bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of vitamin E in the prevention of cancer: Meta-analysis of randomized controlled trials
Authors: Alkhenizan A. , Hafez K.
Published: March 2020

1017

Background: Several in vitro studies showed antioxidant vitamins to have a significant protective effect against cancer. We did a meta-analysis of Randomized Controlled Trials (RCTs) to evaluate the role of vitamin E supplements in the prevention of Cancer in adults Methods: We included RCTs, in which outcomes of the intake of vitamin E supplement alone or with other supplements, were compared to a control group.The primary outcomes were total mortality, cancer mortality, total incidence of Cancer, incidence of Lung, stomach, esophageal, pancreatic, prostate, breast and thyroid cancers. All identified trials were reviewed independently by the two reviewers to determine whether trials should be included or excluded. The quality of all included studies was scored independently by the two reviewers. RevMan, version 4.2 was used for the data analysis. Results: Twelve studies met inclusion criteria, including 167025 participants. There were no statistically significant differences in total mortality (RR 0.99; 95%CI 0.96–1.03), cancer incidence (OR 0.96; 95%CI 0.92, 1.01), and cancer mortality (OR 1.00; 95%CI 0.96–1.03) among the different groups of patients included in this meta-analysis. Vitamin E did not reduce the incidence of any type of cancer that was available for analysis; However there was a statistically significant reduction in the incidence of prostate cancer in patients receiving vitamin E, RR 0.85 [0.73–0.96, NNT=500]. Conclusions: Vitamin E supplementation was not associated with a reduction in total mortality or cancer incidence, and cancer mortality, but it was associated with a statistically significant reduction in the incidence of prostate cancer. Vitamin E can be used in the prevention of Prostate cancer in men who are at high risk of prostate cancer.

No significant financial relationships to disclose.
Preferences for cancer prevention strategies (CPS) in women with hereditary nonpolyposis colectal cancer (HNPCC)
Authors: Sun C. C. , Peterson S. K. , White K. G. , Watts B. G. , Daniels M. S. , Boyd-Rogers S. G. , Schmeler K. M. , Bodurka D. C. , Lu K. H.
Published: March 2020

1018

Background: Women with HNPCC have 40–60% lifetime risk of endometrial and colon cancer (CA) and 10–12% risk of ovarian CA. Because CPS have significant QOL implications, understanding how women evaluate CPS and personal risks of CA may facilitate physician and pt communication for medical decision making in this group of pts. Methods: Using the visual analog scale (VAS) and standard gamble (SG), women with HNPCC or with a family history (FHx) that fulfilled Amsterdam II criteria were asked to: 1) score CPS from 0.0=worst to 1.0=best; and 2) state the % personal risk of CA they would need to have in order to undergo each CPS. CPS included oral contraceptives ± COX-2 inhibitors (OC ± COX2); endometrial biopsy/transvaginal ultrasound/CA125 ± colonoscopy (Bx/US ± CSPY); pre- and post-menopausal total abdominal hysterectomy/oophorectomy ± subtotal colectomy (TAH/BSO ± COL). Results: To date, 32 women have enrolled (median age=38.4 yrs). Bx/US + CSPY was rated most favorably (0.95) followed by OC, Bx/US, and CSPY(.90). Pre-menopausal TAH/BSO, COL, and TAH/BSO+ COL had the least favorable ratings (0.50, 0.30, and 0.25, respectively). Women accepted non-surgical CPS if their personal risk of CA was at least 30%; pre- and post-menopausal TAH/BSO if the personal risk of CA was at least 73% and 50%, respectively. Women accepted COL and TAH/BSO + COL if their risks of CA were at least 78% and 80%, respectively. Women without FHx of HNPCC-gynecologic (GYN) CA would participate in all CPS more readily than women with FHx of HNPCC-GYN CA. Specifically, to accept COX2, women without FHx of HNPCC-GYN CA would do to if their personal CA risk was at least 10% compared to a 30% risk for women in the 2nd group (p=.04). For the 2 groups, risks for Bx/US, pre-menopausal TAH/BSO, post-menopausal TAH/BSO, TAH/BSO + COL and COL were 20% vs 30% (p=.06), 40% vs 80% (p=.03), 30% vs 55% (p=.02), 65% vs 80% (p=.06), and 80% vs 100% (p=.01), respectively. Conclusions: Our data indicate that women without FHx of HNPCC-GYN CA are more willing to undergo chemoprevention, screening and prophylactic surgery for HNPCC CA compared to women with a FHx of HNPCC-GYN CA. This may be due to the perception of a more favorable clinical outcome associated with endometrial CA, the more common of the HNPCC-GYN CA.

No significant financial relationships to disclose.
Patterns of diagnosis for colorectal cancer (CRC): Screening detected versus symptomatic presentation
Authors: Smiljanic S. R. , Gill S.
Published: March 2020

1023

Background: Colorectal cancer (CRC) is a leading cause of cancer death in North America; studies have shown that screening improves survival. Conducted in British Columbia, Canada, this study was conducted to identify the proportion of screening-eligible patients with sporadic CRC who are detected by screening tests versus symptomatic presentation,and to compare baseline patient and tumor characteristics of these two groups. Methods: This retrospective cohort study identified 571 cases via the BC Cancer Registry of patients age 50 years and older presenting with first diagnosis of invasive CRC between Nov. 2002 and Apr. 2003. Patients with non-adenocarcinoma histology, HNPCC or FAP were not included. Self completed questionnaires were mailed to all patients to capture: prior screening history, screening versus symptomatic presentation, and demographic information. All respondents charts were then reviewed to corroborate screening information, and to obtain pathological information including TNM stage, grade and site (proximal versus distal colon versus rectal). Results: Of 212 eligible respondents (37% response), only 14 of 212 (6.6%) patients with a new CRC were detected via screening versus 198 of 212 (93.4%) presenting with symptoms. Respondents were average age at diagnosis 69 years, 59% male, 91% Caucasian, 37%rectal, and 18% M1 at diagnosis. No significant differences in the age, gender, ethnicity, socioeconomic status, tumour stage and site were detected between the screened versus symptomatic groups. Only 33 of 212 patients (15.6%) reported ever having a screening test. 19 of 198 cancers (9.6%) were diagnosed by symptomatic presentation despite a compliant screening history. Conclusion: Despite universal health-care access in British Columbia, only 7% of patients with a new diagnosis of CRC were detected via a screening test. Furthermore, only 15% of screening-eligible respondents have ever been screened. There were no differences in patient demographics or stage of disease at presentation but numbers in the screening cohort were limited. Significant effort is required to increase knowledge and compliance for CRC screening.

No significant financial relationships to disclose.
Incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel
Authors: Berliere M. , Dalenc F. , Malingret N. , Vindevogel A. , Kerger J. , Roche H. , Symann M. , Donnez J. , Machiels P J.
Published: March 2020

10517

Background: The objective of this study was to determine the incidence of reversible amenorrhea in women with early-stage breast cancer undergoing adjuvant anthracyclin-based chemotherapy with or without docetaxel. Methods: We studied the amenorrhea duration induced by 2 chemotherapy regimens. The first arm (6FEC) consisted in the administration of 6 cycles of FEC100 (5-Fluorouracil 500 mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2, day 1, every 3 weeks) and the second arm (3FEC/3D) in the administration of 3 cycles of FEC100 followed by 3 cycles of Docetaxel (100 mg/m2, day 1, every 3 weeks). Some of these patients (N = 121, 78%) were treated in the PACS01 trial that was designed to evaluate the impact of the sequential addition of docetaxel to FEC100 on disease-free survival for patients with node positive, operable breast cancer. Other patients (N = 33.22%) were patients treated with the same regimens after the inclusion period of PACS01. Reversible amenorrhea was defined as a recovery of regular menses and -when available (101 patients)- premenopausal hormonal values (minimum 2 tests at 3 months interval) in the year following the end of chemotherapy infusion. Results: 154 pre-menopausal patients were included: 84 were treated in the 6FEC and 70 in the 3FEC/3D. Median age was 43.5 (28–58) and 44 (29–53), respectively. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was not different between the two groups, 6FEC: 93% and 3FEC/3D: 92.5%. In the year following the end of chemotherapy, more patients recovered regular menses in the 3FEC/3D arm compared to the 6FEC arm: 35.5% (25/70) versus 23.7% (20/84) (p = 0.019). For the 101 for which hormonal values were available, more patients recovered premenopausal hormonal values in the 3FEC/3D arm: 42% (18/42) versus 29% (17/59) (p < 0.01). Conclusions: Our study suggests that it could be interesting to record the menopausal status at different time points after the end of chemotherapy. In addition, the survival advantage in the PACS01 trial in favor of the 3FEC/3D arm was observed only for women over the age of 50 and not for women younger than 50. In this context, the clinical relevance of reversible amenorrhea warrants further investigation.

No significant financial relationships to disclose.
Is histology (His) relevant in adjuvant (Adj)/neoadjuvant (NA) therapy of breast cancer (BC)?
Authors: Katz A. , Saad E. D. , Pusztai L.
Published: March 2020

10541

Background: Invasive lobular carcinoma (ILC) constitutes 10–15% of cases of invasive BC. In ongoing NCI-sponsored, randomized trials (RT) of early BC, His is not a stratification factor, despite the suggestion that ILC might have distinct clinical behavior and gene expression profile. Compared with invasive ductal carcinoma (IDC), ILC is more frequently of lower grade and positive for estrogen receptor (ER). Methods: We reviewed the literature to evaluate the effect of His on outcome of Adj and NA therapy, by quantifying its impact on the pathologic response (pCR) rate to NA chemotherapy (CT), and on the results of adjuvant trials. We also compiled retrospective series analyzing pCR to NA CT according to His. Results: We retrieved 16 RT (8 phase III, 8 phase II) of NA therapy; 11 compared CT regimens, 3 regimens that contained CT and hormone therapy (HT), and 2 HT only. None of the RT used His for stratification; 5 studies described His at randomization, but only 1 provided information on pCR rate to CT according to His (Dieras et al, 4.0% for ILC, 8.3% for IDC). Compiled results of 6 retrospective series which included nearly 3,000 patients (PTS) showed a pCR rate of 1.7% (6 of 354) in ILC PTS and of 11.6% (300 of 2584) in IDC PTS (P < 0.01). Of 39 phase III RT of Adj CT, 7 compared CT vs HT, 14 CT vs CT + HT, 11 HT vs HT + CT, and 7 CT vs HT vs CT + HT. Of the 39 RT, only 4 described His in demography (9%, 9%, 10% and 12% of PTS participating in these 4 RT were ILC), but none analyzed results according to His. Conclusions: We suggest that the role of CT in early ILC is not clear. The pCR rate is significantly lower in ILC PTS treated with NA CT. It is also not clear if His is an independent predictive factor or a marker of grade/ER expression. The specific value of CT in the Adj treatment of ILC PTS has not been adressed in the Adj RT. Past and current, ongoing RT of Adj CT do not stratify PTS according to His neither evaluate the results according to His. Given the potential therapeutic implications, we suggest that the role of His should be more thoroughly investigated in future RT in order to define the appropriate effectiveness of CT and HT in the treatment of ILC PTS, so that possible overtreatment of ILC PTS with CT might be avoided.

No significant financial relationships to disclose.
Phase II study of sequentially administered mitomycin (MMC) and irinotecan (CPT-11) in patients (pts) with metastatic breast cancer (MBC)
Authors: Mrozek E. , Kolesar J. , Allen J. , Young D. , Angus D. , Kendra K. , Rhoades C. A. , Villalona-Calero M. A. , Shapiro C. L.
Published: March 2020

10542

Background: MMC and CPT-11 are synergistic in preclinical studies, as MMC increases expression of Topoisomerase I (Topo I), the target of CPT-11. Three out of 5 heavily pretreated MBC pts benefited from MMC and CPT-11 in a phase I trial. We designed a phase II trial of this combination in MBC pts and hypothesized that increased Topo I expression in peripheral blood mononuclear cells (PBMC) would correlate with longer time to progression (TTP). Methods: Pt eligibility: ECOG PS 2 or less; no more than 2 prior chemotherapy regimens for MBC; adequate organ function; measurable and non-measurable disease were permitted. Treatment: intravenous (IV) MMC-6 mg/m2 on day 1 and IV CPT-11–125 mg/m2 on days 2 and 8 every 28 days. Genotyping of NQ01 (enzyme that activates MMC) was evaluated by pyrosequencing; Topo I gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) was evaluated in PBMC pretreatment, 24 hrs, 48 hrs, and 8 days after MMC. Results: Thirty-two pts enrolled with the following characteristics: median age 50 years (range 29–73); median PS 0 (range 0–2); postmenopausal 29 (91%) pts; estrogen receptor (ER) negative 14 (44%) pts; HER-2/neu 3+ by IHC 7 (22%) pts, and 10 (31%) pts were ER(−), PR(−) and HER-2/neu (−). Six (19%) pts had no prior chemotherapy; 7 (22%)-1 prior regimen; and 19 (59%)-2 prior regimens. Pts received a median of 4 cycles (range 1–12). Four (12%) pts experienced grade 4 toxicity (1-neutropenia without fever, 1-abdominal pain, 1-pulmonary embolism, and 1-diarrhea). The most common grade 3 toxicities were neutropenia in 13(41%) pts, nausea in 7 (22%) pts, diarrhea in 6 (19%) pts, fatigue in 5 (16%) pts, and thrombocytopenia in 2 (6%) pts. Median TTP was 4.7 months (95% CI, 4.0 to 5.4 months). For 10 triple negative pts the median TTP of 5.4 months was not different. Baseline and induced Topo I gene expression was greatest in NQ01 wild-type genotype, however, increased Topo I expression in PBMC was associated with shorter TTP. Conclusions: Sequential administration of MMC and CPT-11 had acceptable toxicities and antitumor activity. Our hypothesis that increased Topo I expression in PBMC correlates with longer TTP was incorrect.

No significant financial relationships to disclose.
Induced fluorescence of breast cancer in the mouse model: A simple technology to improve visualization of malignant tissue during breast cancer surgery
Authors: Chan A. D. , Luiken G. A. , Quigley M. M. , Xu M. , Hoffman R. M.
Published: March 2020

10557

Background: Accurate identification of all malignant tissue at the time of lumpectomy or mastectomy can at times be challenging. When positive margins are discovered, significant additional time and effort may be required by the surgeon to complete the initial procedure. Inducing the cancer cells to be fluorescent offers the potential to improve the surgeon’s ability to rapidly and accurately identify and excise the malignant tissue at the time of surgery. We have previously demonstrated the feasibility of inducing tumor fluorescence with fluorophore-tagged anti-tumor antigen antibodies using a human colon cancer cell line. We present here our recent results using a human breast cancer cell line in the nude mouse. Methods: A human breast cancer cell line, MDA-MB-468 known to express CA 15–3 was used. Breast cancer cells were subcutaneously implanted in 14 nude mice. Three to five weeks after injection, tumor nodules were easily visible and palpable. Using the tail vein method, mice were injected with fluorophore-tagged anti-CA 15–3 and were examined using a small animal imaging system with a 470 nm light source. Mice were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band-pass filter and were observed through filtered goggles. Results: Tumor nodules could be seen to fluoresce through the skin when illuminated with a 470 nm light source. When tumor nodules were exposed and examined with white light, the nodules could be seen but when illuminated with the 470 nm light source, tumor fluorescence allowed clear identification of nearby small tumor nodules and clear identification of tumor margins easily distinguishable from the normal tissue. Conclusions: For this technology to work, tumor antigens must be known and antibodies to these antigens available. It is easy to perform, requires no complex equipment or operator expertise and could be easily adapted to surgical oncology in any hospital setting. It has the potential to improve surgical accuracy in women undergoing initial lumpectomy or mastectomy as well as axillary lymph node dissection or sentinel node biopsy. In addition it could aid in the surgery of patients undergoing resection of isolated recurrent hepatic or pulmonary metastases.

No significant financial relationships to disclose.
Toll like receptor 3 expression and efficacy of adjuvant treatment with polyadenylic-polyuridylic acid in patients with axillary node positive breast cancer: Results from two randomized trials
Authors: André F. , Massard C. , Assi H. , Besse B. , Sabourin J. , Zitvogel L.
Published: March 2020

10563

Background: Toll like receptor 3 (TLR3) are transmembrane receptors involved in the cellular response to danger signal and specifically activated by double stranded RNA. Based on these data, we hypothesized that the TLR3 expression by tumor cells is associated with the efficacy of a treatment with double stranded RNA in cancer patients. Patients and Methods: TLR3 expression was assessed by immunohistochemistry in 336 patients with axillary node positive breast cancer. These patients were selected to have been included in two randomized trials that compared a post-operative administration of polyadenylic-polyuridylic acid (polyAU) to either no treatment (n = 174, trial I) or an adjuvant chemotherapy by CMF regimen (n = 162, trial II). In the trial II, locoregional and pelvic radiotherapy were given in the polyAU arm. Results: TLR3 was found to be overexpressed in 45 tumors (13%). Median follow-up were 23 and 17 years for living patients included in the trials I and II respectively. When the analysis focused on the first trial, the 20 year overall survival rates were 87% (95% CI: 53–97%) and 32% (95% CI: 12–63%) for patients with TLR3-overexpressing tumour treated (n = 8) or not (n = 11) with polyAU (p = 0.03). In the same trial, the 20 year overall survival rates were 43% (95% CI: 33–54%) and 35% (95% CI: 25–46%) for patients with TLR3-negative tumor treated (n = 81) or not (n = 74) with polyAU (p = 0.32). When the analysis focused on the Trial II, the 15 year overall survival were 62% (95% CI: 45%-91%) and 21% (95% CI: 8%-47%) for patients with TLR3-overexpressing tumors treated (n = 12) or not (n = 14) with polyAU (p = 0.005). In the same trial, 15 year overall survival rates were 31% (95% CI: 21%-42%) and 39% (95% CI: 28%-51%) for patients with TLR3-negative tumors treated (n = 66) or not (n = 70) with polyAU (p = 0.39). Conclusion: This study suggests that the post-operative administration of polyadenylic-polyuridylic acid improves outcome of patient with TLR3-overexpressing, node-positive breast cancer.

[Table: see text]
National HER2 testing program for breast cancer patients in Argentina
Authors: Frahm I.
Published: March 2020

10566

Background: In Argentina, before 2003 few pathologists performed HER2 testing, using different non-standardized Inmuno-Histo-Chemical (IHC) methods with dubious and non-reproducible results and also leaving some parts of the country without HER2 diagnosis Objective: HER2 has a key role in breast cancer management, so the aim of the study was to settle a National HER2 testing Program to permit access to standardized HER2 detection all over the country, and whenever possible, to determine hormonal receptors. Methods: In August 2003, 13 pathologists formed a cooperative group and created a national framework to train and set HER2 diagnostic centres in each country region. A coordinator responsible for coaching and evaluating centres and two technical consultants in charge of quality control and technique standardization were designated. In February 2004, the program was launched. Tumors were received from 82 oncologists and breast surgeons, using a private courier created “ad hoc”. HER2 was analyzed by IHC test between February 2004 and November 2005 and performed using policlonal antibody anti Her 2 (DAKO), microwave antigenic recovery, detection system EnVision (Dako) and developed with diaminobenzidine. Results were interpreted as HercepTest guidelines. ER/PR were screened by IHC analyses. Results: 2285 HER2 tests were performed: HER2 was over-expressed (score 3+) in 18% of tumors (408). 136 (6%) samples were score 2+, 407 (18%) score 1+ and 1334 (58%) score 0. In 1532/2285 (67%) of tumor specimens ER and PR status could be determined. Conclusions: Founding HER2 National Program allowed access to HER2 testing all over the country with a standardized and reproducible technique. HER2 prevalence in our sample (18%) is similar to those previously published. Although international algorithms recommend FISH assay to HER2 2+ tumors, our Program can not afford it. ER/PR expression were decreased significantly in HER2 3+ vs. HER2 - tumors: 53% vs. 64%: p = 0.002. HER2 3+ were associated with higher levels ER/PR: 38% vs. 24% in HER2 - tumors (p < 0.001).

[Table: see text]

No significant financial relationships to disclose.
A mathematical model to predict for pre-malignant or malignant diagnosis among patients with Birad 4 breast lesions
Authors: Laurent I. , Balleyguier C. , Rouzier R. , André F. , Marsiglia H. , Spielmann M. , Vielh P. , Delaloge S.
Published: March 2020

10578

Background: Preoperative cytological or histological diagnosis of breast lesions is mandatory in order to avoid unnecessary surgical biopsies, but on the other side preoperative work-up may dangerously delay specific care of breast cancer. Solid lesions or microcalcifications (M) scored as Birad 4 are increasingly prevalent in western countries. A highly variable proportion of these lesions (20–80%) are breast cancer. Tools to help clinicians recognize cancers and preneoplastic lesions among true benign conditions may be very helpful in clinical practice. Methods: Radiological, clinical and pathological data of consecutive patients with Birad 4 breast M (N = 384 biopsies among 354 patients) or nodular lesions (N = 172 FNAC among 167 patients) seen in a multidisciplinary breast clinic were prospectively recorded. A multivariate analysis of factors predicting for a final cancer or pre-malignant diagnosis was performed and two nomograms were constructed using the R statistical package for both nodular lesions and M. They were validated by bootstrapping. Variables tested included age, size and palpability of lesion, Gail score, menopausal status, HRT use, progression of lesion (M), and presence of associated symptoms. Results: Median age was 57 years (18–92) for the entire population. Patients with nodular lesions were menopausal in 64.5%, median size of their lesion was 12 mm (4–50), 32% were palpable; 43% had a final diagnosis of breast cancer and 3.5% of atypical hyperplasia or LCIS. 69% of patients with M were menopausal, 31.25% had a final diagnosis of breast cancer and 9.8% of atypical hyperplasia or LCIS. Among patients with nodular lesions, age and palpability were the sole independent predictors of cancer or precancerous lesions (p = 0.04 and 0.004), but the other variables (Gail, menopause, HRT) added discrimination with a concordance index of 0.71. Among patients with M, the only independent predictive variable was the recent progression of the lesions (p = 0.01). The nomogram had a concordance index of 0.69. Conclusion: Our study provides two original nomograms for the prediction of the pre-malignant or malignant nature of recently discovered solid breast lesions and M. Gail model alone is not a highly useful tool in daily individual cancer prediction.

No significant financial relationships to disclose.
Hepatic intra-arterial chemotherapy in patients with metastatic breast cancer
Authors: Fazio N. , Medici M. , Colleoni M. , Rocca A. , Torrisi R. , Orsi F. , Della Vigna P. , Bonomo G. , Monfardini L. , Goldhirsch A.
Published: March 2020

10581

Background: Hepatic intra-arterial chemotherapy has been reported to produce higher response rate than systemic in patients (pts) with metastatic colorectal cancer. In breast cancer the liver is involved in up to 60% of cases and often conditions the prognosis. Nevertheless, only rare hepatic arterial infusion studies were published. Therefore, based on our previous experience in hepatic metastatic colorectal malignancies, we evaluated efficacy and toxicity of hepatic intra-arterial chemotherapy in pts with metastatic breast cancer. Methods: A three-day continuous arterial infusion (CAI) of fluorouracil 1000 mg/m2 q 24 hrs, with cisplatin 10 mg/m2 twice daily, and mitomycin-c 1 mg/m2 twice daily, was performed through a percutaneous radiological temporary trans-subclavicular catheter. Pts with responsive disease received up to four cycles every six weeks. Pts still responding could carry on with cisplatin and fluorouracil, without mitomycin-c. Pts were hospitalized and the catheter was removed upon end of infusion. Results: From 9.2000 to 6.2005, 25 pts with progressive liver metastases from breast cancer were treated. Nine had more than 50% of liver involvement. Fifteen had also extra-hepatic metastases. All had received antracyclines and 22/25 taxanes. Pts had a median of five previous chemotherapy lines. Median time from diagnosis of liver metastases to first CAI was 33 months (range: 7–110). Sixty-four total courses were administered, with a median of 2 (range: 1–7) per pts. Epigastric pain was the main clinical toxicity (54%) and iatrogenic gastro-duodenal ulcer, the main complication (28%). No relevant catheter-related complications occurred. Fifteen partial responses (60%) and eight stable diseases (32%) were observed. Response duration was 5.4 months (range: 2 - 27), time to progression 5.1 months (range: 2.5–29+), and median overall survival 13 months (range: 3.5+–32+). Conclusions: Hepatic arterial infusion of chemotherapy in heavily pre-treated pts with metastatic breast cancer is feasible and effective. A specific evaluation of quality of life should be performed to verify a real clinical benefit. An earlier timing during course of liver disease, and a shift to radiological implanted arterial port (allowing out-patient treatment), will be investigated.

No significant financial relationships to disclose.
Manageable safety profile in patients with taxane-resistant metastatic breast cancer (MBC) treated with ixabepilone: Final report
Authors: Fornier M. N. , Martin M. , Klimovsky J. , Bunnell C. A.
Published: March 2020

10587

Background: The epothilones, a new class of antineoplastic agents, promote tumor cell death by stabilizing microtubules and inducing apoptosis. Ixabepilone was selected from over 300 epothilone analogs due to its high in vivo efficacy, good metabolic stability and low protein binding. Methods: This international, multicenter, open-label Phase II trial was designed to assess the activity of ixabepilone in patients (pts) with highly resistant MBC who had progressed following taxane treatment. Eligible pts were aged ≥18 years with MBC (progressed on or within 4 months of taxane therapy [or within 6 months if adjuvant taxane only]). Pts were excluded if they had had ≥3 prior chemotherapy regimens for MBC or had ≥Grade 2 neuropathy. Ixabepilone (40 mg/m2 q3w) was administered as a 3-hour infusion for a maximum of 18 cycles, unless there was evidence of progressive disease and/or pts met discontinuation criteria. Toxicity was evaluated continuously. Results: Of 49 pts (median age 54 years, range 30–81), 86% of pts had received ≥2 prior chemotherapy regimens. Treatment-related adverse events (TRAEs) were manageable and mostly Grade 1 or 2 (45%). Treatment-related neuropathy was mostly sensory, mild-to-moderate, cumulative and reversible. Sensory neuropathy was managed mainly with dose reductions (12 out of 49 pts had their dose reduced due to neuropathy). Treatment-limiting or severe neuropathy generally resolved or lessened in intensity within 1–2 months after therapy discontinuation. Febrile neutropenia was reported in only 2 pts, in addition, 2 pts (4%) developed treatment-related infection with neutropenia. Only six pts (12%) required growth factor support for neutropenia during their treatment. Progressive disease was the most common reason for discontinuing the study (36%), with 16% discontinuing due to TRAEs. Conclusions: Ixabepilone demonstrates an acceptable safety profile, along with promising antitumor activity, in pts with clearly defined taxane-resistant MBC.

[Table: see text]

[Table: see text]
Docetaxel (Do) and liposomal pegylated doxorubicin in metastatic breast cancer (MBC) patients (pts): The French GINECO group experience
Authors: Guastalla J. P. , Largillier R. , Geay J. F. , Hardy-Bessard A. C. , Kirsher S. , Slama B. , Cretin J. , Orfeuvre H. , Goubely Y. , Pujade-Lauraine E.
Published: March 2020

10589

Background: Taxanes and anthracyclins are among the most effective agents in MBC. Ca has a favourable cardiac toxicity profile and we tested Ca in combination with Do. Methods: Two successive Ca-Do regimens (Reg) were evaluated in first line MBC pts with performance status ≤ 2, and good organ function including normal MUGA scan. Reg A (n = 53 pts): Ca 35 mg/m2/d1 q4wks + Do 40 mg/m2/d1 q2wks according to previous phase I study results (Guastalla JP et al, Proc Am Soc Clin Onc 2004) and Reg B (n = 14 pts): Ca 30 mg/m2/d1 + Do 75 mg/m2/d2 every 3wks (Alexopoulos A et al, Ann Oncol 2004). Pyridoxine (250 mg/d) was given continuously during treatment (Tt). Results: The 67 pts had a median age of 58 yrs (range 37–77 yrs); others characteristics (%): ER+ (75), PR+ (51), HER2+ (9), adjuvant anthracyclin (54) and hormonotherapy (60), visceral disease (78). Both regimens induced unbearable toxicities (Tox) leading to premature stopping of the trial. Dose reduction, Tt delay and early stopping due to Tox were noted (% pts) in A:68, 36, 48 and B:57, 64, 54. Mucositis-skin Tox was the most severe Tox (% Gr2/3; A:40/15, B:43/21) and was observed in 21 and 40% of pts at cycle 2 and 4. Hematotoxicity was worse in reg B: Gr3/4 neutropenia (A:28/9, B:14/57), anemia (A:0/0, B:7/7) and thrombopenia (A:0/0, B:14/0), febrile neutropenia (A:6, B:14), Gr2–3 infection (A:13, B:28). Others Gr2–3 toxicities (> 10%) included alopecia (A:64, B:78), fatigue (A:54, B:57), nausea/vomiting (A:19, B:50). Three pts had a reduction of LVEF without clinical cardiac toxicity Conclusions: The combination of Do and Ca according to the 2 schedules tested in this study induced an unexpected high rate of mucositis and skin toxicity.

No significant financial relationships to disclose.
Clinical significance of brain metastases occurrence in HER2 overexpressing metastatic breast cancer patients treated with trastuzumab
Authors: Mari V. , Chamorey E. , Italiano A. , Van Den Bos F. , Ferri-Dessens R. , Ferrero J. , Largillier R. , Ettore F. , Courdi A. , Paquis P. , Frenay M.
Published: March 2020

10593

Background: Recent data report that HER2 overexpressing metastatic breast cancer patients (HER+ MBC pts) treated with trastuzumab (T) have a high rate of Brain metastasis (BM). This study aimed to evaluate the prognostic significance of BM occurrence and the related clinical outcome in a specific patient population. Methods: All the HER+MBC patients treated with trastuzumab (with or without chemotherapy) between 09/1999 and 12/2004 were included in this study. Results: A total of forty three patients were enrolled into the study cohort. The median follow-up was 48 months (range, 11–166). Fifteen patients (35%) developped BM. The median interval from the the first MBC event to BM was 18 months (range, 1–65). In multivariate analysis; younger age was the only factor associated with BM occurrence (46 versus 57 years; p = 0.01). Patients with BM tend to have a longer median duration of response to T than patients without BM (16 months versus 13 months; p = 0.1). At the time of BM appearance, 6 of the 15 patients (40%) were still responding or had achieved extracranial stable disease while receiving trastuzumab. Twelve out of 15 (80%) pts received a whole-brain radiation therapy, and 8 pts continued to receive trastuzumab until extracranial disease progression. The median overall survival for patients diagnosed with BM was 10 months (range, 2–42). At three-year, there was no significant difference in overall survival rates between the two groups. The 3-YS was 63.5% and 66.7% for pts with or without BM, respectively; (p = 0.7). Conclusions: The BM occurrence in HER2+ MBC pts treated with Trastuzumab is not linked to tumour resistance, but likely related to the T inability to cross the blood-brain barrier. There is no impaired survival for these pts treated with effective and appropriate therapy.

[Table: see text]
Hormone replacement therapy (HRT) in women with previously treated primary breast cancer: Update XII
Authors: Bluming A. Z.
Published: March 2020

10596

Background: To assess the incidence of contralateral or recurrent breast cancer among women prospectively treated with HRT after initial breast cancer diagnosis. Methods: A community-based, prospective, single-arm, pilot study of HRT among 241 women with previously treated primary breast cancer. Results: Median duration of HRT is 83+ months (range 12+–161+). Median interval from initial surgery to initiation of HRT is 52 months (range 2–361 months). Follow-up to date is 100%. Actuarial disease-free survival (DFS), disease-specific survival (DSS), & median duration of HRT by stage are listed in the table. One hundred and fourteen patients have stopped HRT (47%), 57 because of anxiety about taking HRT (24%), 48 because of breast cancer development (20%), 3 because of the development of non-breast cancers, 2 died of nonmalignant disease, 3 because of HRT-associated symptoms, and 1 because of pulmonary emboli without clinical phlebitis. CHRT, as opposed to ERT, was administered to 50% of all patients and 57% of the 48 who subsequently developed breast cancer on study. Actuarial DFS to 20 years for T1N0 patients was 72% versus 63% for comparable T1N0 patients who did not receive HRT. Conclusions: No evidence to date of increased development, recurrence or of breast cancer-related death associated with post diagnosis HRT.

[Table: see text]

No significant financial relationships to disclose.
An evaluation of changes in biological markers (ER, PgR, or Ki67) after neoadjuvant chemotherapy (ET: epirubicin and docetaxel) in operable breast cancer
Authors: Tashima R. , Nishimura R.
Published: March 2020

10613

Background: Neoadjuvant chemotherapy (NAC) is a valid option not only for advanced breast cancer but also for operable breast cancer. It was reported that disease-free and overall survival after NAC were equivalent to those after adjuvant therapy. The role of biological markers for the prediction of NAC may be evaluated using pathological responsiveness. In this study, we investigated the changes in biological markers such as estrogen receptor (ER), progesterone receptor (PgR), or Ki67 after NAC. Methods: Eligible patients (pts) were newly diagnosed with large primary tumors > 3 cm or positive nodes. Fifty-two pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. In 51 cases out of the pts, pre-treatment needle biopsies and surgical specimen were analyzed for expression of ER, PgR, Her-2/neu, p53 and Ki67 by immunohistochemistry, and these data were compared to the pathological response. The pathological response was evaluated using the criteria of Japan Breast Cancer Society. Results: The median age was 47 (range, 29–67) and the mean tumor size was 5.2cm (range, 1.5–14.5). The clinical response was 86%; the BCS rate was 73% and pathological response was 31% including 3 cases with pCR. Regarding changes in biology after NAC, an average rate of ER positive cells significantly fell in 37% from 47% and that of PgR positive cells also fell in 14% from 32%. Most of cases, whose tumors were changed to ER/PgR negative from ER/PgR positive, were premenopausal women accompanied with amenorrhea during the treatment. Patients with lower ER, PgR, or a higher proliferation had a significantly greater benefit from NAC. The overexpression of Her2 was not correlated to pathological response, while p53 staining had a predictive value. And patients with positive nodes had a significantly favorable disease-free survival. Conclusions: The clinical effect of NAC (ET regimen) and the BCS rate by NAC were high. Although the rates of ER and PgR positive cells and proliferation were significantly reduced by NAC, a lower ER, PgR, or a higher proliferation might reflect a good pathological response. A negative change of ER or PgR by NAC might correlate with amenorrhea in premenopausal pts.

No significant financial relationships to disclose.
Correlation between vascular endothelial growth factor and c-met expressions in breast carcinoma
Authors: Matkowski R. , Gisterek I. , Suder E. , Lacko A. , Szelachowska J. , Ramsey D. , Kornafel J.
Published: March 2020

10621

Background: Vascular endothelial growth factor (VEGF) is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis. This cytokine selectively induces cells proliferation and migration, increases permeability of microvessels and activates proteolitic enzymes involved in tumor invasiveness. C-met is tyrosine kinase receptor; its activation can increase tumorigenicity, induce cell motility and enhance invasiveness and metastasis. This protein can increase production of protease and urokinase which are associated with membrane degradation crucial for metastasis. The relationships between both cytokines are not clearly identified. In this study, we evaluated VEGF and c-met expression in homogenous group of 99 patients with stage II ductal breast carcinomas and analyzed correlations between both markers. Methods: Microscopic studies were performed on formalin-fixed, paraffin-embedded cancer tissues, obtained during surgery and stained routinely with haematoxylin and eosin. Expression of VEGF and c-met was evaluated using a standard immunoperoxidase technique and area with molecule expression, intensity of color reaction and product of both findings were counted. Association between markers expressions was tested by Spearman Correlation Coefficient. Results: Expression of c-met was found in 37 (37.37%) breast tumors, while expression of VEGF was observed in 67 (67.67%) cases. There were strong correlations between expressions of both cytokines. The relationships were found between area with molecules’ expression (p = 0.0438) and intensity of reaction (p = 0.0461), also in the product of both findings (p = 0.0229). Conclusions: The results of our study confirms hypothesis that c-met may act as an indirect angiogenic factor by inducing expression of VEGF.

No significant financial relationships to disclose.
Toxicity and outcome data in a phase II study of weekly docetaxel in combination with erlotinib in recurrent and/or metastatic breast cancer (MBC)
Authors: Kaur H. , Silverman P. , Singh D. , Cooper B. W. , Fu P. , Krishnamurthi S. , Remick S. , Overmoyer B.
Published: March 2020

10623

Background: Single agent weekly docetaxel (D) is an active agent in the treatment of MBC with response rates of 29% - 53%. Erlotinib (OSI-774, Tarceva) is a tyrosine kinase inhibitor directed against the epidermal growth factor receptor (EGFR), and is overexpressed in 30–40% of breast cancers. EGFR inhibition by erlotinib (E) and its possible modulation of growth factor synthesis by breast cancer (BC) cells is an attractive treatment target. This study was designed to assess the combination of D and E in previously untreated recurrent &/or MBC. Methods: Adult patients (pts) with histologically confirmed BC without prior chemotherapy for recurrence or metastases were eligible. Treatment plan was: D [35 mg/m2 iv infusion weekly x 3 q4wks] and E 150 mg/d uninterrupted (D+E). E was to be continued in 4 week cycles after maximum tumor response or disease stabilization [following a minimum of 6 cycles of D+E]. The overall survival (OS) was estimated by Kaplan-Meier method. Results: 31of 40 planned female pts were enrolled between 12/02 and 9/05. Median age 52 years, range: 29–79. The median number of cycles of D +E received was 4, (range 1–9) and of E following D+E was 4 (range 1–29). The first 26 pts received planned D dose of 35mg/m2. Because of non-hematologic toxicity, trial was subsequently modified to start D at 30mg/m2.11/31 (36%) were not evaluable due to toxicity. Hematologic grade 3 or 4 toxicity was seen in 45% cases. Principal non-hematologic grade 3–4 toxicities included nausea, diarrhea, and constitutional symptoms seen in 30% of the pts. 4/9 pts receiving E after D+E experienced hematologic, hepatic, constitiutional, and eye (1 each) grade 3 toxicity only. Best clinical response in the 20 evaluable pts included; PR 11(55%), SD 7 (35%), PD 2 (10%). OS (n = 31) was 71% at 12mos, 42% at 24 mos with median OS 23 mos. Conclusions: Combination therapy of advanced breast cancer with Docetaxel and Erlotinib showed promising activity with favorable response compared to other studies. The combination is associated with moderate to severe hematological and non-hematological toxicities. Randomized trials are warranted to further investivate the efficacy of this combination compared to single agent Docetaxel. (Support: Sanofi-Aventis & Genentech.)

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Capecitabine plus docetaxel (XT): A first line, phase II clinical trial in metastatic breast cancer
Authors: Vogel C. L. , Tan-Chiu E. , Gokce F.
Published: March 2020

10624

Background: The XT combination originally published at (X) dosed at 1250 mg/m2 bid po x 14 days and (T) at 75 mg/m2 q3 weeks I.V. respectively yielded good response rates and an overall survival advantage compared with single agent docetaxel at 100 mg/m2. However, the toxicity profile of this regimen has led to major dose and schedule modifications by most oncologists. Methods/Results: We initiated a Phase II trial at doses of X at 900 mg/m2 bid po x 14 days and T at 36 mg/m2 d 1 and 8. Three responded and the mean no. of cycles for these patients was 3.8. Since four of 6 went off study because of toxicity two additional dose levels were studied in 6 patients each. A second cohort received X at 650 mg/m2 bid and T at 30 mg/m2. With 6 evaluable patients, four of 6 responded but all 4 required further dose reductions. Mean no. of cycles received was 4.2. A third cohort of 6 patients received X at 825 mg/m2 plus the lower T at 30mg/m2 who received a mean no. of cycles of 6. While only 1/6 responded 3 additional patients had stable disease with marked decreases in CEA or CA 15–3 suggestive of anti-tumor response. Only 1/6 required a dose reduction. Among the 18 patients, epiphora was described by 5 (28%). Only 3 patients developed significant leukopenia, and thrombocytopenia was not seen. T-induced nail changes were uncommon but were severe in one patient. Two patients at the first dose level, but only one at lower levels developed mucositis. Grade 1 anemia was common but managed easily with growth factor support. Conclusions: The response rate of 44% is encouraging with these lower doses of XT. We recommend further studies using X at 825 mg/m2 and T at 30mg/m2 since these doses were associated with encouraging response rate and a better toxicity profile than higher doses. Even at this higher dose of X dose reductions may well be needed. (Supported by a grant from Roche Laboratories, Inc.)

No significant financial relationships to disclose.
A clinical review of 33 cases of breast phyllodes tumor over the last 20 years
Authors: Lenhard M. S. , Kahlert S. , Himsl I. , Ditsch N. , Untch M. , Friese K. , Bauerfeind I.
Published: March 2020

10629

Background: The “Cystosarcoma phyllodes” of the breast is a rare entity which accounts for 0.5 % of all breast neoplasms. The diagnosis should be considered in all rapidly growing breast nodules. We reviewed all cases of this rare disease that presented at our hospital in the last 20 years. Methods: The data of 5270 patients with primary breast neoplasms treated in our department between 1984 and 2005 were retrospectively analyzed for the histopathologic diagnosis of a cystosarcoma phyllodes. Results: 33 patients with cystosarcoma phyllodes of the breast could be identified. The median age at diagnosis was 47 years. Median follow up was 86 months. The tumors were classified histologically into benign (40%), borderline (27%) and malignant tumors (33%) based on standardized criteria; 3 tumors were unclassified. Surgery was conducted as a breast conserving (58%) or radical operation (mastectomy) (42%). Median tumor size was 7.1 cm, and no lymph node infiltration was found in the 8 patients who received axillary lymph node dissection. Local recurrence occured in 8 patients (26%). 75% (6/8) of the patients with a local recurrence had been treated with a breast conserving surgery. In patients with the diagnosis of a malignant phyllodes tumor we observed a recurrence rate of 40% (4/10), in those with borderline tumors of 25% (2/8) whereas those with benign phylloides tumor had a local relapse rate of 8% (1/12). Distant metastases were seen in 4 patients (12%) with a malignant phyllodes tumor. All patients with distant metastases in the follow up had been treated radically at primary diagnosis. Neither regarding age at primary diagnosis nor in tumor size there was a significant difference between patients with local recurrence or metastasic spread and those without (p = 0.284 tumor size, p = 0.739 for age, Wilcoxon-W). Conclusions: We recommend local excision with appropiate surgical margins in all patients if the tumor-to-breast ratio is sufficient for good cosmesis. Based on our data, routine axillary lymph node dissection is not recommended. Patients with a malignant tumor are at higher risk for local recurrence and metastasic spread. Therefore, the histopathologic classification seems to be the strongest prognostic factor in this disease.

No significant financial relationships to disclose.