",
"site",
"initiation",
"visits",
"on",
"patient",
"recruitment",
"and",
"data",
"quality",
"in",
"a",
"randomized",
"trial",
"of",
"adjuvant",
"chemotherapy",
"for",
"breast",
"cancer",
".",
"To",
"provide",
"empirical",
"evidence",
"on",
"the",
"impact",
"of",
"on",
"-",
"site",
"initiation",
"visits",
"on",
"the",
"following",
"outcomes",
":",
"patient",
"recruitment",
",",
"quantity",
"and",
"quality",
"of",
"data",
"submitted",
"to",
"the",
"trial",
"coordinating",
"office",
",",
"and",
"patients",
"'",
"follow",
"-",
"up",
"time",
".",
"This",
"methodological",
"study",
"was",
"performed",
"as",
"part",
"of",
"a",
"randomized",
"trial",
"comparing",
"two",
"combination",
"chemotherapies",
"for",
"adjuvant",
"treatment",
"of",
"breast",
"cancer",
".",
"Centers",
"participating",
"to",
"the",
"trial",
"were",
"randomized",
"to",
"either",
"receive",
"systematic",
"on",
"-",
"site",
"visits",
"(",
"Visited",
"group",
")",
",",
"or",
"not",
"(",
"Non",
"-",
"visited",
"group",
")",
".",
"The",
"study",
"was",
"terminated",
"after",
"two",
"years",
",",
"while",
"the",
"main",
"randomized",
"trial",
"continued",
".",
"Of",
"the",
"135",
"centers",
"that",
"had",
"expressed",
"an",
"interest",
"in",
"the",
"trial",
",",
"only",
"69",
"randomized",
"at",
"least",
"one",
"patient",
"(",
"35",
"/",
"68",
"in",
"the",
"Visited",
"group",
",",
"34",
"/",
"67",
"in",
"the",
"Non",
"-",
"visited",
"group",
")",
".",
"Almost",
"two",
"-",
"thirds",
"of",
"the",
"patients",
"were",
"entered",
"by",
"17",
"centers",
"(",
"10",
"in",
"the",
"Visited",
"group",
",",
"seven",
"in",
"the",
"Non",
"-",
"visited",
"group",
")",
"that",
"accrued",
"more",
"than",
"10",
"patients",
"each",
".",
"None",
"of",
"the",
"prespecified",
"outcomes",
"favored",
"the",
"group",
"of",
"centers",
"submitted",
"to",
"on",
"-",
"site",
"initiation",
"visits",
"(",
"ie",
",",
"mean",
"number",
"of",
"queries",
"par",
"patient",
":",
"6.1",
"+",
"/-",
"9.7",
"versus",
"5.4",
"+",
"/-",
"6.4",
",",
"respectively",
"for",
"the",
"Visited",
"and",
"Non",
"-",
"visited",
"groups",
")",
".",
"Spontaneous",
"transmittal",
"of",
"case",
"report",
"forms",
",",
"although",
"required",
"by",
"protocol",
",",
"was",
"low",
"in",
"both",
"randomized",
"groups",
"(",
"mean",
"number",
"of",
"pages",
"per",
"patient",
":",
"1.5",
"+",
"/-",
"2.0",
"versus",
"2.1",
"+",
"/-",
"2.3",
",",
"respectively",
")",
",",
"with",
"investigators",
"submitting",
"about",
"one",
"-",
"third",
"of",
"the",
"expected",
"forms",
"on",
"time",
"(",
"29",
"%",
"and",
"39",
"%",
",",
"respectively",
")",
".",
"This",
"study",
"could",
"not",
"evaluate",
"the",
"impact",
"of",
"repeated",
"on",
"-",
"site",
"visits",
"on",
"clinical",
"outcomes",
".",
"Systematic",
"on",
"-",
"site",
"initiation",
"visits",
"did",
"not",
"contribute",
"significantly",
"to",
"this",
"clinical",
"trial",
"."
] | [
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
33,
0,
0,
41,
0,
35,
0,
0,
43,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
0,
41,
0,
35,
0,
0,
43,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
75 | [
"Reducing",
"vasomotor",
"symptoms",
"with",
"acupuncture",
"in",
"breast",
"cancer",
"patients",
"treated",
"with",
"adjuvant",
"tamoxifen",
":",
"a",
"randomized",
"controlled",
"trial",
".",
"To",
"evaluate",
"true",
"acupuncture",
"to",
"control",
"acupuncture",
"(",
"CTRL",
")",
"(",
"non",
"-",
"insertive",
"stimulation",
"at",
"non",
"-",
"acupuncture",
"points",
")",
"in",
"breast",
"cancer",
"patients",
"treated",
"with",
"adjuvant",
"tamoxifen",
"suffering",
"from",
"hot",
"flushes",
"and",
"sweatings",
".",
"Eighty",
"-",
"four",
"patients",
"were",
"randomized",
"to",
"receive",
"either",
"true",
"acupuncture",
"or",
"CTRL",
"twice",
"a",
"week",
"for",
"5",
"weeks",
".",
"Seventy",
"-",
"four",
"patients",
"were",
"treated",
"according",
"to",
"the",
"protocol",
".",
"In",
"the",
"true",
"acupuncture",
"group",
"42",
"%",
"(",
"16",
"/",
"38",
")",
"reported",
"improvements",
"in",
"hot",
"flushes",
"after",
"6",
"weeks",
"compared",
"to",
"47",
"%",
"(",
"17",
"/",
"36",
")",
"in",
"the",
"CTRL",
"group",
"(",
"95",
"%",
"CI",
",",
"-",
"28",
"to",
"18",
"%",
")",
".",
"Both",
"groups",
"reported",
"improvement",
"regarding",
"severity",
"and",
"frequencies",
"in",
"hot",
"flushes",
"and",
"sweatings",
"but",
"no",
"statistical",
"difference",
"was",
"found",
"between",
"the",
"groups",
".",
"In",
"a",
"subanalysis",
"regarding",
"the",
"severity",
"of",
"sweatings",
"at",
"night",
"a",
"statistically",
"significant",
"difference",
"P",
"=",
"0.03",
"was",
"found",
"in",
"the",
"true",
"acupuncture",
"group",
".",
"Former",
"experience",
"of",
"true",
"acupuncture",
"did",
"not",
"influence",
"the",
"perception",
"of",
"true",
"acupuncture",
"or",
"CTRL",
".",
"No",
"significant",
"differences",
"in",
"hormonal",
"levels",
"were",
"found",
"before",
"and",
"after",
"treatment",
".",
"In",
"conclusion",
",",
"convincing",
"data",
"that",
"true",
"acupuncture",
"is",
"more",
"effective",
"than",
"CTRL",
"in",
"reducing",
"vasomotor",
"symptoms",
"is",
"still",
"lacking",
".",
"Our",
"study",
"shows",
"that",
"both",
"true",
"and",
"CTRL",
"reduce",
"vasomotor",
"symptoms",
"in",
"breast",
"cancer",
"patients",
"treated",
"with",
"adjuvant",
"tamoxifen",
"."
] | [
0,
0,
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
25,
0,
3,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
31,
32,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
76 | [
"Efficacy",
"and",
"safety",
"of",
"lipegfilgrastim",
"versus",
"pegfilgrastim",
":",
"a",
"randomized",
",",
"multicenter",
",",
"active",
"-",
"control",
"phase",
"3",
"trial",
"in",
"patients",
"with",
"breast",
"cancer",
"receiving",
"doxorubicin",
"/",
"docetaxel",
"chemotherapy",
".",
"Lipegfilgrastim",
"is",
"a",
"novel",
"glyco",
"-",
"pegylated",
"granulocyte",
"-",
"colony",
"stimulating",
"factor",
"in",
"development",
"for",
"neutropenia",
"prophylaxis",
"in",
"cancer",
"patients",
"receiving",
"chemotherapy",
".",
"This",
"phase",
"III",
",",
"double",
"-",
"blind",
",",
"randomized",
",",
"active",
"-",
"controlled",
",",
"noninferiority",
"trial",
"compared",
"the",
"efficacy",
"and",
"safety",
"of",
"lipegfilgrastim",
"versus",
"pegfilgrastim",
"in",
"chemotherapy",
"-",
"naïve",
"breast",
"cancer",
"patients",
"receiving",
"doxorubicin",
"/",
"docetaxel",
"chemotherapy",
".",
"Patients",
"with",
"high",
"-",
"risk",
"stage",
"II",
",",
"III",
",",
"or",
"IV",
"breast",
"cancer",
"and",
"an",
"absolute",
"neutrophil",
"count",
"≥",
"1.5",
"×",
"109",
"cells",
"/",
"L",
"were",
"randomized",
"to",
"a",
"single",
"6",
"-mg",
"subcutaneous",
"injection",
"of",
"lipegfilgrastim",
"(",
"n",
"=",
"101",
")",
"or",
"pegfilgrastim",
"(",
"n",
"=",
"101",
")",
"on",
"day",
"2",
"of",
"each",
"21",
"-day",
"chemotherapy",
"cycle",
"(",
"4",
"cycles",
"maximum",
")",
".",
"The",
"primary",
"efficacy",
"endpoint",
"was",
"the",
"duration",
"of",
"severe",
"neutropenia",
"during",
"cycle",
"1",
".",
"Cycle",
"1",
":",
"The",
"mean",
"duration",
"of",
"severe",
"neutropenia",
"for",
"the",
"lipegfilgrastim",
"and",
"pegfilgrastim",
"groups",
"was",
"0.7",
"and",
"0.8",
"days",
",",
"respectively",
"(",
"λ",
"=",
"-",
"0.218",
"[",
"95",
"%",
"confidence",
"interval",
":",
"-",
"0.498",
"%",
",",
"0.062",
"%",
"]",
",",
"p",
"=",
"0.126",
")",
",",
"and",
"no",
"severe",
"neutropenia",
"was",
"observed",
"in",
"56",
"%",
"and",
"49",
"%",
"of",
"patients",
"in",
"the",
"lipegfilgrastim",
"and",
"pegfilgrastim",
"groups",
",",
"respectively",
".",
"All",
"cycles",
":",
"In",
"the",
"efficacy",
"population",
",",
"febrile",
"neutropenia",
"occurred",
"in",
"three",
"pegfilgrastim",
"-",
"treated",
"patients",
"(",
"all",
"in",
"cycle",
"1",
")",
"and",
"zero",
"lipegfilgrastim",
"-",
"treated",
"patients",
".",
"Drug",
"-",
"related",
"adverse",
"events",
"in",
"the",
"safety",
"population",
"were",
"reported",
"in",
"28",
"%",
"and",
"26",
"%",
"of",
"patients",
"in",
"the",
"lipegfilgrastim",
"and",
"pegfilgrastim",
"groups",
",",
"respectively",
".",
"This",
"study",
"demonstrates",
"that",
"lipegfilgrastim",
"6",
"mg",
"is",
"as",
"effective",
"as",
"pegfilgrastim",
"in",
"reducing",
"neutropenia",
"in",
"patients",
"with",
"breast",
"cancer",
"receiving",
"myelosuppressive",
"chemotherapy",
".",
"Eudra",
"EEACTA",
"200901599910",
"."
] | [
0,
0,
0,
0,
17,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
33,
0,
35,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
77 | [
"Genetically",
"Predicted",
"Body",
"Mass",
"Index",
"and",
"Breast",
"Cancer",
"Risk",
":",
"Mendelian",
"Randomization",
"Analyses",
"of",
"Data",
"from",
"145",
",",
"000",
"Women",
"of",
"European",
"Descent",
".",
"Observational",
"epidemiological",
"studies",
"have",
"shown",
"that",
"high",
"body",
"mass",
"index",
"(",
"BMI",
")",
"is",
"associated",
"with",
"a",
"reduced",
"risk",
"of",
"breast",
"cancer",
"in",
"premenopausal",
"women",
"but",
"an",
"increased",
"risk",
"in",
"postmenopausal",
"women",
".",
"It",
"is",
"unclear",
"whether",
"this",
"association",
"is",
"mediated",
"through",
"shared",
"genetic",
"or",
"environmental",
"factors",
".",
"We",
"applied",
"Mendelian",
"randomization",
"to",
"evaluate",
"the",
"association",
"between",
"BMI",
"and",
"risk",
"of",
"breast",
"cancer",
"occurrence",
"using",
"data",
"from",
"two",
"large",
"breast",
"cancer",
"consortia",
".",
"We",
"created",
"a",
"weighted",
"BMI",
"genetic",
"score",
"comprising",
"84",
"BMI",
"-",
"associated",
"genetic",
"variants",
"to",
"predicted",
"BMI",
".",
"We",
"evaluated",
"genetically",
"predicted",
"BMI",
"in",
"association",
"with",
"breast",
"cancer",
"risk",
"using",
"individual",
"-",
"level",
"data",
"from",
"the",
"Breast",
"Cancer",
"Association",
"Consortium",
"(",
"BCAC",
")",
"(",
"cases",
"=",
"46",
",",
"325",
",",
"controls",
"=",
"42",
",",
"482",
")",
".",
"We",
"further",
"evaluated",
"the",
"association",
"between",
"genetically",
"predicted",
"BMI",
"and",
"breast",
"cancer",
"risk",
"using",
"summary",
"statistics",
"from",
"16",
",",
"003",
"cases",
"and",
"41",
",",
"335",
"controls",
"from",
"the",
"Discovery",
",",
"Biology",
",",
"and",
"Risk",
"of",
"Inherited",
"Variants",
"in",
"Breast",
"Cancer",
"(",
"DRIVE",
")",
"Project",
".",
"Because",
"most",
"studies",
"measured",
"BMI",
"after",
"cancer",
"diagnosis",
",",
"we",
"could",
"not",
"conduct",
"a",
"parallel",
"analysis",
"to",
"adequately",
"evaluate",
"the",
"association",
"of",
"measured",
"BMI",
"with",
"breast",
"cancer",
"risk",
"prospectively",
".",
"In",
"the",
"BCAC",
"data",
",",
"genetically",
"predicted",
"BMI",
"was",
"found",
"to",
"be",
"inversely",
"associated",
"with",
"breast",
"cancer",
"risk",
"(",
"odds",
"ratio",
"[",
"OR",
"]",
"=",
"0.65",
"per",
"5",
"kg",
"/",
"m",
"2",
"increase",
",",
"95",
"%",
"confidence",
"interval",
"[",
"CI",
"]",
":",
"0.56",
"-",
"0.75",
",",
"p",
"=",
"3.32",
"×",
"10",
"-",
"10",
")",
".",
"The",
"associations",
"were",
"similar",
"for",
"both",
"premenopausal",
"(",
"OR",
"=",
"0.44",
",",
"95",
"%",
"CI:",
"0.31",
"-",
"0.62",
",",
"p",
"=",
"9.91",
"×",
"10",
"-",
"8",
")",
"and",
"postmenopausal",
"breast",
"cancer",
"(",
"OR",
"=",
"0.57",
",",
"95",
"%",
"CI",
":",
"0.46",
"-",
"0.71",
",",
"p",
"=",
"1.88",
"×",
"10",
"-",
"8",
")",
".",
"This",
"association",
"was",
"replicated",
"in",
"the",
"data",
"from",
"the",
"DRIVE",
"consortium",
"(",
"OR",
"=",
"0.72",
",",
"95",
"%",
"CI",
":",
"0.60",
"-",
"0.84",
",",
"p",
"=",
"1.64",
"×",
"10",
"-",
"7",
")",
".",
"Single",
"marker",
"analyses",
"identified",
"17",
"of",
"the",
"84",
"BMI",
"-",
"associated",
"single",
"nucleotide",
"polymorphisms",
"(",
"SNPs",
")",
"in",
"association",
"with",
"breast",
"cancer",
"risk",
"at",
"p",
"<",
"0.05",
";",
"for",
"16",
"of",
"them",
",",
"the",
"allele",
"associated",
"with",
"elevated",
"BMI",
"was",
"associated",
"with",
"reduced",
"breast",
"cancer",
"risk",
".",
"BMI",
"predicted",
"by",
"genome",
"-",
"wide",
"association",
"studies",
"(",
"GWAS",
")",
"-identified",
"variants",
"is",
"inversely",
"associated",
"with",
"the",
"risk",
"of",
"both",
"pre-",
"and",
"postmenopausal",
"breast",
"cancer",
".",
"The",
"reduced",
"risk",
"of",
"postmenopausal",
"breast",
"cancer",
"associated",
"with",
"genetically",
"predicted",
"BMI",
"observed",
"in",
"this",
"study",
"differs",
"from",
"the",
"positive",
"association",
"reported",
"from",
"studies",
"using",
"measured",
"adult",
"BMI",
".",
"Understanding",
"the",
"reasons",
"for",
"this",
"discrepancy",
"may",
"reveal",
"insights",
"into",
"the",
"complex",
"relationship",
"of",
"genetic",
"determinants",
"of",
"body",
"weight",
"in",
"the",
"etiology",
"of",
"breast",
"cancer",
"."
] | [
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
4,
4,
4,
0,
19,
0,
6,
6,
6,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
78 | [
"Phase",
"III",
"study",
"of",
"letrozole",
"versus",
"tamoxifen",
"as",
"first",
"-",
"line",
"therapy",
"of",
"advanced",
"breast",
"cancer",
"in",
"postmenopausal",
"women",
":",
"analysis",
"of",
"survival",
"and",
"update",
"of",
"efficacy",
"from",
"the",
"International",
"Letrozole",
"Breast",
"Cancer",
"Group",
".",
"To",
"analyze",
"overall",
"survival",
"(",
"OS",
")",
"and",
"update",
"efficacy",
"data",
"for",
"letrozole",
"versus",
"tamoxifen",
"as",
"first",
"-",
"line",
"therapy",
"in",
"postmenopausal",
"women",
"with",
"locally",
"advanced",
"or",
"metastatic",
"breast",
"cancer",
".",
"This",
"multicenter",
"phase",
"III",
"trial",
"randomly",
"assigned",
"916",
"patients",
"with",
"hormone",
"receptor",
"-",
"positive",
"or",
"unknown",
"tumors",
"letrozole",
"2.5",
"mg",
"(",
"n",
"=",
"458",
")",
"or",
"tamoxifen",
"20",
"mg",
"(",
"n",
"=",
"458",
")",
"daily",
"until",
"disease",
"progression",
".",
"Optional",
"cross",
"-",
"over",
"was",
"permitted",
"at",
"the",
"treating",
"physician",
"'s",
"discretion",
".",
"This",
"report",
"updates",
"efficacy",
"at",
"a",
"median",
"follow",
"-",
"up",
"of",
"32",
"months",
".",
"The",
"superiority",
"of",
"letrozole",
"to",
"tamoxifen",
"was",
"confirmed",
"for",
"time",
"to",
"progression",
"(",
"median",
",",
"9.4",
"v",
"6.0",
"months",
",",
"respectively",
";",
"P",
"<",
".",
"0001",
")",
",",
"time",
"to",
"treatment",
"failure",
"(",
"median",
",",
"9",
"v",
"5.7",
"months",
",",
"respectively",
";",
"P",
"<",
".",
"0001",
")",
",",
"overall",
"objective",
"response",
"rate",
"(",
"32",
"%",
"v",
"21",
"%",
",",
"respectively",
";",
"P",
"=",
".",
"0002",
")",
",",
"and",
"overall",
"clinical",
"benefit",
".",
"Median",
"OS",
"was",
"slightly",
"prolonged",
"for",
"the",
"randomized",
"letrozole",
"arm",
"(",
"34",
"v",
"30",
"months",
",",
"respectively",
")",
".",
"Although",
"this",
"difference",
"in",
"OS",
"is",
"not",
"significant",
",",
"survival",
"was",
"improved",
"in",
"the",
"randomized",
"letrozole",
"arm",
"over",
"the",
"first",
"2",
"years",
"of",
"the",
"study",
".",
"Approximately",
"one",
"half",
"of",
"the",
"patients",
"in",
"each",
"arm",
"crossed",
"over",
".",
"Total",
"duration",
"of",
"endocrine",
"therapy",
"(",
"\"",
"time",
"to",
"chemotherapy",
"\"",
")",
"was",
"significantly",
"longer",
"(",
"P",
"=",
".",
"005",
")",
"for",
"patients",
"initially",
"on",
"letrozole",
"(",
"median",
",",
"16",
"months",
")",
"than",
"for",
"patients",
"initially",
"on",
"tamoxifen",
"(",
"median",
",",
"9",
"months",
")",
".",
"Time",
"to",
"worsening",
"of",
"Karnofsky",
"performance",
"score",
"was",
"significantly",
"delayed",
"with",
"letrozole",
"compared",
"with",
"tamoxifen",
"(",
"P",
"=",
".",
"001",
")",
".",
"This",
"study",
"documents",
"the",
"superiority",
"of",
"letrozole",
"over",
"tamoxifen",
"in",
"first",
"-",
"line",
"endocrine",
"therapy",
"in",
"postmenopausal",
"women",
"with",
"advanced",
"breast",
"cancer",
"."
] | [
0,
0,
0,
0,
17,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
37,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
37,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
37,
0,
39,
40,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
37,
38,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
39,
40,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
79 | [
"Treatment",
"with",
"Ruta",
"graveolens",
"5",
"CH",
"and",
"Rhus",
"toxicodendron",
"9",
"CH",
"may",
"reduce",
"joint",
"pain",
"and",
"stiffness",
"linked",
"to",
"aromatase",
"inhibitors",
"in",
"women",
"with",
"early",
"breast",
"cancer",
":",
"results",
"of",
"a",
"pilot",
"observational",
"study",
".",
"To",
"determine",
"the",
"possible",
"effect",
"of",
"two",
"homeopathic",
"medicines",
",",
"Ruta",
"graveolens",
"5",
"CH",
"and",
"Rhus",
"toxicodendron",
"9",
"CH",
",",
"in",
"the",
"prevention",
"of",
"aromatase",
"inhibitor",
"(",
"AI",
")",
"associated",
"joint",
"pain",
"and/or",
"stiffness",
"in",
"women",
"with",
"early",
",",
"hormone",
"-",
"receptor",
"positive",
",",
"breast",
"cancer",
".",
"This",
"prospective",
",",
"unrandomized",
"observational",
"study",
"was",
"carried",
"out",
"between",
"April",
"and",
"October",
"2014",
".",
"Women",
"were",
"recruited",
"in",
"two",
"groups",
",",
"according",
"to",
"which",
"of",
"the",
"two",
"study",
"centres",
"they",
"attended",
":",
"one",
"receiving",
"homeopathy",
"in",
"addition",
"to",
"standard",
"treatment",
"(",
"group",
"H",
")",
"and",
"a",
"control",
"group",
",",
"receiving",
"standard",
"treatment",
"(",
"group",
"C",
")",
".",
"All",
"women",
"were",
"treated",
"with",
"an",
"AI",
".",
"In",
"addition",
",",
"women",
"in",
"group",
"H",
"also",
"took",
"Ruta",
"graveolens",
"5",
"CH",
"and",
"Rhus",
"toxicodendron",
"9",
"CH",
"(",
"5",
"granules",
",",
"twice",
"a",
"day",
")",
"up",
"to",
"7",
"days",
"before",
"starting",
"AI",
"treatment",
".",
"The",
"homeopathic",
"medicines",
"were",
"continued",
"for",
"3",
"months",
".",
"Demographic",
"and",
"clinical",
"data",
"were",
"recorded",
"using",
"a",
"self",
"-",
"assessment",
"questionnaire",
"at",
"inclusion",
"(",
"T",
"0",
")",
"and",
"3",
"months",
"(",
"T",
"3",
")",
".",
"Primary",
"evaluation",
"criteria",
"were",
"the",
"evolution",
"of",
"scores",
"for",
"joint",
"pain",
"and",
"stiffness",
",",
"the",
"impact",
"of",
"pain",
"on",
"sleep",
"and",
"analgesic",
"consumption",
"in",
"the",
"two",
"groups",
"after",
"3",
"months",
"of",
"treatment",
".",
"Forty",
"patients",
"(",
"mean",
"age",
"64.9",
"±",
"8.1",
"years",
")",
"were",
"recruited",
",",
"20",
"in",
"each",
"group",
".",
"Two",
"-",
"thirds",
"of",
"the",
"patients",
"had",
"joint",
"pain",
"before",
"starting",
"AI",
"treatment",
".",
"There",
"was",
"a",
"significant",
"difference",
"in",
"the",
"evolution",
"of",
"mean",
"composite",
"pain",
"score",
"between",
"T",
"0",
"and",
"T",
"3",
"in",
"the",
"two",
"groups",
"(",
"-",
"1.3",
"in",
"group",
"H",
"vs.",
"+",
"3.4",
"in",
"group",
"C",
";",
"p=",
"0.0001",
")",
".",
"The",
"individual",
"components",
"of",
"the",
"pain",
"score",
"(",
"frequency",
",",
"intensity",
"and",
"number",
"of",
"sites",
"of",
"pain",
")",
"also",
"decreased",
"significantly",
"in",
"group",
"H",
".",
"Nine",
"patients",
"in",
"group",
"C",
"(",
"45",
"%",
")",
"vs.",
"1",
"(",
"5",
"%",
")",
"in",
"group",
"H",
"increased",
"their",
"analgesic",
"consumption",
"between",
"T",
"0",
"and",
"T",
"3",
"(",
"p=",
"0.0076",
")",
".",
"After",
"3",
"months",
"of",
"treatment",
",",
"joint",
"pain",
"had",
"a",
"worse",
"impact",
"on",
"sleep",
"in",
"patients",
"in",
"group",
"C",
"(",
"35",
"%",
"vs.",
"0",
"%",
"of",
"patients",
";",
"p=",
"0.0083",
")",
".",
"The",
"differences",
"observed",
"in",
"the",
"evolution",
"of",
"morning",
"and",
"daytime",
"stiffness",
"between",
"the",
"two",
"groups",
"were",
"smaller",
"(",
"p=",
"0.053",
"and",
"p=",
"0.33",
",",
"respectively",
")",
",",
"with",
"the",
"exception",
"of",
"time",
"necessary",
"for",
"the",
"disappearance",
"of",
"morning",
"stiffness",
"which",
"was",
"greater",
"in",
"group",
"C",
"(",
"37.7",
"±",
"23.0",
"vs.",
"17.9",
"±",
"20.1",
"min",
";",
"p=",
"0.0173",
")",
".",
"These",
"preliminary",
"results",
"suggest",
"that",
"treatment",
"with",
"Ruta",
"graveolens",
"5",
"CH",
"and",
"Rhus",
"toxicodendron",
"9",
"CH",
"may",
"decrease",
"joint",
"pain",
"/",
"stiffness",
"in",
"breast",
"cancer",
"patients",
"treated",
"with",
"AIs",
".",
"A",
"larger",
"-",
"scale",
"randomized",
"study",
"is",
"required",
"to",
"confirm",
"these",
"results",
"."
] | [
0,
0,
17,
18,
18,
18,
18,
18,
18,
18,
18,
0,
0,
13,
14,
14,
14,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
34,
0,
0,
0,
0,
35,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
31,
32,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
31,
32,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
41,
0,
35,
0,
43,
44,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
80 | [
"Randomized",
"trial",
"of",
"fenretinide",
"to",
"prevent",
"second",
"breast",
"malignancy",
"in",
"women",
"with",
"early",
"breast",
"cancer",
".",
"Fenretinide",
",",
"a",
"vitamin",
"A",
"analogue",
",",
"has",
"been",
"shown",
"to",
"inhibit",
"breast",
"carcinogenesis",
"in",
"preclinical",
"studies",
".",
"We",
"determined",
"the",
"efficacy",
"of",
"fenretinide",
"in",
"preventing",
"a",
"second",
"breast",
"malignancy",
"in",
"women",
"with",
"breast",
"cancer",
".",
"We",
"randomly",
"assigned",
"2972",
"women",
",",
"aged",
"30",
"-",
"70",
"years",
",",
"with",
"surgically",
"removed",
"stage",
"I",
"breast",
"cancer",
"or",
"ductal",
"carcinoma",
"in",
"situ",
"to",
"receive",
"for",
"5",
"years",
"either",
"fenretinide",
"orally",
"(",
"200",
"mg",
"/",
"day",
")",
"or",
"no",
"treatment",
".",
"The",
"primary",
"end",
"point",
"was",
"the",
"incidence",
"of",
"contralateral",
"breast",
"cancer",
"or",
"ipsilateral",
"breast",
"cancer",
"7",
"years",
"after",
"randomization",
".",
"Other",
"end",
"points",
"considered",
"post",
"hoc",
"were",
"the",
"same",
"outcomes",
"stratified",
"by",
"menopausal",
"status",
",",
"incidence",
"of",
"distant",
"metastases",
",",
"overall",
"mortality",
",",
"and",
"tumors",
"in",
"other",
"organs",
".",
"The",
"hazards",
"of",
"breast",
"cancer",
"occurrence",
"were",
"determined",
"by",
"Cox",
"proportional",
"hazards",
"regression",
"analysis",
".",
"Statistical",
"tests",
"were",
"two",
"-",
"sided",
".",
"At",
"a",
"median",
"observation",
"time",
"of",
"97",
"months",
",",
"there",
"were",
"no",
"statistically",
"significant",
"differences",
"in",
"the",
"occurrence",
"of",
"contralateral",
"breast",
"cancer",
"(",
"P",
"=",
".",
"642",
")",
"or",
"ipsilateral",
"breast",
"cancer",
"(",
"P",
"=",
".",
"177",
")",
"between",
"the",
"two",
"arms",
".",
"However",
",",
"an",
"interaction",
"was",
"detected",
"between",
"fenretinide",
"treatment",
"and",
"menopausal",
"status",
"in",
"both",
"outcomes",
"(",
"P",
"for",
"interaction",
"in",
"both",
"outcomes",
"=",
".",
"045",
")",
",",
"with",
"a",
"possible",
"beneficial",
"effect",
"in",
"premenopausal",
"women",
"(",
"contralateral",
"breast",
"cancer",
":",
"adjusted",
"hazard",
"ratio",
"[",
"HR",
"]",
"=",
"0.66",
",",
"and",
"95",
"%",
"confidence",
"interval",
"[",
"CI",
"]",
"=",
"0.41",
"-",
"1.07",
";",
"ipsilateral",
"breast",
"cancer",
":",
"adjusted",
"HR",
"=",
"0.65",
",",
"and",
"95",
"%",
"CI",
"=",
"0.46",
"-",
"0",
".",
"92",
")",
"and",
"an",
"opposite",
"effect",
"in",
"postmenopausal",
"women",
"(",
"contralateral",
"breast",
"cancer",
":",
"adjusted",
"HR",
"=",
"1.32",
",",
"and",
"95",
"%",
"CI",
"=",
"0.82",
"-",
"2.15",
";",
"ipsilateral",
"breast",
"cancer",
":",
"adjusted",
"HR",
"=",
"1.19",
",",
"and",
"95",
"%",
"CI",
"=",
"0.75",
"-",
"1",
".",
"89",
")",
".",
"There",
"were",
"no",
"statistically",
"significant",
"differences",
"between",
"the",
"two",
"arms",
"in",
"tumors",
"in",
"other",
"organs",
",",
"incidence",
"of",
"distant",
"metastasis",
",",
"and",
"all",
"-",
"cause",
"mortality",
".",
"Fenretinide",
"treatment",
"of",
"women",
"with",
"breast",
"cancer",
"for",
"5",
"years",
"appears",
"to",
"have",
"no",
"statistically",
"significant",
"effect",
"on",
"the",
"incidence",
"of",
"second",
"breast",
"malignancies",
"overall",
",",
"although",
"a",
"possible",
"benefit",
"was",
"detected",
"in",
"premenopausal",
"women",
".",
"These",
"studies",
",",
"particularly",
"the",
"post",
"hoc",
"analyses",
",",
"are",
"considered",
"exploratory",
"and",
"need",
"to",
"be",
"confirmed",
"."
] | [
0,
0,
0,
17,
0,
0,
13,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
7,
8,
8,
8,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
0,
23,
24,
24,
24,
0,
23,
24,
0,
0,
23,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
21,
22,
22,
22,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
81 | [
"High",
"-",
"dose",
"oral",
"medroxyprogesterone",
"acetate",
"or",
"tamoxifen",
"as",
"adjuvant",
"hormone",
"therapy",
"for",
"node",
"-",
"negative",
"early",
"-",
"stage",
"breast",
"cancer",
":",
"randomized",
"trial",
"with",
"7",
"-year",
"update",
".",
"A",
"randomized",
"adjuvant",
"trial",
"compared",
"tamoxifen",
"20",
"mg",
"daily",
"for",
"5",
"years",
"with",
"high",
"-",
"dose",
"oral",
"medroxyprogesterone",
"acetate",
"(",
"MPA",
")",
"1",
"g",
"orally",
"for",
"9",
"months",
".",
"One",
"hundred",
"ninety",
"-",
"four",
"patients",
"with",
"histologically",
"proven",
"primary",
"node",
"-",
"negative",
"breast",
"carcinoma",
"were",
"enrolled",
"between",
"December",
"1990",
"and",
"October",
"1996",
",",
"with",
"98",
"patients",
"randomized",
"into",
"the",
"tamoxifen",
"arm",
"and",
"96",
"into",
"the",
"MPA",
"arm",
".",
"At",
"a",
"median",
"follow",
"-",
"up",
"of",
"86",
"months",
",",
"25",
"relapses",
"and",
"13",
"deaths",
"were",
"recorded",
".",
"The",
"relapse",
"-",
"free",
"survival",
"rate",
"at",
"7",
"years",
"in",
"the",
"tamoxifen",
"arm",
"was",
"93",
"%",
",",
"versus",
"81",
"%",
"in",
"the",
"MPA",
"arm",
"(",
"P",
"=",
"0.02",
")",
".",
"The",
"difference",
"was",
"observed",
"in",
"patients",
"with",
"stage",
"T",
"2",
"disease",
"(",
"100",
"%",
"in",
"the",
"tamoxifen",
"group",
"vs.",
"64",
"%",
"in",
"the",
"MPA",
"group",
";",
"P",
"=",
"0.01",
")",
",",
"in",
"younger",
"and/or",
"premenopausal",
"patients",
"(",
"in",
"patients",
"<",
"50",
"years",
"of",
"age",
",",
"100",
"%",
"in",
"the",
"tamoxifen",
"arm",
"vs.",
"81",
"%",
"in",
"the",
"MPA",
"arm",
"[",
"P",
"=",
"0.02",
"]",
",",
"and",
"in",
"patients",
">",
"or",
"=",
"50",
"years",
"of",
"age",
",",
"90",
"%",
"in",
"the",
"tamoxifen",
"arm",
"vs.",
"82",
"%",
"in",
"the",
"MPA",
"arm",
"[",
"P",
"=",
"0.16",
"]",
")",
".",
"Also",
",",
"the",
"overall",
"survival",
"rate",
"at",
"7",
"years",
"was",
"lower",
"in",
"women",
"<",
"50",
"years",
"of",
"age",
"(",
"P",
"=",
"0.04",
")",
"."
] | [
19,
20,
20,
20,
20,
20,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
2,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
21,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
29,
30,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
82 | [
"Randomized",
"Controlled",
"Trial",
"of",
"Zoledronic",
"Acid",
"plus",
"Chemotherapy",
"versus",
"Chemotherapy",
"Alone",
"as",
"Neoadjuvant",
"Treatment",
"of",
"HER",
"2",
"-",
"Negative",
"Primary",
"Breast",
"Cancer",
"(",
"JONIE",
"Study",
")",
".",
"Zoledronic",
"acid",
"(",
"ZOL",
")",
"is",
"a",
"nitrogen",
"-",
"containing",
"bisphosphonate",
"that",
"induces",
"osteoclast",
"apoptosis",
"and",
"inhibits",
"bone",
"resorption",
"by",
"inhibiting",
"the",
"mevalonate",
"pathway",
".",
"Its",
"benefit",
"for",
"the",
"prevention",
"of",
"skeletal",
"complications",
"due",
"to",
"bone",
"metastases",
"has",
"been",
"established",
".",
"However",
",",
"the",
"antitumor",
"efficacy",
"of",
"ZOL",
",",
"although",
"suggested",
"by",
"multiple",
"preclinical",
"and",
"clinical",
"studies",
",",
"has",
"not",
"yet",
"been",
"clinically",
"proven",
".",
"We",
"performed",
"the",
"present",
"randomized",
"Phase",
"2",
"trial",
"to",
"investigate",
"the",
"antitumor",
"effect",
"of",
"ZOL",
"with",
"chemotherapy",
"(",
"CT",
")",
".",
"Asian",
"patients",
"with",
"HER",
"2",
"-",
"negative",
"invasive",
"breast",
"cancer",
"were",
"randomly",
"assigned",
"to",
"either",
"the",
"CT",
"or",
"CT+ZOL",
"(",
"CTZ",
")",
"group",
".",
"One",
"hundred",
"and",
"eighty",
"-",
"eight",
"patients",
"were",
"randomized",
"to",
"either",
"the",
"CT",
"group",
"(",
"n",
"=",
"95",
")",
"or",
"the",
"CTZ",
"group",
"(",
"n",
"=",
"93",
")",
"from",
"March",
"2010",
"to",
"April",
"2012",
",",
"and",
"180",
"patients",
"were",
"assessed",
".",
"All",
"patients",
"received",
"four",
"cycles",
"of",
"FEC",
"100",
"(",
"fluorouracil",
"500",
"mg",
"/",
"m",
"2",
",",
"epirubicin",
"100",
"mg",
"/",
"m",
"2",
",",
"and",
"cyclophosphamide",
"500",
"mg",
"/",
"m",
"2",
")",
",",
"followed",
"by",
"12",
"cycles",
"of",
"paclitaxel",
"at",
"80",
"mg",
"/",
"m",
"2",
"weekly",
".",
"ZOL",
"(",
"4",
"mg",
")",
"was",
"administered",
"three",
"to",
"four",
"times",
"weekly",
"for",
"7",
"weeks",
"to",
"the",
"patients",
"in",
"the",
"CTZ",
"group",
".",
"The",
"primary",
"endpoint",
"was",
"the",
"pathological",
"complete",
"response",
"(",
"pCR",
")",
"rate",
",",
"which",
"was",
"defined",
"as",
"no",
"invasive",
"cancer",
"in",
"the",
"breast",
"tissue",
"specimen",
".",
"Safety",
"was",
"assessed",
"in",
"all",
"patients",
"who",
"received",
"at",
"least",
"one",
"dose",
"of",
"the",
"study",
"drug",
".",
"This",
"randomized",
"controlled",
"trial",
"indicated",
"that",
"the",
"rates",
"of",
"pCR",
"in",
"CTZ",
"group",
"(",
"14.8",
"%",
")",
"was",
"doubled",
"to",
"CT",
"group",
"(",
"7.7",
"%",
")",
",",
"respectively",
"(",
"one",
"-",
"sided",
"chi",
"-",
"square",
"test",
",",
"p",
"=",
"0.068",
")",
",",
"though",
"the",
"additional",
"efficacy",
"of",
"zoledronic",
"acid",
"was",
"not",
"demonstrated",
"statistically",
".",
"The",
"pCR",
"rate",
"in",
"postmenopausal",
"patients",
"was",
"18.4",
"%",
"and",
"5.1",
"%",
"in",
"the",
"CTZ",
"and",
"CT",
"groups",
",",
"respectively",
"(",
"one",
"-",
"sided",
"Fisher",
"'s",
"exact",
"test",
",",
"p",
"=",
"0.071",
")",
",",
"and",
"that",
"in",
"patients",
"with",
"triple",
"-",
"negative",
"breast",
"cancer",
"was",
"35.3",
"%",
"and",
"11.8",
"%",
"in",
"the",
"CTZ",
"and",
"CT",
"groups",
",",
"respectively",
"(",
"one",
"-",
"sided",
"Fisher",
"'s",
"exact",
"test",
",",
"p",
"=",
"0.112",
")",
".",
"Thus",
"the",
"addition",
"of",
"ZOL",
"to",
"neoadjuvant",
"CT",
"has",
"potential",
"anticancer",
"benefits",
"in",
"postmenopausal",
"patients",
"and",
"patients",
"with",
"triple",
"-",
"negative",
"breast",
"cancer",
".",
"Further",
"investigation",
"is",
"warranted",
".",
"University",
"Hospital",
"Medical",
"Information",
"Network",
".",
"UMIN",
"000003261",
"."
] | [
0,
0,
0,
0,
17,
18,
18,
18,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
9,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
2,
2,
2,
2,
2,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
21,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
83 | [
"Weekly",
"docetaxel",
"versus",
"CMF",
"as",
"adjuvant",
"chemotherapy",
"for",
"elderly",
"breast",
"cancer",
"patients",
":",
"safety",
"data",
"from",
"the",
"multicentre",
"phase",
"3",
"randomised",
"ELDA",
"trial",
".",
"Within",
"an",
"ongoing",
"multicentre",
"phase",
"3",
"randomised",
"trial",
"(",
"ELDA",
",",
"cancertrials",
".",
"gov",
"ID",
":",
"NCT",
"00331097",
")",
",",
"early",
"breast",
"cancer",
"patients",
",",
"65",
"-",
"79",
"years",
"old",
",",
"with",
"average",
"to",
"high",
"risk",
"of",
"recurrence",
",",
"are",
"randomly",
"assigned",
"to",
"receive",
"CMF",
"(",
"cyclophosphamide",
"600",
"mg",
"/",
"m",
"2",
",",
"methotrexate",
"40",
"mg",
"/",
"m",
"2",
",",
"fluorouracil",
"600",
"mg",
"/",
"m",
"2",
",",
"days",
"1",
"-",
"8",
")",
"or",
"docetaxel",
"(",
"35",
"mg",
"/",
"m",
"2",
"days",
"1",
"-",
"8",
"-",
"15",
")",
",",
"every",
"4",
"weeks",
".",
"Here",
"we",
"report",
"an",
"unplanned",
"safety",
"analysis",
"prompted",
"by",
"an",
"amendment",
"introducing",
"creatinine",
"clearance",
"as",
"a",
"tool",
"to",
"adjust",
"methotrexate",
"dose",
".",
"Before",
"such",
"change",
",",
"101",
"patients",
"with",
"a",
"median",
"age",
"of",
"70",
"were",
"randomly",
"assigned",
"CMF",
"(",
"53",
"patients",
")",
"or",
"docetaxel",
"(",
"48",
"patients",
")",
".",
"At",
"least",
"one",
"grades",
"3",
"-",
"4",
"toxic",
"event",
"of",
"any",
"type",
"was",
"reported",
"in",
"40",
"(",
"75.5",
"%",
")",
"and",
"19",
"(",
"39.6",
"%",
")",
"patients",
"with",
"CMF",
"and",
"docetaxel",
",",
"respectively",
"(",
"p=",
"0.0002",
")",
".",
"Grades",
"3",
"-",
"4",
"hematological",
"events",
"were",
"observed",
"in",
"37",
"(",
"69.8",
"%",
")",
"vs.",
"4",
"(",
"8.3",
"%",
")",
"cases",
"(",
"p",
"<",
"0.0001",
")",
"and",
"grades",
"3",
"-",
"4",
"non",
"-",
"hematological",
"toxicity",
"in",
"12",
"(",
"22.6",
"%",
")",
"vs.",
"15",
"(",
"31.2",
"%",
")",
"patients",
"(",
"p=",
"0.11",
")",
",",
"with",
"CMF",
"and",
"docetaxel",
",",
"respectively",
".",
"A",
"higher",
"incidence",
"of",
"anemia",
",",
"neutropenia",
",",
"thrombocytopenia",
"and",
"febrile",
"neutropenia",
"was",
"reported",
"with",
"CMF",
".",
"Constipation",
",",
"mucositis",
",",
"nausea",
"and",
"vomiting",
"were",
"more",
"common",
"with",
"CMF",
";",
"diarrhoea",
",",
"abdominal",
"pain",
",",
"dysgeusia",
",",
"neuropathy",
"and",
"liver",
"toxicity",
"were",
"more",
"frequent",
"with",
"docetaxel",
".",
"No",
"significant",
"interaction",
"was",
"found",
"between",
"the",
"occurrence",
"of",
"severe",
"toxicity",
"and",
"baseline",
"variables",
",",
"including",
"creatinine",
"clearance",
"and",
"geriatric",
"activity",
"scales",
".",
"In",
"conclusion",
",",
"weekly",
"docetaxel",
"appears",
"to",
"be",
"less",
"toxic",
"than",
"CMF",
"in",
"terms",
"of",
"hematological",
"toxicity",
"."
] | [
0,
17,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
7,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
27,
0,
31,
32,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
27,
0,
31,
32,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
27,
0,
31,
32,
0,
0,
25,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
21,
0,
21,
0,
21,
22,
0,
0,
0,
0,
0,
21,
0,
21,
0,
21,
0,
21,
0,
0,
0,
0,
0,
0,
21,
0,
21,
22,
0,
21,
0,
21,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
84 | [
"Association",
"of",
"Transforming",
"Growth",
"Factor",
"β",
"Polymorphism",
"C-",
"509",
"T",
"With",
"Radiation",
"-",
"Induced",
"Fibrosis",
"Among",
"Patients",
"With",
"Early",
"-",
"Stage",
"Breast",
"Cancer",
":",
"A",
"Secondary",
"Analysis",
"of",
"a",
"Randomized",
"Clinical",
"Trial",
".",
"Whether",
"genetic",
"factors",
"can",
"identify",
"patients",
"at",
"risk",
"for",
"radiation",
"-",
"induced",
"fibrosis",
"remains",
"unconfirmed",
".",
"To",
"assess",
"the",
"association",
"between",
"the",
"C-",
"509",
"T",
"variant",
"allele",
"in",
"the",
"promoter",
"region",
"of",
"TGFB",
"1",
"and",
"breast",
"fibrosis",
"3",
"years",
"after",
"radiotherapy",
".",
"This",
"is",
"an",
"a",
"priori",
"-",
"specified",
",",
"prospective",
",",
"cohort",
"study",
"nested",
"in",
"an",
"open",
"-",
"label",
",",
"randomized",
"clinical",
"trial",
",",
"which",
"was",
"conducted",
"in",
"community",
"-",
"based",
"and",
"academic",
"cancer",
"centers",
"to",
"compare",
"hypofractionated",
"whole",
"-",
"breast",
"irradiation",
"(",
"WBI",
")",
"(",
"42.56",
"Gy",
"in",
"16",
"fractions",
")",
"with",
"conventionally",
"fractionated",
"WBI",
"(",
"50",
"Gy",
"in",
"25",
"fractions",
")",
"after",
"breast",
"-",
"conserving",
"surgery",
".",
"In",
"total",
",",
"287",
"women",
"40",
"years",
"or",
"older",
"with",
"pathologically",
"confirmed",
"stage",
"0",
"to",
"IIA",
"breast",
"cancer",
"treated",
"with",
"breast",
"-",
"conserving",
"surgery",
"were",
"enrolled",
"from",
"February",
"2011",
"to",
"February",
"2014",
".",
"Patients",
"were",
"observed",
"for",
"a",
"minimum",
"of",
"3",
"years",
".",
"Outcomes",
"were",
"compared",
"using",
"the",
"1",
"-sided",
"Fisher",
"exact",
"test",
"and",
"multivariable",
"logistic",
"regression",
".",
"A",
"C",
"-",
"to",
"-",
"T",
"single",
"-",
"nucleotide",
"polymorphism",
"at",
"position",
"-",
"509",
"relative",
"to",
"the",
"first",
"major",
"transcription",
"start",
"site",
"(",
"C-",
"509",
"T",
")",
"of",
"the",
"TGFB",
"1",
"gene",
".",
"The",
"primary",
"outcome",
"was",
"grade",
"2",
"or",
"higher",
"breast",
"fibrosis",
"as",
"assessed",
"using",
"the",
"Late",
"Effects",
"Normal",
"Tissue",
"/",
"Subjective",
",",
"Objective",
",",
"Medical",
"Management",
",",
"Analytic",
"scale",
"(",
"range",
",",
"0",
"to",
"3",
")",
"three",
"years",
"after",
"radiotherapy",
".",
"Among",
"287",
"women",
"enrolled",
"in",
"the",
"trial",
",",
"TGFB",
"1",
"genotype",
"and",
"3",
"-year",
"radiotherapy",
"-",
"induced",
"toxicity",
"data",
"were",
"available",
"for",
"174",
"patients",
",",
"of",
"whom",
"89",
"patients",
"(",
"51",
"%",
")",
"with",
"a",
"mean",
"(",
"SD",
")",
"age",
"of",
"60",
"(",
"8",
")",
"years",
"had",
"at",
"least",
"1",
"copy",
"of",
"C-",
"509",
"T",
".",
"Grade",
"2",
"or",
"higher",
"breast",
"fibrosis",
"was",
"present",
"in",
"12",
"of",
"87",
"patients",
"with",
"C-",
"509",
"T",
"(",
"13.8",
"%",
")",
"compared",
"with",
"3",
"of",
"80",
"patients",
"without",
"the",
"allele",
"variant",
"(",
"3.8",
"%",
")",
"(",
"absolute",
"difference",
",",
"10.0",
"%",
";",
"95",
"%",
"CI",
",",
"1.7",
"%",
"-",
"18.4",
"%",
";",
"P",
"=",
".",
"02",
")",
".",
"The",
"results",
"of",
"multivariable",
"analyses",
"indicated",
"that",
"only",
"C-",
"509",
"T",
"(",
"odds",
"ratio",
",",
"4.47",
";",
"95",
"%",
"CI",
",",
"1.25",
"-",
"15.99",
";",
"P",
"=",
".",
"02",
")",
"and",
"postoperative",
"cosmetic",
"outcome",
"(",
"odds",
"ratio",
",",
"7.09",
";",
"95",
"%",
"CI",
",",
"2.41",
"-",
"20.90",
";",
"P",
"<",
".",
"001",
")",
"were",
"significantly",
"associated",
"with",
"breast",
"fibrosis",
"risk",
".",
"To",
"date",
",",
"this",
"study",
"seems",
"to",
"be",
"the",
"first",
"prospective",
"validation",
"of",
"a",
"genomic",
"marker",
"for",
"radiation",
"fibrosis",
".",
"The",
"C-",
"509",
"T",
"allele",
"in",
"TGFB",
"1",
"is",
"a",
"key",
"determinant",
"of",
"breast",
"fibrosis",
"risk",
".",
"Assessing",
"TGFB",
"1",
"genotype",
"may",
"facilitate",
"a",
"more",
"personalized",
"approach",
"to",
"locoregional",
"treatment",
"decisions",
"in",
"breast",
"cancer",
".",
"ClinicalTrials.gov",
"identifier",
":",
"NCT",
"01266642",
"."
] | [
0,
0,
17,
18,
18,
18,
18,
18,
18,
18,
0,
13,
14,
14,
14,
0,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
7,
8,
8,
8,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
85 | [
"Effect",
"of",
"everolimus",
"on",
"bone",
"marker",
"levels",
"and",
"progressive",
"disease",
"in",
"bone",
"in",
"BOLERO-",
"2",
".",
"Breast",
"Cancer",
"Trials",
"of",
"Oral",
"Everolimus",
"2",
"(",
"BOLERO-",
"2",
")",
",",
"a",
"phase",
"III",
"study",
"in",
"postmenopausal",
"women",
"with",
"estrogen",
"receptor",
"-",
"positive",
"breast",
"cancer",
"progressing",
"despite",
"nonsteroidal",
"aromatase",
"inhibitor",
"therapy",
",",
"showed",
"statistically",
"significant",
"benefits",
"with",
"adding",
"everolimus",
"to",
"exemestane",
".",
"Moreover",
",",
"in",
"preclinical",
"studies",
",",
"mammalian",
"target",
"of",
"rapamycin",
"inhibition",
"was",
"associated",
"with",
"decreased",
"osteoclast",
"survival",
"and",
"activity",
".",
"Exploratory",
"analyses",
"in",
"BOLERO-",
"2",
"evaluated",
"the",
"effect",
"of",
"everolimus",
"on",
"bone",
"marker",
"levels",
"and",
"progressive",
"disease",
"in",
"bone",
".",
"Patients",
"were",
"treated",
"with",
"exemestane",
"(",
"25",
"mg",
"/",
"day",
")",
"and",
"randomized",
"(",
"2",
":1",
")",
"to",
"everolimus",
"(",
"10",
"mg",
"/",
"day",
";",
"combination",
")",
"or",
"placebo",
"(",
"exemestane",
"only",
")",
".",
"Exploratory",
"endpoints",
"included",
"changes",
"in",
"bone",
"turnover",
"marker",
"levels",
"vs",
"baseline",
"and",
"progressive",
"disease",
"in",
"bone",
",",
"defined",
"as",
"unequivocal",
"progression",
"of",
"a",
"preexisting",
"bone",
"lesion",
"or",
"the",
"appearance",
"of",
"a",
"new",
"bone",
"lesion",
".",
"Baseline",
"disease",
"characteristics",
"were",
"well",
"balanced",
"between",
"arms",
"(",
"N",
"=",
"724",
")",
";",
"baseline",
"bisphosphonate",
"use",
"was",
"not",
"(",
"43.9",
"%",
"combination",
"vs",
"54.0",
"%",
"exemestane",
"only",
")",
".",
"At",
"a",
"median",
"of",
"18",
"months",
"of",
"follow",
"-",
"up",
",",
"median",
"progression",
"-",
"free",
"survival",
"(",
"primary",
"endpoint",
")",
"was",
"statistically",
"significantly",
"longer",
"with",
"the",
"combination",
"vs",
"exemestane",
"only",
"(",
"Cox",
"proportional",
"hazard",
"ratio",
"=",
"0.45",
",",
"95",
"%",
"confidence",
"interval",
"=",
"0.38",
"to",
"0.54",
";",
"log",
"-",
"rank",
",",
"1",
"-sided",
"P",
"<",
".",
"0001",
")",
".",
"Bone",
"marker",
"levels",
"at",
"6",
"and",
"12",
"weeks",
"increased",
"with",
"exemestane",
"only",
",",
"as",
"expected",
",",
"but",
"decreased",
"with",
"the",
"combination",
".",
"The",
"cumulative",
"incidence",
"rate",
"of",
"progressive",
"disease",
"in",
"bone",
"was",
"lower",
"in",
"the",
"combination",
"arm",
".",
"Bone",
"-",
"related",
"adverse",
"events",
"occurred",
"with",
"similar",
"frequency",
"in",
"both",
"arms",
"(",
"3.3",
"%",
"combination",
"vs",
"4.2",
"%",
"exemestane",
"only",
")",
".",
"These",
"exploratory",
"analyses",
"suggest",
"that",
"everolimus",
"has",
"beneficial",
"effects",
"on",
"bone",
"turnover",
"and",
"progressive",
"disease",
"in",
"bone",
"in",
"patients",
"receiving",
"exemestane",
"for",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
"progressing",
"during",
"/",
"after",
"nonsteroidal",
"aromatase",
"inhibitor",
"therapy",
"."
] | [
0,
0,
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
86 | [
"Use",
"of",
"axillary",
"deodorant",
"and",
"effect",
"on",
"acute",
"skin",
"toxicity",
"during",
"radiotherapy",
"for",
"breast",
"cancer",
":",
"a",
"prospective",
"randomized",
"noninferiority",
"trial",
".",
"To",
"prospectively",
"determine",
"the",
"effect",
"of",
"deodorant",
"use",
"on",
"acute",
"skin",
"toxicity",
"and",
"quality",
"of",
"life",
"during",
"breast",
"radiotherapy",
"(",
"RT",
")",
".",
"Before",
"breast",
"RT",
",",
"84",
"patients",
"were",
"randomly",
"assigned",
"to",
"the",
"deodorant",
"group",
"(",
"n",
"=",
"40",
")",
"or",
"the",
"no",
"-",
"deodorant",
"group",
"(",
"n",
"=",
"44",
")",
".",
"The",
"patients",
"were",
"stratified",
"by",
"axillary",
"RT",
"and",
"previous",
"chemotherapy",
".",
"Toxicity",
"evaluations",
"were",
"always",
"performed",
"by",
"the",
"principal",
"investigator",
",",
"who",
"was",
"unaware",
"of",
"the",
"group",
"assignment",
",",
"at",
"the",
"end",
"of",
"RT",
"and",
"2",
"weeks",
"after",
"completion",
"using",
"the",
"Radiation",
"Therapy",
"Oncology",
"Group",
"acute",
"skin",
"toxicity",
"criteria",
".",
"Symptoms",
"of",
"acute",
"skin",
"toxicity",
"(",
"i.",
"e.",
",",
"discomfort",
",",
"pain",
",",
"pruritus",
",",
"sweating",
")",
"and",
"quality",
"of",
"life",
"were",
"self",
"-",
"evaluated",
".",
"For",
"each",
"criterion",
",",
"the",
"point",
"estimate",
"of",
"rate",
"difference",
"with",
"the",
"95",
"%",
"one",
"-",
"sided",
"upper",
"confidence",
"limit",
"was",
"computed",
".",
"To",
"claim",
"noninferiority",
"owing",
"to",
"deodorant",
"use",
",",
"the",
"95",
"%",
"one",
"-",
"sided",
"upper",
"confidence",
"limit",
"had",
"to",
"be",
"lower",
"than",
"the",
"noninferiority",
"margin",
",",
"fixed",
"to",
"12.8",
"%",
".",
"In",
"the",
"deodorant",
"vs.",
"no",
"-",
"deodorant",
"groups",
",",
"Grade",
"2",
"axillary",
"radiodermatitis",
"occurred",
"in",
"23",
"%",
"vs.",
"30",
"%",
",",
"respectively",
",",
"satisfying",
"the",
"statistical",
"criteria",
"for",
"noninferiority",
"(",
"p",
"=",
".",
"019",
")",
".",
"Grade",
"2",
"breast",
"radiodermatitis",
"occurred",
"in",
"30",
"%",
"vs.",
"34",
"%",
"of",
"the",
"deodorant",
"vs.",
"no",
"-",
"deodorant",
"groups",
",",
"respectively",
",",
"also",
"satisfying",
"the",
"statistical",
"criteria",
"for",
"noninferiority",
"(",
"p",
"=",
".",
"049",
")",
".",
"Similar",
"results",
"were",
"observed",
"for",
"the",
"self",
"-",
"reported",
"evaluations",
".",
"The",
"deodorant",
"group",
"reported",
"less",
"sweating",
"(",
"18",
"%",
"vs.",
"39",
"%",
",",
"p",
"=",
".",
"032",
")",
".",
"No",
"Grade",
"3",
"or",
"4",
"radiodermatitis",
"was",
"observed",
".",
"According",
"to",
"our",
"noninferiority",
"margin",
"definition",
",",
"the",
"occurrence",
"of",
"skin",
"toxicity",
"and",
"its",
"related",
"symptoms",
"were",
"statistically",
"equivalent",
"in",
"both",
"groups",
".",
"No",
"evidence",
"was",
"found",
"to",
"prohibit",
"deodorant",
"use",
"(",
"notwithstanding",
"the",
"use",
"of",
"an",
"antiperspirant",
"with",
"aluminum",
")",
"during",
"RT",
"for",
"breast",
"cancer",
"."
] | [
0,
0,
17,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
19,
20,
20,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
87 | [
"Topical",
"silymarin",
"administration",
"for",
"prevention",
"of",
"acute",
"radiodermatitis",
"in",
"breast",
"cancer",
"patients",
":",
"A",
"randomized",
",",
"double",
"-",
"blind",
",",
"placebo",
"-",
"controlled",
"clinical",
"trial",
".",
"Radiation",
"-",
"induced",
"dermatitis",
"is",
"one",
"of",
"the",
"most",
"common",
"side",
"effects",
"of",
"radiotherapy",
".",
"Silymarin",
",",
"a",
"flavonoid",
"extracted",
"from",
"the",
"Silybum",
"marianum",
",",
"exhibits",
"antioxidant",
"and",
"anti",
"-",
"inflammatory",
"activities",
".",
"The",
"purpose",
"of",
"this",
"study",
"was",
"to",
"investigate",
"the",
"efficacy",
"of",
"silymarin",
"gel",
"in",
"prevention",
"of",
"radiodermatitis",
"in",
"patients",
"with",
"breast",
"cancer",
".",
"During",
"this",
"randomized",
",",
"double",
"-",
"blinded",
",",
"placebo",
"-",
"controlled",
"clinical",
"trial",
",",
"the",
"preventive",
"effect",
"of",
"silymarin",
"1",
"%",
"gel",
"was",
"assessed",
"in",
"comparison",
"with",
"placebo",
",",
"on",
"radiodermatitis",
"occurrence",
".",
"Forty",
"patients",
"randomly",
"received",
"silymarin",
"gel",
"or",
"placebo",
"formulation",
"on",
"chest",
"wall",
"skin",
"following",
"modified",
"radical",
"mastectomy",
",",
"once",
"daily",
"starting",
"at",
"the",
"first",
"day",
"of",
"radiotherapy",
"for",
"5",
"weeks",
".",
"Radiodermatitis",
"severity",
"was",
"assessed",
"weekly",
"based",
"on",
"Radiation",
"Therapy",
"Oncology",
"Group",
"(",
"RTOG",
")",
"and",
"National",
"Cancer",
"Institute",
"Common",
"Terminology",
"for",
"Adverse",
"Events",
"(",
"NCI",
"-",
"CTCAE",
")",
"criteria",
"radiodermatits",
"grading",
"scale",
"for",
"5",
"weeks",
".",
"The",
"median",
"NCI",
"-",
"CTCAE",
"and",
"RTOG",
"scores",
"were",
"significantly",
"lower",
"in",
"silymarin",
"group",
"at",
"the",
"end",
"of",
"the",
"third",
"to",
"fifth",
"weeks",
"(",
"p",
"value",
"<",
"0.05",
")",
".",
"The",
"scores",
"increased",
"significantly",
"in",
"both",
"placebo",
"and",
"silymarin",
"groups",
"during",
"radiotherapy",
",",
"but",
"there",
"was",
"a",
"delay",
"in",
"radiodermatitis",
"development",
"and",
"progression",
"in",
"silymarin",
"group",
".",
"Prophylactic",
"administration",
"of",
"silymarin",
"gel",
"could",
"significantly",
"reduce",
"the",
"severity",
"of",
"radiodermatitis",
"and",
"delay",
"its",
"occurrence",
"after",
"5",
"weeks",
"of",
"application",
"."
] | [
17,
18,
0,
0,
0,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
88 | [
"Longitudinal",
"social",
"cognitive",
"influences",
"on",
"physical",
"activity",
"and",
"sedentary",
"time",
"in",
"Hispanic",
"breast",
"cancer",
"survivors",
".",
"This",
"study",
"evaluated",
"the",
"effect",
"of",
"two",
"home",
"-",
"based",
"exercise",
"interventions",
"(",
"one",
"culturally",
"adapted",
"and",
"one",
"standard",
")",
"on",
"changes",
"in",
"social",
"cognitive",
"theory",
"(",
"SCT",
")",
"variables",
",",
"physical",
"activity",
"(",
"PA",
")",
",",
"and",
"sedentary",
"time",
"(",
"ST",
")",
",",
"and",
"determined",
"the",
"association",
"between",
"changes",
"in",
"SCT",
"variables",
"and",
"changes",
"in",
"PA",
"and",
"ST",
"in",
"Hispanic",
"breast",
"cancer",
"survivors",
".",
"Project",
"VIVA",
"!",
"was",
"a",
"16",
"-week",
"randomized",
"controlled",
"pilot",
"study",
"to",
"test",
"the",
"effectiveness",
"and",
"feasibility",
"of",
"a",
"culturally",
"adapted",
"exercise",
"intervention",
"for",
"Mexican",
"American",
"and",
"Puerto",
"Rican",
"breast",
"cancer",
"survivors",
"in",
"Houston",
",",
"Texas",
"and",
"San",
"Juan",
",",
"Puerto",
"Rico",
",",
"respectively",
".",
"Women",
"(",
"N",
"=",
"89",
")",
"completed",
"questionnaires",
"on",
"SCT",
"variables",
",",
"PA",
",",
"and",
"ST",
"and",
"were",
"then",
"randomized",
"to",
"a",
"16",
"-week",
"culturally",
"adapted",
"exercise",
"program",
",",
"a",
"non",
"-",
"culturally",
"adapted",
"standard",
"exercise",
"intervention",
"or",
"a",
"wait",
"-",
"list",
"control",
"group",
".",
"Multiple",
"regression",
"models",
"were",
"used",
"to",
"determine",
"associations",
"between",
"changes",
"in",
"SCT",
"variables",
"and",
"changes",
"in",
"PA",
"and",
"ST",
".",
"Participants",
"were",
"in",
"their",
"late",
"50",
"s",
"(",
"58.5",
"±",
"9.2",
"years",
")",
"and",
"obese",
"(",
"31.0",
"±",
"6.5",
"kg",
"/",
"m",
"2",
")",
".",
"Women",
"reported",
"doing",
"roughly",
"34.5",
"min",
"/",
"day",
"of",
"PA",
"and",
"spending",
"over",
"11",
"h",
"/",
"day",
"in",
"sedentary",
"activities",
".",
"Across",
"groups",
",",
"women",
"reported",
"significant",
"increases",
"in",
"exercise",
"self",
"-",
"efficacy",
"and",
"moderate",
"-",
"intensity",
",",
"vigorous",
"-",
"intensity",
",",
"and",
"total",
"PA",
"from",
"baseline",
"to",
"follow",
"-",
"up",
"(",
"p",
"<",
"0.05",
")",
".",
"Increased",
"social",
"support",
"from",
"family",
"was",
"associated",
"with",
"increases",
"in",
"vigorous",
"-",
"intensity",
"PA",
".",
"Increases",
"in",
"social",
"modeling",
"were",
"associated",
"with",
"increases",
"in",
"moderate",
"-",
"intensity",
"and",
"total",
"PA",
"and",
"with",
"decreases",
"in",
"ST",
"from",
"baseline",
"to",
"follow",
"-",
"up",
"(",
"p",
"<",
"0.05",
")",
".",
"Hispanic",
"cancer",
"survivors",
"benefit",
"from",
"PA",
"interventions",
"that",
"focus",
"on",
"increasing",
"social",
"support",
"from",
"family",
"and",
"friends",
"and",
"social",
"modeling",
".",
"Copyright",
"©",
"2015",
"John",
"Wiley",
"&",
"Sons",
",",
"Ltd."
] | [
0,
0,
0,
0,
0,
17,
18,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
0,
11,
12,
0,
0,
0,
0,
15,
0,
15,
0,
15,
16,
0,
15,
16,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
21,
22,
22,
0,
21,
22,
22,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
22,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
89 | [
"Maintaining",
"normal",
"hemoglobin",
"levels",
"with",
"epoetin",
"alfa",
"in",
"mainly",
"nonanemic",
"patients",
"with",
"metastatic",
"breast",
"cancer",
"receiving",
"first",
"-",
"line",
"chemotherapy",
":",
"a",
"survival",
"study",
".",
"To",
"evaluate",
"the",
"effect",
"on",
"survival",
"and",
"quality",
"of",
"life",
"of",
"maintaining",
"hemoglobin",
"(",
"Hb",
")",
"in",
"the",
"range",
"of",
"12",
"to",
"14",
"g",
"/",
"dL",
"with",
"epoetin",
"alfa",
"versus",
"placebo",
"in",
"women",
"with",
"metastatic",
"breast",
"cancer",
"(",
"MBC",
")",
"receiving",
"first",
"-",
"line",
"chemotherapy",
".",
"Eligible",
"patients",
"were",
"randomly",
"assigned",
"to",
"receive",
"epoetin",
"alfa",
"40",
",",
"000",
"U",
"once",
"weekly",
"or",
"placebo",
"for",
"12",
"months",
".",
"Study",
"drug",
"was",
"initiated",
"if",
"baseline",
"Hb",
"was",
"<",
"or",
"=",
"13",
"g",
"/",
"dL",
"or",
"when",
"Hb",
"decreased",
"to",
"<",
"or",
"=",
"13",
"g",
"/",
"dL",
"during",
"the",
"study",
".",
"The",
"primary",
"end",
"point",
"was",
"12",
"-month",
"overall",
"survival",
"(",
"OS",
")",
".",
"The",
"study",
"drug",
"administration",
"was",
"stopped",
"early",
"in",
"accordance",
"with",
"a",
"recommendation",
"from",
"the",
"Independent",
"Data",
"Monitoring",
"Committee",
"because",
"of",
"higher",
"mortality",
"in",
"the",
"group",
"treated",
"with",
"epoetin",
"alfa",
".",
"Enrollment",
"had",
"been",
"completed",
",",
"with",
"939",
"patients",
"enrolled",
"(",
"epoetin",
"alfa",
",",
"n",
"=",
"469",
";",
"placebo",
",",
"n",
"=",
"470",
")",
".",
"Most",
"patients",
"had",
"Hb",
"more",
"than",
"12",
"g",
"/",
"dL",
"at",
"baseline",
"(",
"median",
"Hb",
",",
"12.8",
"g",
"/",
"dL",
")",
"or",
"during",
"the",
"study",
".",
"From",
"the",
"final",
"analysis",
",",
"12",
"-month",
"OS",
"was",
"70",
"%",
"for",
"epoetin",
"alfa",
"recipients",
"and",
"76",
"%",
"for",
"placebo",
"recipients",
"(",
"P",
"=",
".",
"01",
")",
".",
"Optimal",
"tumor",
"response",
"and",
"time",
"to",
"disease",
"progression",
"were",
"similar",
"between",
"groups",
".",
"The",
"reason",
"for",
"the",
"difference",
"in",
"mortality",
"between",
"groups",
"could",
"not",
"be",
"determined",
"from",
"additional",
"subsequent",
"analyses",
"involving",
"both",
"study",
"data",
"and",
"chart",
"review",
".",
"In",
"this",
"trial",
",",
"the",
"use",
"of",
"epoetin",
"alfa",
"to",
"maintain",
"high",
"Hb",
"targets",
"in",
"women",
"with",
"MBC",
",",
"most",
"of",
"whom",
"did",
"not",
"have",
"anemia",
"at",
"the",
"start",
"of",
"treatment",
",",
"was",
"associated",
"with",
"decreased",
"survival",
".",
"Additional",
"research",
"is",
"required",
"to",
"clarify",
"the",
"potential",
"impact",
"of",
"erythropoietic",
"agents",
"on",
"survival",
"when",
"the",
"Hb",
"target",
"range",
"is",
"10",
"to",
"12",
"g",
"/",
"dL",
"."
] | [
0,
0,
0,
0,
0,
17,
18,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
90 | [
"[",
"Comparison",
"between",
"intratumoral",
"and",
"peritumoral",
"injection",
"of",
"radiotracer",
"for",
"locating",
"and",
"biopsying",
"the",
"sentinel",
"lymph",
"node",
"in",
"nonpalpable",
"breast",
"cancer",
"]",
".",
"To",
"determine",
"whether",
"there",
"are",
"differences",
"in",
"the",
"technical",
"efficacy",
"in",
"detecting",
"and",
"biopsying",
"the",
"sentinel",
"node",
"after",
"intratumoral",
"or",
"peritumoral",
"administration",
"of",
"the",
"radiotracer",
"in",
"patients",
"with",
"nonpalpable",
"early",
"-",
"stage",
"breast",
"cancer",
".",
"This",
"prospective",
",",
"randomized",
"study",
"included",
"80",
"patients",
"with",
"nonpalpable",
"breast",
"cancer",
"without",
"axillary",
"adenopathies",
"who",
"were",
"scheduled",
"for",
"primary",
"surgical",
"treatment",
".",
"Patients",
"were",
"randomized",
"to",
"one",
"of",
"two",
"groups",
":",
"the",
"INTRA",
"group",
"(",
"intratumoral",
"radiotracer",
"administration",
",",
"n=",
"35",
")",
"or",
"the",
"PERI",
"group",
"(",
"peritumoral",
"radiotracer",
"administration",
",",
"n=",
"45",
")",
".",
"Patients",
"with",
"suspicious",
"axillary",
"lymph",
"nodes",
"at",
"clinical",
"or",
"ultrasonographic",
"examination",
"that",
"had",
"positive",
"results",
"after",
"fine",
"-",
"needle",
"aspiration",
"cytology",
"were",
"excluded",
".",
"The",
"rates",
"of",
"sentinel",
"node",
"detection",
"were",
"97.1",
"%",
"(",
"34",
"/",
"35",
")",
"for",
"intratumoral",
"injection",
"and",
"84.4",
"%",
"(",
"38",
"/",
"45",
")",
"for",
"peritumoral",
"injection",
".",
"Radiotracer",
"migration",
"failure",
"occurred",
"in",
"8",
"cases",
"(",
"one",
"in",
"the",
"INTRA",
"group",
"and",
"7",
"in",
"the",
"PERI",
"group",
")",
".",
"The",
"sentinel",
"node",
"was",
"detected",
"in",
"an",
"extra",
"-",
"axillary",
"location",
"in",
"21.9",
"%",
"of",
"cases",
"(",
"11",
"/",
"59",
"in",
"the",
"INTRA",
"group",
"and",
"16",
"/",
"64",
"in",
"the",
"PERI",
"group",
")",
".",
"Our",
"study",
"found",
"no",
"statistically",
"significant",
"differences",
"in",
"the",
"detection",
"rates",
"of",
"axillary",
"or",
"extra",
"-",
"axillary",
"sentinel",
"lymph",
"nodes",
"between",
"the",
"two",
"groups",
";",
"however",
",",
"we",
"observed",
"greater",
"technical",
"efficacy",
"with",
"intratumoral",
"radiotracer",
"administration",
"."
] | [
0,
0,
0,
17,
0,
19,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
29,
30,
0,
25,
0,
3,
0,
0,
0,
0,
0,
31,
32,
0,
27,
0,
5,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
25,
0,
0,
0,
0,
0,
27,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
25,
0,
3,
0,
0,
0,
0,
0,
27,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
91 | [
"Differences",
"between",
"palpable",
"and",
"nonpalpable",
"tumors",
"in",
"early",
"-",
"stage",
",",
"hormone",
"receptor",
"-",
"positive",
"breast",
"cancer",
".",
"We",
"compared",
"characteristics",
"and",
"outcomes",
"of",
"palpable",
"versus",
"nonpalpable",
",",
"hormone",
"-",
"sensitive",
",",
"early",
"-",
"stage",
"breast",
"cancers",
".",
"Patients",
"from",
"the",
"North",
"American",
"Fareston",
"vs.",
"Tamoxifen",
"Adjuvant",
"(",
"NAFTA",
")",
"trial",
"were",
"divided",
"into",
"palpable",
"(",
"n",
"=",
"513",
")",
"and",
"nonpalpable",
"(",
"n",
"=",
"1063",
")",
"tumor",
"groups",
".",
"Differences",
"in",
"pathological",
"features",
",",
"loco",
"-",
"regional",
"therapy",
",",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
"and",
"overall",
"survival",
"(",
"OS",
")",
"were",
"analyzed",
".",
"Patients",
"with",
"palpable",
"tumors",
"were",
"older",
",",
"had",
"larger",
"tumors",
",",
"and",
"higher",
"rates",
"of",
"lymph",
"-",
"node",
"involvement",
".",
"The",
"tumors",
"were",
"more",
"likely",
"to",
"be",
"poorly",
"differentiated",
",",
"of",
"high",
"nuclear",
"grade",
",",
"and",
"display",
"lymphovascular",
"invasion",
".",
"After",
"mean",
"followup",
"of",
"59",
"months",
",",
"DFS",
"and",
"OS",
"were",
"significantly",
"lower",
"for",
"palpable",
"than",
"nonpalpable",
"tumors",
"(",
"DFS",
"93.5",
"%",
"vs.",
"98.4",
"%",
",",
"p",
"<",
"0.001",
",",
"OS",
"88.5",
"%",
"vs.",
"95.6",
"%",
",",
"p",
"<",
"0.001",
")",
".",
"Controlling",
"for",
"age",
",",
"size",
"and",
"nodal",
"status",
",",
"palpability",
"was",
"an",
"independent",
"factor",
"for",
"DFS",
"(",
"OR",
"=",
"2.56",
";",
"95",
"%",
"CI",
",",
"1.37",
"-",
"4.79",
",",
"p",
"=",
"0.003",
")",
"and",
"OS",
"(",
"OR",
"=",
"2.12",
";",
"95",
"%",
"CI",
",",
"1.38",
"-",
"3.28",
",",
"p",
"<",
"0.001",
")",
".",
"In",
"a",
"group",
"of",
"hormone",
"-",
"sensitive",
",",
"mostly",
"postmenopausal",
"early",
"-",
"stage",
"breast",
"cancer",
"patients",
",",
"palpable",
"tumors",
"were",
"more",
"likely",
"to",
"have",
"more",
"aggressive",
"features",
"and",
"metastatic",
"potential",
",",
"which",
"translated",
"in",
"to",
"a",
"higher",
"incidence",
"of",
"breast",
"cancer",
"-",
"related",
"events",
"and",
"worse",
"overall",
"survival",
"."
] | [
0,
0,
17,
0,
19,
20,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
16,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
21,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
92 | [
"Selecting",
"the",
"optimal",
"position",
"of",
"CDK",
"4",
"/",
"6",
"inhibitors",
"in",
"hormone",
"receptor",
"-",
"positive",
"advanced",
"breast",
"cancer",
"-",
"the",
"SONIA",
"study",
":",
"study",
"protocol",
"for",
"a",
"randomized",
"controlled",
"trial",
".",
"Combining",
"cyclin",
"-",
"dependent",
"kinases",
"4",
"and",
"6",
"(",
"CDK",
"4",
"/",
"6",
")",
"inhibitors",
"with",
"endocrine",
"therapy",
"is",
"an",
"effective",
"strategy",
"to",
"improve",
"progression",
"-",
"free",
"survival",
"in",
"hormone",
"receptor",
"-",
"positive",
"(",
"HR+",
")",
",",
"human",
"epidermal",
"growth",
"factor",
"receptor",
"2",
"(",
"HER",
"2",
")",
"-negative",
"advanced",
"breast",
"cancer",
".",
"There",
"is",
"a",
"lack",
"of",
"comparative",
"data",
"to",
"help",
"clinicians",
"decide",
"if",
"CDK",
"4",
"/",
"6",
"inhibitors",
"can",
"best",
"be",
"added",
"to",
"first-",
"or",
"second",
"-",
"line",
"endocrine",
"therapy",
".",
"Improvement",
"in",
"median",
"progression",
"-",
"free",
"survival",
"in",
"first",
"-",
"line",
"studies",
"is",
"larger",
"than",
"in",
"second",
"-",
"line",
"studies",
",",
"but",
"CDK",
"4",
"/",
"6",
"inhibitors",
"have",
"not",
"consistently",
"shown",
"to",
"improve",
"overall",
"survival",
"or",
"quality",
"of",
"life",
".",
"They",
"do",
"come",
"with",
"added",
"toxicity",
"and",
"costs",
",",
"and",
"many",
"patients",
"have",
"lasting",
"disease",
"remission",
"on",
"endocrine",
"therapy",
"alone",
".",
"No",
"subgroup",
"has",
"been",
"identified",
"to",
"select",
"patients",
"who",
"are",
"most",
"likely",
"to",
"benefit",
"from",
"the",
"addition",
"of",
"CDK",
"4",
"/",
"6",
"inhibition",
"in",
"any",
"line",
"of",
"treatment",
".",
"Altogether",
",",
"these",
"factors",
"make",
"that",
"the",
"optimal",
"strategy",
"for",
"using",
"CDK",
"4",
"/",
"6",
"inhibitors",
"in",
"clinical",
"practice",
"is",
"unknown",
".",
"The",
"SONIA",
"study",
"is",
"an",
"investigator",
"-",
"initiated",
",",
"multicenter",
",",
"randomized",
"phase",
"III",
"study",
"in",
"patients",
"with",
"HR+",
"/",
"HER",
"2",
"-",
"negative",
"advanced",
"breast",
"cancer",
".",
"Patients",
"are",
"randomly",
"assigned",
"to",
"receive",
"either",
"strategy",
"A",
"(",
"first",
"-",
"line",
"treatment",
"with",
"a",
"non",
"-",
"steroidal",
"aromatase",
"inhibitor",
"combined",
"with",
"CDK",
"4",
"/",
"6",
"inhibition",
",",
"followed",
"on",
"progression",
"by",
"fulvestrant",
")",
"or",
"strategy",
"B",
"(",
"first",
"-",
"line",
"treatment",
"with",
"a",
"non",
"-",
"steroidal",
"aromatase",
"inhibitor",
",",
"followed",
"on",
"progression",
"by",
"fulvestrant",
"combined",
"with",
"CDK",
"4",
"/",
"6",
"inhibition",
")",
".",
"The",
"primary",
"objective",
"is",
"to",
"test",
"whether",
"strategy",
"A",
"is",
"more",
"effective",
"than",
"strategy",
"B",
".",
"The",
"primary",
"endpoint",
"is",
"time",
"from",
"randomization",
"to",
"second",
"objective",
"progression",
"(",
"PFS",
"2",
")",
".",
"Secondary",
"endpoints",
"include",
"overall",
"survival",
",",
"safety",
",",
"quality",
"of",
"life",
",",
"and",
"cost",
"-",
"effectiveness",
".",
"Five",
"-",
"hundred",
"seventy",
"-",
"four",
"events",
"yield",
"89",
"%",
"power",
"to",
"show",
"that",
"strategy",
"A",
"has",
"statistically",
"significant",
",",
"clinically",
"meaningful",
"superior",
"PFS",
"2",
"(",
"according",
"to",
"ESMO",
"-",
"MCBS",
")",
"in",
"a",
"log",
"-",
"rank",
"test",
"at",
"the",
"two",
"-",
"sided",
"95",
"%",
"confidence",
"level",
".",
"Given",
"an",
"accrual",
"period",
"of",
"42",
"months",
"and",
"an",
"additional",
"18",
"months",
"follow",
"-",
"up",
",",
"inclusion",
"of",
"1050",
"evaluable",
"patients",
"is",
"required",
".",
"This",
"study",
"design",
"represents",
"daily",
"clinical",
"practice",
",",
"and",
"the",
"results",
"will",
"aid",
"clinicians",
"in",
"deciding",
"when",
"adding",
"CDK",
"4",
"/",
"6",
"inhibitors",
"to",
"endocrine",
"therapy",
"will",
"benefit",
"their",
"patients",
"most",
".",
"Additional",
"biomarker",
"analyses",
"may",
"help",
"to",
"optimize",
"patient",
"selection",
".",
"http:",
"/",
"/",
"clinicaltrials",
".",
"gov",
":",
"NCT",
"03425838",
"(",
"8",
"February",
"2018",
")",
".",
"EudraCT",
"-",
"number",
":",
"2017",
"-",
"002334",
"-",
"23",
"(",
"29",
"September",
"2017",
")",
"."
] | [
0,
0,
0,
0,
0,
17,
18,
18,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
23,
24,
0,
23,
0,
23,
24,
24,
0,
0,
23,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
93 | [
"Rivaroxaban",
"compared",
"to",
"no",
"treatment",
"in",
"ER",
"-",
"negative",
"stage",
"I",
"-",
"III",
"early",
"breast",
"cancer",
"patients",
"(",
"the",
"TIP",
"Trial",
")",
":",
"study",
"protocol",
"for",
"a",
"phase",
"II",
"preoperative",
"window",
"-",
"of",
"-",
"opportunity",
"study",
"design",
"randomised",
"controlled",
"trial",
".",
"Breast",
"cancer",
"patients",
"are",
"at",
"a",
"four",
"-",
"fold",
"increased",
"risk",
"of",
"developing",
"a",
"venous",
"thromboembolism",
"(",
"VTE",
")",
",",
"a",
"major",
"cause",
"of",
"death",
"in",
"this",
"group",
".",
"Conversely",
",",
"coagulation",
"factors",
"promote",
"tumour",
"growth",
"and",
"metastasis",
".",
"This",
"has",
"been",
"evidenced",
"in",
"preclinical",
"models",
",",
"with",
"an",
"inhibitory",
"effect",
"of",
"anticoagulants",
"on",
"cancer",
"growth",
"through",
"proliferative",
",",
"angiogenic",
",",
"apoptotic",
",",
"cancer",
"stem",
"cell",
"and",
"metastatic",
"processes",
".",
"The",
"extrinsic",
"clotting",
"pathway",
"is",
"also",
"more",
"upregulated",
"in",
"patients",
"in",
"the",
"relatively",
"poorer",
"prognosis",
"oestrogen",
"receptor",
"(",
"ER",
")",
"-negative",
"breast",
"cancer",
"subgroup",
",",
"with",
"increased",
"tumour",
"stromal",
"expression",
"of",
"the",
"coagulation",
"factors",
"Tissue",
"Factor",
"and",
"thrombin",
".",
"Rivaroxaban",
"(",
"Xarelto",
"®",
",",
"Bayer",
"AG",
",",
"Leverkusen",
",",
"Germany",
")",
"is",
"a",
"direct",
"oral",
"anticoagulant",
"(",
"DOAC",
")",
".",
"It",
"is",
"a",
"Factor",
"Xa",
"inhibitor",
"that",
"is",
"routinely",
"prescribed",
"for",
"the",
"prevention",
"of",
"stroke",
"in",
"non",
"-",
"valvular",
"atrial",
"fibrillation",
"and",
"for",
"both",
"VTE",
"prophylaxis",
"and",
"treatment",
".",
"This",
"trial",
"will",
"assess",
"the",
"anti",
"-",
"proliferative",
"and",
"other",
"anti",
"-",
"cancer",
"progression",
"mechanisms",
"of",
"Rivaroxaban",
"in",
"ER",
"-",
"negative",
"early",
"breast",
"cancer",
"patients",
".",
"This",
"UK",
"-",
"based",
"preoperative",
"window",
"-",
"of",
"-",
"opportunity",
"phase",
"II",
"randomised",
"control",
"trial",
"will",
"randomise",
"88",
"treatment",
"-",
"naïve",
"early",
"breast",
"cancer",
"patients",
"to",
"receive",
"20",
"mg",
"OD",
"Rivaroxaban",
"treatment",
"for",
"11",
"to",
"17",
"days",
"or",
"no",
"treatment",
".",
"Treatment",
"will",
"be",
"stopped",
"24",
"h",
"(",
"range",
"18",
"-",
"36",
"h",
")",
"prior",
"to",
"surgery",
"or",
"repeat",
"core",
"biopsy",
".",
"All",
"patients",
"will",
"be",
"followed",
"up",
"for",
"2",
"weeks",
"following",
"surgery",
"or",
"repeat",
"core",
"biopsy",
".",
"The",
"primary",
"endpoint",
"is",
"change",
"in",
"tumour",
"Ki",
"67",
".",
"Secondary",
"outcome",
"measures",
"include",
"tumour",
"markers",
"of",
"apoptosis",
"and",
"angiogenesis",
",",
"extrinsic",
"clotting",
"pathway",
"activation",
"and",
"systemic",
"markers",
"of",
"metastasis",
",",
"tumour",
"load",
"and",
"coagulation",
".",
"Laboratory",
"evidence",
"supports",
"an",
"anti",
"-",
"cancer",
"role",
"for",
"anticoagulants",
";",
"however",
",",
"this",
"has",
"failed",
"to",
"translate",
"into",
"survival",
"benefit",
"when",
"trialled",
"in",
"patients",
"with",
"metastatic",
"disease",
"or",
"poor",
"prognosis",
"cancers",
",",
"such",
"as",
"lung",
"cancer",
".",
"Subgroup",
"analysis",
"supported",
"a",
"potential",
"survival",
"benefit",
"in",
"better",
"prognosis",
"advanced",
"disease",
"patients",
".",
"This",
"is",
"the",
"first",
"study",
"to",
"investigate",
"the",
"anti",
"-",
"cancer",
"effects",
"of",
"anticoagulants",
"in",
"early",
"breast",
"cancer",
".",
"UK",
"National",
"Research",
"Ethics",
"Service",
"(",
"NRES",
")",
"approval",
"15",
"/NW",
"/",
"0406",
",",
"MHRA",
"Clinical",
"Trials",
"Authorisation",
"48380",
"/",
"0003",
"/",
"001",
"-",
"0001",
".",
"The",
"sponsor",
"is",
"Manchester",
"University",
"NHS",
"Foundation",
"Trust",
",",
"and",
"the",
"trial",
"is",
"co",
"-",
"ordinated",
"by",
"Cancer",
"Research",
"UK",
"Liverpool",
"Cancer",
"Trials",
"Unit",
"(",
"LCTU",
")",
".",
"EudraCT",
"2014",
"-",
"004909",
"-",
"33",
",",
"registered",
"27",
"July",
"2015",
".",
"ISRCTN",
"14785273",
"."
] | [
17,
0,
0,
19,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
94 | [
"An",
"open",
"-",
"label",
",",
"randomized",
",",
"multicenter",
"dose",
"-",
"finding",
"study",
"of",
"once",
"-",
"per",
"-",
"cycle",
"pegfilgrastim",
"versus",
"daily",
"filgrastim",
"in",
"Chinese",
"breast",
"cancer",
"patients",
"receiving",
"TAC",
"chemotherapy",
".",
"A",
"chemotherapy",
"regimen",
"of",
"docetaxel",
",",
"doxorubicin",
"and",
"cyclophosphamide",
"(",
"TAC",
")",
"has",
"been",
"accepted",
"as",
"a",
"standard",
"care",
"because",
"of",
"their",
"superior",
"clinical",
"benefit",
"in",
"early",
"-",
"stage",
"breast",
"cancer",
"patients",
",",
"but",
"with",
"a",
"higher",
"risk",
"of",
"neutropenia",
".",
"Pegfilgrastim",
"is",
"a",
"once",
"-",
"per",
"-",
"cycle",
"therapy",
"for",
"prophylactic",
"neutrophil",
"support",
"and",
"neutropenia",
"prevention",
".",
"There",
"was",
"still",
"a",
"lack",
"of",
"direct",
"evidences",
"for",
"finding",
"an",
"optimal",
"fixed",
"dose",
"of",
"pegfilgrastim",
"in",
"Chinese",
"breast",
"cancer",
"patients",
"receiving",
"TAC",
"regimen",
".",
"An",
"open",
"-",
"label",
",",
"randomized",
",",
"phase",
"II",
"study",
"was",
"designed",
"to",
"compare",
"the",
"effects",
"of",
"pegfilgrastim",
"with",
"filgrastim",
".",
"Eighteen",
"centers",
"in",
"China",
"enrolled",
"171",
"eligible",
"female",
"breast",
"cancer",
"patients",
"with",
"cycles",
"of",
"TAC",
"chemotherapy",
"treatment",
",",
"randomized",
"into",
"four",
"arms",
",",
"received",
"a",
"single",
"subcutaneous",
"injection",
"of",
"pegfilgrastim",
"(",
"60",
",",
"100",
"or",
"120",
"µg",
"/",
"kg",
")",
"per",
"chemotherapy",
"cycle",
"or",
"daily",
"subcutaneous",
"injections",
"of",
"filgrastim",
"5",
"µg",
"/",
"kg",
"24",
"h",
"after",
"chemotherapy",
".",
"Efficacy",
"and",
"safety",
"were",
"analyzed",
".",
"In",
"ITT",
"population",
",",
"the",
"mean",
"duration",
"of",
"grade",
"3",
"+",
"neutropenia",
"(",
"neutrophil",
"count",
"<",
"1.0",
"×",
"10",
"(",
"9",
")",
"/l",
")",
"was",
"2.09",
",",
"1.53",
"and",
"1.73",
"days",
"in",
"patients",
"who",
"received",
"pegfilgrastim",
"60",
",",
"100",
"and",
"120",
"µg",
"/",
"kg",
"/",
"cycle",
",",
"respectively",
",",
"and",
"1.69",
"days",
"in",
"patients",
"who",
"received",
"5",
"µg",
"/",
"kg",
"/",
"day",
"filgrastim",
"(",
"P",
"=",
"0.043",
")",
".",
"The",
"incidence",
"of",
"grade",
"3",
"+",
"neutropenia",
"was",
"76",
",",
"83",
"and",
"74",
"%",
"for",
"doses",
"of",
"pegfilgrastim",
"and",
"90",
"%",
"for",
"filgrastim",
"(",
"P",
"=",
"0.409",
")",
".",
"The",
"results",
"for",
"febrile",
"neutropenia",
",",
"time",
"to",
"neutrophil",
"recovery",
"and",
"neutrophil",
"profile",
"were",
"also",
"not",
"significantly",
"different",
"between",
"arms",
".",
"The",
"safety",
"profiles",
"of",
"pegfilgrastim",
"and",
"filgrastim",
"were",
"similar",
".",
"A",
"single",
"dose",
"of",
"100",
"µg",
"/",
"kg",
"once",
"-",
"per",
"-",
"cycle",
"administration",
"of",
"pegfilgrastim",
"provided",
"neutrophil",
"support",
"and",
"a",
"safety",
"profile",
"comparable",
"to",
"daily",
"subcutaneous",
"injections",
"of",
"filgrastim",
"in",
"Chinese",
"breast",
"cancer",
"patients",
"receiving",
"TAC",
"chemotherapy",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
0,
0,
19,
0,
11,
9,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
33,
0,
33,
34,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
35,
36,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
29,
0,
29,
0,
29,
30,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
21,
22,
22,
22,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
95 | [
"Randomized",
"sham",
"-",
"controlled",
"pilot",
"trial",
"of",
"weekly",
"electro",
"-",
"acupuncture",
"for",
"the",
"prevention",
"of",
"taxane",
"-",
"induced",
"peripheral",
"neuropathy",
"in",
"women",
"with",
"early",
"stage",
"breast",
"cancer",
".",
"To",
"investigate",
"the",
"effect",
"of",
"electro",
"-",
"acupuncture",
"(",
"EA",
")",
"as",
"a",
"non",
"-",
"pharmacological",
"intervention",
"to",
"prevent",
"or",
"reduce",
"chemotherapy",
"-",
"induced",
"peripheral",
"neuropathy",
"(",
"CIPN",
")",
"in",
"breast",
"cancer",
"patients",
"undergoing",
"chemotherapy",
"of",
"taxane",
".",
"Women",
"with",
"stage",
"I",
"-",
"III",
"breast",
"cancer",
"scheduled",
"to",
"receive",
"taxane",
"therapy",
"were",
"randomized",
"to",
"receive",
"a",
"standardized",
"protocol",
"of",
"12",
"true",
"or",
"sham",
"EA",
"(",
"SEA",
")",
"weekly",
"treatments",
"concurrent",
"with",
"taxane",
"treatment",
".",
"Subjects",
"completed",
"the",
"Brief",
"Pain",
"Inventory",
"-",
"Short",
"Form",
"(",
"BPI",
"-",
"SF",
")",
",",
"Functional",
"Assessment",
"of",
"Cancer",
"Therapy",
"-",
"Taxane",
"neurotoxicity",
"subscale",
"(",
"FACT",
"-",
"NTX",
")",
",",
"and",
"other",
"assessments",
"at",
"baseline",
"and",
"weeks",
"6",
",",
"12",
",",
"and",
"16",
".",
"A",
"total",
"of",
"180",
"subjects",
"were",
"screened",
",",
"63",
"enrolled",
"and",
"48",
"completed",
"week",
"16",
"assessments",
".",
"Mean",
"age",
"was",
"50",
"with",
"25",
"%",
"white",
",",
"25",
"%",
"black",
",",
"and",
"43",
"%",
"Hispanic",
";",
"52",
"%",
"had",
"no",
"prior",
"chemotherapy",
".",
"At",
"week",
"12",
",",
"both",
"groups",
"reported",
"an",
"increase",
"in",
"mean",
"BPI",
"-",
"SF",
"worst",
"pain",
"score",
",",
"but",
"no",
"mean",
"differences",
"were",
"found",
"between",
"groups",
"(",
"SEA",
"2.8",
"vs.",
"EA",
"2.6",
",",
"P",
"=",
".",
"86",
")",
".",
"By",
"week",
"16",
",",
"the",
"SEA",
"group",
"returned",
"to",
"baseline",
",",
"while",
"the",
"EA",
"group",
"continued",
"to",
"worsen",
"(",
"SEA",
"1.7",
"vs.",
"EA",
"3.4",
",",
"P",
"=",
".",
"03",
")",
".",
"The",
"increase",
"in",
"BPI",
"-",
"SF",
"worst",
"pain",
"score",
"was",
"1.62",
"points",
"higher",
"in",
"the",
"EA",
"group",
"than",
"in",
"the",
"SEA",
"group",
"at",
"week",
"16",
"(",
"P",
"=",
".",
"04",
")",
".",
"In",
"a",
"randomized",
",",
"sham",
"-",
"controlled",
"trial",
"of",
"EA",
"for",
"prevention",
"of",
"taxane",
"-",
"induced",
"CIPN",
",",
"there",
"were",
"no",
"differences",
"in",
"pain",
"or",
"neuropathy",
"between",
"groups",
"at",
"week",
"12",
".",
"Of",
"concern",
",",
"subjects",
"on",
"EA",
"had",
"a",
"slower",
"recovery",
"than",
"SEA",
"subjects",
".",
"Future",
"studies",
"should",
"focus",
"on",
"EA",
"for",
"treatment",
"as",
"opposed",
"to",
"prevention",
"of",
"CIPN",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
0,
0,
0,
0,
13,
14,
14,
14,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
1,
0,
0,
1,
0,
0,
0,
0,
0,
7,
8,
8,
8,
0,
0,
0,
11,
0,
0,
0,
11,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
0,
35,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
33,
0,
0,
35,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
96 | [
"Prescribing",
"tamoxifen",
"in",
"primary",
"care",
"for",
"the",
"prevention",
"of",
"breast",
"cancer",
":",
"a",
"national",
"online",
"survey",
"of",
"GPs",
"'",
"attitudes",
".",
"The",
"cancer",
"strategy",
"for",
"England",
"(",
"2015",
"-",
"2020",
")",
"recommends",
"GPs",
"prescribe",
"tamoxifen",
"for",
"breast",
"cancer",
"primary",
"prevention",
"among",
"women",
"at",
"increased",
"risk",
".",
"To",
"investigate",
"GPs",
"'",
"attitudes",
"towards",
"prescribing",
"tamoxifen",
".",
"In",
"an",
"online",
"survey",
",",
"GPs",
"in",
"England",
",",
"Northern",
"Ireland",
",",
"and",
"Wales",
"(",
"n",
"=",
"928",
")",
"were",
"randomised",
"using",
"a",
"2",
"×",
"2",
"between",
"-",
"subjects",
"design",
"to",
"read",
"one",
"of",
"four",
"vignettes",
"describing",
"a",
"healthy",
"patient",
"seeking",
"a",
"tamoxifen",
"prescription",
".",
"In",
"the",
"vignette",
",",
"the",
"hypothetical",
"patient",
"'s",
"breast",
"cancer",
"risk",
"(",
"moderate",
"versus",
"high",
")",
"and",
"the",
"clinician",
"initiating",
"the",
"prescription",
"(",
"GP",
"prescriber",
"versus",
"secondary",
"care",
"clinician",
"[",
"SCC",
"]",
"prescriber",
")",
"were",
"manipulated",
"in",
"a",
"1",
":1",
":1",
":1",
"ratio",
".",
"Outcomes",
"were",
"willingness",
"to",
"prescribe",
",",
"comfort",
"discussing",
"harms",
"and",
"benefits",
",",
"comfort",
"managing",
"the",
"patient",
",",
"factors",
"affecting",
"the",
"prescribing",
"decision",
",",
"and",
"awareness",
"of",
"tamoxifen",
"and",
"the",
"National",
"Institute",
"for",
"Health",
"and",
"Care",
"Excellence",
"(",
"NICE",
")",
"guideline",
"CG",
"164",
".",
"Half",
"(",
"51.7",
"%",
")",
"of",
"the",
"GPs",
"knew",
"tamoxifen",
"can",
"reduce",
"breast",
"cancer",
"risk",
",",
"and",
"one",
"-",
"quarter",
"(",
"24.1",
"%",
")",
"were",
"aware",
"of",
"NICE",
"guideline",
"CG",
"164",
".",
"Responders",
"asked",
"to",
"initiate",
"prescribing",
"(",
"GP",
"prescriber",
")",
"were",
"less",
"willing",
"to",
"prescribe",
"tamoxifen",
"than",
"those",
"continuing",
"a",
"prescription",
"initiated",
"in",
"secondary",
"care",
"(",
"SCC",
"prescriber",
")",
"(",
"68.9",
"%",
"versus",
"84.6",
"%",
",",
"P",
"<",
"0.001",
")",
".",
"The",
"GP",
"prescribers",
"reported",
"less",
"comfort",
"discussing",
"tamoxifen",
"(",
"53.4",
"%",
"versus",
"62.5",
"%",
",",
"P",
"=",
"0.01",
")",
".",
"GPs",
"willing",
"to",
"prescribe",
"were",
"more",
"likely",
"to",
"be",
"aware",
"of",
"the",
"NICE",
"guideline",
"(",
"P",
"=",
"0.039",
")",
"and",
"to",
"have",
"acknowledged",
"the",
"benefits",
"of",
"tamoxifen",
"(",
"P",
"<",
"0.001",
")",
",",
"and",
"were",
"less",
"likely",
"to",
"have",
"considered",
"its",
"off",
"-",
"licence",
"status",
"(",
"P",
"<",
"0.001",
")",
".",
"Initiating",
"tamoxifen",
"prescriptions",
"for",
"preventive",
"therapy",
"in",
"secondary",
"care",
"before",
"asking",
"GPs",
"to",
"continue",
"the",
"patient",
"'s",
"care",
"may",
"overcome",
"some",
"prescribing",
"barriers",
"."
] | [
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
17,
18,
18,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
15,
16,
0,
0,
15,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
19,
20,
20,
20,
20,
20,
20,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
0,
29,
30,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
97 | [
"Chemotherapy",
"(",
"CT",
")",
"and",
"hormonotherapy",
"(",
"HT",
")",
"as",
"neoadjuvant",
"treatment",
"in",
"luminal",
"breast",
"cancer",
"patients",
":",
"results",
"from",
"the",
"GEICAM",
"/",
"2006",
"-",
"03",
",",
"a",
"multicenter",
",",
"randomized",
",",
"phase",
"-",
"II",
"study",
".",
"Luminal",
"breast",
"cancer",
"is",
"a",
"highly",
"endocrine",
"responsive",
"disease",
".",
"However",
",",
"the",
"therapeutic",
"benefit",
"of",
"chemotherapy",
"(",
"CT",
")",
"in",
"this",
"population",
"is",
"not",
"fully",
"characterized",
".",
"This",
"study",
"investigates",
"the",
"value",
"of",
"CT",
"and",
"hormone",
"therapy",
"(",
"HT",
")",
"in",
"luminal",
"breast",
"cancer",
"patients",
"in",
"the",
"neoadjuvant",
"setting",
".",
"Patients",
"with",
"operable",
"breast",
"cancer",
"and",
"immunophenotypically",
"defined",
"luminal",
"disease",
"(",
"ER+",
"/",
"PR+",
"/",
"HER",
"2",
"-",
"/",
"cytokeratin",
"8",
"/",
"18",
"+",
")",
"were",
"recruited",
".",
"Patients",
"were",
"randomized",
"to",
"CT",
"(",
"epirubicin",
"90",
"mg",
"/",
"m",
"(",
"2",
")",
"plus",
"cyclophosphamide",
"600",
"mg",
"/",
"m",
"(",
"2",
")",
"4",
"cycles",
"followed",
"by",
"docetaxel",
"100",
"mg",
"/",
"m",
"(",
"2",
")",
"4",
"cycles",
"[",
"EC",
"-",
"T",
"]",
")",
"or",
"HT",
"(",
"exemestane",
"25",
"mg",
"daily",
"24",
"weeks",
"[",
"combined",
"with",
"goserelin",
"in",
"premenopausal",
"patients",
"]",
")",
".",
"The",
"primary",
"end",
"point",
"was",
"the",
"clinical",
"response",
"measured",
"by",
"magnetic",
"resonance",
"imaging",
".",
"Ninety",
"-",
"five",
"patients",
"were",
"randomized",
"(",
"47",
"CT",
",",
"48",
"HT",
")",
".",
"The",
"clinical",
"response",
"rate",
"was",
"66",
"%",
"for",
"CT",
"and",
"48",
"%",
"for",
"HT",
"(",
"P",
"=",
"0.075",
")",
".",
"We",
"performed",
"an",
"unplanned",
"analysis",
"based",
"on",
"Ki",
"67",
"levels",
"(",
"cut",
"-",
"off",
"of",
"10",
"%",
")",
".",
"Similar",
"clinical",
"response",
"was",
"seen",
"between",
"arms",
"in",
"patients",
"with",
"low",
"Ki",
"67",
"(",
"CT",
":",
"63",
"%",
",",
"HT",
":",
"58",
"%",
";",
"P",
"=",
"0.74",
")",
";",
"patients",
"with",
"high",
"Ki",
"67",
"had",
"a",
"better",
"response",
"with",
"CT",
"(",
"67",
"versus",
"42",
"%",
";",
"P",
"=",
"0.075",
")",
".",
"Grade",
"3",
"/",
"4",
"toxicity",
"was",
"more",
"frequent",
"with",
"CT",
".",
"Luminal",
"immunophenotype",
"is",
"not",
"enough",
"to",
"identify",
"patients",
"who",
"do",
"not",
"benefit",
"from",
"neoadjuvant",
"CT",
".",
"Luminal",
"patients",
"with",
"low",
"proliferation",
"index",
"could",
"potentially",
"avoid",
"CT",
"."
] | [
17,
18,
18,
18,
0,
19,
20,
20,
20,
0,
0,
0,
0,
9,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
0,
0,
0,
0,
0,
0,
1,
2,
2,
0,
0,
0,
0,
3,
0,
0,
5,
0,
0,
0,
0,
21,
22,
22,
0,
29,
30,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
29,
30,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
29,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
98 | [
"Anthracycline",
"could",
"be",
"essential",
"for",
"triple",
"-",
"negative",
"breast",
"cancer",
":",
"A",
"randomised",
"phase",
"II",
"study",
"by",
"the",
"Kanagawa",
"Breast",
"Oncology",
"Group",
"(",
"KBOG",
")",
"1101",
".",
"It",
"is",
"important",
"to",
"determine",
"whether",
"anthracycline",
"-",
"containing",
"regimens",
"or",
"taxane",
"-",
"containing",
"regimens",
"are",
"more",
"effective",
"in",
"individual",
"patients",
".",
"The",
"present",
"study",
"compared",
"the",
"efficacy",
"of",
"six",
"cycles",
"of",
"docetaxel",
"and",
"cyclophosphamide",
"(",
"TC",
"6",
")",
"with",
"that",
"of",
"three",
"cycles",
"of",
"5",
"-fluorouracil",
",",
"epirubicin",
"and",
"cyclophosphamide",
"followed",
"by",
"docetaxel",
"(",
"FEC",
"-",
"D",
")",
"in",
"Japanese",
"patients",
"with",
"hormone",
"receptor",
"(",
"HR",
")",
"-negative",
"breast",
"cancer",
"(",
"BC",
")",
"to",
"identify",
"subtypes",
"requiring",
"anthracycline",
"treatment",
".",
"The",
"study",
"included",
"103",
"patients",
"with",
"operable",
"HR",
"-",
"negative",
"BC",
".",
"Of",
"these",
"patients",
"53",
"received",
"FEC",
"-",
"D",
"and",
"50",
"received",
"TC",
"6",
".",
"The",
"primary",
"endpoint",
"was",
"pathological",
"complete",
"response",
"(",
"pCR",
")",
".",
"The",
"secondary",
"endpoints",
"were",
"safety",
",",
"breast",
"-",
"conserving",
"surgery",
",",
"disease",
"-",
"free",
"survival",
"(",
"DFS",
")",
"and",
"overall",
"survival",
"(",
"OS",
")",
".",
"The",
"predictive",
"factors",
"for",
"each",
"regimen",
"were",
"evaluated",
".",
"Of",
"the",
"103",
"patients",
",",
"97",
"completed",
"the",
"study",
"(",
"FEC",
"-",
"D",
",",
"50",
"patients",
";",
"TC",
"6",
",",
"47",
"patients",
")",
".",
"The",
"pCR",
"rate",
"was",
"higher",
"with",
"FEC",
"-",
"D",
"(",
"36",
"%",
")",
"than",
"with",
"TC",
"6",
"(",
"25.5",
"%",
")",
";",
"however",
",",
"the",
"difference",
"was",
"not",
"significant",
"(",
"P",
"=",
"0.265",
")",
".",
"TC",
"6",
"was",
"safer",
"than",
"FEC",
"-",
"D",
",",
"as",
"the",
"adverse",
"events",
"with",
"docetaxel",
"in",
"the",
"FEC",
"-",
"D",
"regimen",
"were",
"similar",
"to",
"those",
"with",
"the",
"TC",
"6",
"regimen",
".",
"Among",
"patients",
"with",
"basal",
"BC",
",",
"the",
"pCR",
"rate",
"was",
"significantly",
"higher",
"with",
"FEC",
"-",
"D",
"(",
"42.9",
"%",
")",
"than",
"with",
"TC",
"6",
"(",
"13.6",
"%",
";",
"P",
"=",
"0.033",
")",
".",
"Among",
"patients",
"with",
"triple",
"-",
"negative",
"breast",
"cancer",
"(",
"TNBC",
")",
",",
"the",
"DFS",
"and",
"OS",
"were",
"significantly",
"better",
"with",
"FEC",
"-",
"D",
"than",
"with",
"TC",
"6",
"(",
"P",
"=",
"0.016",
"and",
"P",
"=",
"0.034",
",",
"respectively",
")",
".",
"TC",
"6",
"was",
"not",
"as",
"effective",
"as",
"FEC",
"-",
"D",
"for",
"treating",
"HR",
"-",
"negative",
"BC",
",",
"as",
"TC",
"6",
"was",
"not",
"sufficient",
"to",
"treat",
"TNBC",
",",
"particularly",
"the",
"basal",
"subtype",
".",
"Our",
"findings",
"suggest",
"that",
"anthracyclines",
"are",
"better",
"treatment",
"options",
"than",
"taxanes",
"for",
"basal",
"BC",
"."
] | [
17,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
15,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
11,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
19,
20,
20,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
23,
0,
23,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
3,
0,
0,
0,
0,
0,
5,
0,
0,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
0,
0,
21,
22,
0,
0,
0,
0,
0,
0,
0,
0,
29,
30,
0,
0,
0,
0,
0,
0,
31,
32,
0,
0,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
22,
22,
22,
0,
0,
21,
0,
21,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |
99 | [
"Randomised",
"controlled",
"trial",
"comparing",
"hypnotherapy",
"versus",
"gabapentin",
"for",
"the",
"treatment",
"of",
"hot",
"flashes",
"in",
"breast",
"cancer",
"survivors",
":",
"a",
"pilot",
"study",
".",
"To",
"compare",
"the",
"efficacy",
"of",
"hypnotherapy",
"versus",
"gabapentin",
"for",
"the",
"treatment",
"of",
"hot",
"flashes",
"in",
"breast",
"cancer",
"survivors",
",",
"and",
"to",
"evaluate",
"the",
"feasibility",
"of",
"conducting",
"a",
"clinical",
"trial",
"comparing",
"a",
"drug",
"with",
"a",
"complementary",
"or",
"alternative",
"method",
"(",
"CAM",
")",
".",
"Prospective",
"randomised",
"trial",
".",
"Breast",
"health",
"centre",
"of",
"a",
"tertiary",
"care",
"centre",
".",
"15",
"women",
"with",
"a",
"personal",
"history",
"of",
"breast",
"cancer",
"or",
"an",
"increased",
"risk",
"of",
"breast",
"cancer",
"who",
"reported",
"at",
"least",
"one",
"daily",
"hot",
"flash",
".",
"Gabapentin",
"900",
"mg",
"daily",
"in",
"three",
"divided",
"doses",
"(",
"control",
")",
"compared",
"with",
"standardised",
"hypnotherapy",
".",
"Participation",
"lasted",
"8",
"weeks",
".",
"The",
"primary",
"endpoints",
"were",
"the",
"number",
"of",
"daily",
"hot",
"flashes",
"and",
"hot",
"flash",
"severity",
"score",
"(",
"HFSS",
")",
".",
"The",
"secondary",
"endpoint",
"was",
"the",
"Hot",
"Flash",
"Related",
"Daily",
"Interference",
"Scale",
"(",
"HFRDIS",
")",
".",
"27",
"women",
"were",
"randomised",
"and",
"15",
"(",
"56",
"%",
")",
"were",
"considered",
"evaluable",
"for",
"the",
"primary",
"endpoint",
"(",
"n=",
"8",
"gabapentin",
",",
"n=",
"7",
"hypnotherapy",
")",
".",
"The",
"median",
"number",
"of",
"daily",
"hot",
"flashes",
"at",
"enrolment",
"was",
"4.5",
"in",
"the",
"gabapentin",
"arm",
"and",
"5",
"in",
"the",
"hypnotherapy",
"arm",
".",
"HFSS",
"scores",
"were",
"7.5",
"in",
"the",
"gabapentin",
"arm",
"and",
"10",
"in",
"the",
"hypnotherapy",
"arm",
".",
"After",
"8",
"weeks",
",",
"the",
"median",
"number",
"of",
"daily",
"hot",
"flashes",
"was",
"reduced",
"by",
"33.3",
"%",
"in",
"the",
"gabapentin",
"arm",
"and",
"by",
"80",
"%",
"in",
"the",
"hypnotherapy",
"arm",
".",
"The",
"median",
"HFSS",
"was",
"reduced",
"by",
"33.3",
"%",
"in",
"the",
"gabapentin",
"arm",
"and",
"by",
"85",
"%",
"in",
"the",
"hypnotherapy",
"arm",
".",
"HFRDIS",
"scores",
"improved",
"by",
"51.6",
"%",
"in",
"the",
"gabapentin",
"group",
"and",
"by",
"55.2",
"%",
"in",
"the",
"hypnotherapy",
"group",
".",
"There",
"were",
"no",
"statistically",
"significant",
"differences",
"between",
"groups",
".",
"Hypnotherapy",
"and",
"gabapentin",
"demonstrate",
"efficacy",
"in",
"improving",
"hot",
"flashes",
".",
"A",
"definitive",
"trial",
"evaluating",
"traditional",
"interventions",
"against",
"CAM",
"methods",
"is",
"feasible",
",",
"but",
"not",
"without",
"challenges",
".",
"Further",
"studies",
"aimed",
"at",
"defining",
"evidence",
"-",
"based",
"recommendations",
"for",
"CAM",
"are",
"necessary",
".",
"clinicaltrials",
".",
"gov",
"(",
"NCT",
"00711529",
")",
"."
] | [
0,
0,
0,
0,
17,
0,
19,
0,
0,
0,
0,
13,
14,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
1,
9,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
10,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
0,
23,
24,
24,
24,
24,
24,
24,
0,
0,
0,
0,
0,
0,
23,
24,
24,
24,
24,
24,
24,
24,
24,
0,
1,
0,
0,
0,
0,
1,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
5,
0,
0,
0,
3,
0,
0,
0,
0,
21,
22,
22,
22,
22,
22,
22,
22,
0,
39,
0,
0,
0,
0,
0,
37,
0,
0,
0,
0,
0,
21,
22,
0,
39,
0,
0,
0,
0,
0,
37,
0,
0,
0,
0,
0,
21,
22,
22,
0,
0,
21,
22,
22,
22,
22,
22,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
37,
38,
0,
0,
0,
0,
0,
0,
21,
22,
0,
0,
0,
39,
40,
0,
0,
0,
0,
0,
0,
37,
38,
0,
0,
0,
0,
0,
21,
22,
22,
0,
35,
36,
0,
0,
0,
0,
0,
0,
37,
38,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0,
0
] |