bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superior survival of breast cancer BRCA1 /2 mutation carriers harboringG/G at the -309 position at the MDM2 promoter compared to those harboring T/T or G/T at this SNP
Authors: Nechushtan H. , Hamburger T. , Mendelson S. , Kadouri L. , Sharon N. , Pikarsky E. , Peretz T. 
Published: March 2020

10600 Background: A germ line single polymorphism in the promoter of the gene encoding the important modulator of P53, MDM2 has been described. The findings of G/G nucleotides at this position in contrast to G/Tor T/T were demonstrated to increase MDM2 transcriptional levels and were correlated with younger onset of cancers in patients with the Li-Fraumeni syndrome. Furhtermore gastric cancer patients harboring T/T at this position and treated with chemotherapy were found to have decresed survival compared to the other SNP carriers. P53 mutations appear in high frequency in tumors associated with BRCA1/2 mutations. Indeed it has been suggested that mutations in the p53 gene are a necessary step in tumorigenesis in BRCA tumors. Methods: Here we investigate the effect of the MDM2 SNP309 on overall survival and age of onset in breast cancer patients. MDM2 SNP309 was evaluated in Breast cancer Ashkenazy patients analyzed for the three common mutations in BRCA1/2- 180 patients who are positive for either of these mutation and 272 negative ones. 194 negative, Disease onset age and survival were analyzed for the different subgroups Results: Around a quarter of the whole population analyzed were identified as carriers of G/G at the -309 MDM2. There was no correlation between age of disease onset in either BRCA1/2mutation carriers and the specific genotype. In the BRCA1/2 mutation carriers we found a survival advantage in patients harboring the SNP309 G/G genotype(p-0.001 log rank test). Such an effect was not demonstrated in patients tested negative for the known Ashkenazy mutations Conclusions: In specific subgroups of breast cancer patients SNP309 G/G is associated with improved patient survival. A possible explanation for this finding could be the presence of a P53 which can be reactivated in the MDM2 SNP309 G/G carriers. No significant financial relationships to disclose.
Fulvestrant in the treatment of HER2-positive advanced breast cancer (ABC)
Authors: Robertson J. F. , Steger G. G. , Neven P. , Barni S. 
Published: March 2020

1061 Background: Patients with HER2-positive (HER2+) disease are regarded as less responsive to endocrine therapy, although there are data to suggest activity in some patients. Fulvestrant is a novel estrogen receptor (ER) antagonist with no agonist effects, and is licensed for the treatment of postmenopausal women with ABC after progression on prior endocrine therapy. Here we pool clinical experience data from HER2+ patients who received fulvestrant. Methods: Postmenopausal women with HER2+ disease were treated with fulvestrant 250 mg/month IM until progression/other reason for discontinuation. Clinical response was assessed monthly using RECIST or UICC criteria, or the clinical judgment of the physician. Clinical benefit (CB) was defined as the proportion of patients experiencing a response (complete or partial response [PR]) or stable disease (SD) lasting =6 months. Results: Fifty-three patients with HER2+ ABC and a median age of 61 years (range 30–85 years) received fulvestrant. Patients received a median of two prior endocrine therapies (range 0–3) and one chemotherapy (range 0–5) for ABC. ER and/or progesterone receptor (PgR) status was assessed in 52 patients. Twenty-two patients experienced CB (4 PR and 18 SD =6 months) with fulvestrant, giving a CB rate of 41.5% (n=53), with activity observed up to 4th-line endocrine therapy. CB rate was 47.8% amongst ER+/PgR+ patients (n=23) and 45.0% amongst ER+/PgR- patients (n=20). Sixteen adverse events (AEs) were reported (30.2%), with one considered severe (restlessness). No patients discontinued due to AEs. Conclusions: From these data, fulvestrant appears to demonstrate activity in patients with HER2+ ABC. Observed activity was independent of PgR status and is consistent with fulvestrant efficacy demonstrated in the overall ABC population. These are encouraging data, warranting further exploration of the use of fulvestrant in HER2+ disease. No significant financial relationships to disclose.
Clodronate compared to ibandronate breast cancer bone metastases patient preference study
Authors: Jagdev S. , Berry H. , Newsham A. , Smith A. , Flanagan L. , Perren T. , Dodwell D. , Velikova G. 
Published: March 2020

1068 Background: The use of bisphosphonates for patients with breast cancer bone metastases confers significant benefits. Prolonged IV bisphosphonate use burdens both patients and services and oral clodronate is often used. Ibandronate is a potent oral third generation bisphosphonate which is effective and well tolerated in patients with metastastic breast cancer. In Phase III studies, the incidence of adverse events for oral ibandronate was similar to placebo. Clodronate requires prolonged fasting and size of tablets and gastric irritation may be problematic, therefore ibandronate may provide advantages. The aim of this study was to investigate patients’ preferences between oral ibandronate and oral clodronate and to assess the reasons for preference. Methods: This randomised, open-label, cross-over study recruited 46 women with breast cancer bone metastases who were starting or established on IV bisphosphonates. Patients were randomised to receive one drug for two months then crossed over to the second for two months. 23 patients received ibandronate then clodronate and 23 received clodronate first. Patients completed questionnaires on pain and symptoms at baseline, at crossover and on completion of the study. Patient preferences were assessed at the end of the study. Results: Data on 41 patients were available for preference assessment in this initial analysis. 5 patients discontinued the study. 26/41 patients preferred ibandronate (63.4%) and 14/41 preferred clodronate (34.5%) (c2=3.10, p=0.078). 1 patient did not state a preference. Significantly more patients receiving ibandronate first preferred ibandronate (13/18), compared with those receiving clodronate first expressing a preference for clodronate (10/23) (c2 =6.44, p= 0.011). Tablet size (p=0.001) and number (p<0.001) scored highly as reasons for preference for ibandronate. The following toxicities were reported on ibandronate and clodronate respectively: nausea (17%, 9.7%), indigestion (9.7%, 4.8%) and pain flare (7.3%, 4.8%). Conclusions: Significantly more patients preferred oral ibandronate compared with oral clodronate, with size and number of tablets being important reasons for preference. No significant financial relationships to disclose.
Dental care and tooth extraction as a risk factor for developing osteonecrosis of the jaw after long-term bisphosphonate therapy in patients with metastatic breast cancer
Authors: Spadaro P. , Pitini V. , Altavilla G. , Ingemi M. , Dottore G. 
Published: March 2020

1076 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment in patients (pts.)with Multiple Myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factor for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure. Methods: This is a retrospective review of our experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates, between January 2002 and December 2006. Presentation, age, dental status, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 100 pts. with bone metastasis secondary to breast cancer, median age 63 years, treated with bisphosphonates were reviewed. ONJ developed in 5 (5%) pts. Age did not impact occurrence of ONJ. All 5 patients developed ONJ after a minimum of 100mg of Zoledronic Acid and 2700mg of Pamidronate. All pts. had a history of previous tooth extraction and inadequate dental care. Three pts. were treated with debridement and antibiotics and their lesions healed. Two pts. ended up suffering from a chronically exposed bone. Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests a strong association between dental care, tooth extraction, and the development of ONJ. No significant financial relationships to disclose.
Gemcitabine and cisplatin in metastatic breast cancer
Authors: Moura G. L. , Pasquini R. , Frare A. , Vianna K. , Albini L. , Padilha S. 
Published: March 2020

1084 Background: Gemcitabine plus cisplatin have synergistic activity and have been tested in several schedules and doses in metastatic breast cancer. Our objectives were to assesss the efficacy and toxicity of gemcitabine and cisplatin in pretreated patients. Methods: Measurable disease and at least two prior anthracycline and /or taxane-containing regimen in either metastatic or adjuvant setting was required. Treatment consisted of gemcitabine 700mg/m(2) IV infusion over 30 min plus cisplatin 30mg(2) given on day1 and 8 every 3 weeks. Results: Seventy four patients with median age of 48 years (range 26- 73) were recruited. A median of six cycles of the study treatment was delivered. The overal response rate was 30% (95% confidence interval, 12–53%). Median time to progreesion was 30.6 weeks (95%CI, 12.6–44 weeks). Median survival was 73.2 weeks (95% CI, 47.1–93.2 weeks). Toxicities included grade 3 and 4 leukopenia in 27(36.4%), anemia in 19 (25.6%) and oral mucositis in 4 (5.4%). No grade 3 or 4 peripheral neurophaty, hepatic or renal dysfunction was observed. No treatment-related death ocurred. Conclusions: Gemcitabine plus cisplatin is a well tollerated and active treatment in heavily pretreated patients with metastatic breast cancer. No significant financial relationships to disclose.
Lipid lowering effect of fulvestrant in hormone-sensitive metastatic breast cancer patients
Authors: Camerini A. , Amoroso D. , Garrone O. , Vincenti M. , Tartarelli G. , Donati S. , Valsuani C. , Siclari O. , Mattiot V. Polla , Sgambato A. 
Published: March 2020

1085 Background: Fulvestrant (F) is a pure anti-estrogen agent available for the HT of post-menopausal ormone-sensitive advanced breast cancer (ABC). Aim of the study is to analyze the effect(s) of F treatment on lipid profile, endometrial mucosa and coagulation indices (CI). Methods: 24 pts (mean age 66.2 ± 9.5 yrs) with hormone-sensitive ABC were enrolled. All patients (data on 21 pts) received at least one previous HT course, with 90.5% receiving =2 HT courses. Last HT was exemestane in 13/21, letrozole in 5/21 and other in 3/21 with a median withdrawal time of 19 days (range 3–1,456). All pts but one received at least one previous CT regimen, with 60% receiving =2 CT regimens. Complete fasting lipid blood profile and CI were assessed before F administration, every 3 months and at discontinuation. Endometrial mucosa thickness was evaluated before F administration and at end-study time. All patients referred no significant dietary changes during treatment. Pts receiving statins were excluded. Results: pts received a median of 6 F injections (range 3–14). We observed SD in 10/21 pts and PD in 11/21 pts with a mean TTP of 6.2 ± 2.9 months. Total cholesterol (C) levels significantly decreased during F treatment (214.1 ± 48.7 vs 194.0 ± 41.0 mg/dl; p=0.0084) together with LDL-C (119.5 ± 40.7 vs 104.2 ± 30.4 mg/dl; p=0.0067). HDL-C (62.4 ± 17.8 vs 64.3 ± 19.5 mg/dl; p = ns) and triglycerides (152.4 ± 64.5 vs 148.2 ± 61.6 mg/dl; p=ns) did not show significant changes. Subgroup analysis demonstrated a reduction in both pts receiving = 6 (n=17) or >6 (n=11) injections (204.6 ± 45.3 vs 186.6 ± 41.2 mg/dl, p=0.014 and 219.5 ± 48.9 vs 203.9 ± 33.3 mg/dl, p=ns respectively). All CI and mean endometrial mucosa thickness value did not vary. Conclusions: We observed a clear lipid lowering effect of F in our study population. We suggest a possible effect of F on lipid metabolism. Lipid lowering effect of F it’s evident during the first six months of treatment lasting in pts continuing therapy. No significant financial relationships to disclose.
Efficacy of i.v. and oral ibandronate in bone metastases breast cancer patients and some clinical aspects of bisphosphonates studies: Clinical experience of one trial center
Authors: Lichinitser M. , Semenov N. N. 
Published: March 2020

1096 Background: Ibandronate is the only bisphosphonate that has both i.v. and oral formulation. Previously similar effectiveness of 6 mg i.v. and 50 mg oral Ibandronate compared with placebo in breast cancer metastatic bone disease was demonstrated. Methods: Due to similar inc/excl criteria in both (MF 4265 and MF4414–34) trials, we directly compare frequency of pathological fractures, hypercalcemia and osteolisys markers dynamics for patients, who received ibandronate 6 mg i.v. monthly or 50 mg per os daily (n=58) with placebo (n=53) during 2 years. Results: The frequency of pathological fractures (PF) and hypercalcemia (HC) is strongly depending on the efficacy of antitumor treatment: in periods of progression PF were 42%, in periods without progression only 6,8%, p<0.0001. Ibandronate decrease frequency of PF and HC, as acute bone pain and narcotics requirement in progression periods. Hypercalcemia was observed in progression periods only. Ibandronate effectively suppressed osteolysis in periods of disease progression: level of dPyr decreased by 3% and CTx by 60%, while in placebo group dPyr increased by 25% and CTx by 58%. Conclusions: Ibandronate is effective in periods of disease progression. Development of new clinical research methodology of bisphosphonate trials is thus actual. No significant financial relationships to disclose.
Dose-dense docetaxel, carboplatinum and trastuzumab (ddTCH) as neoadjuvant therapy for human epidermal receptor 2 (HER2) positive breast cancer
Authors: Han H. S. , Doliny P. , Blaya M. , Gluck S. , Slingerland J. , Silva O. , Welsh C. , Hurley J. 
Published: March 2020

11003 Background: Docetaxel, cisplatin, and trastuzumab given every 21 days in Her 2-postitive breast cancer demonstrates a pathologic complete response (pCR) rate of 23%. Decreasing the interval between doses of chemotherapy has lead to improvement in survival in the adjuvant setting. In one study dose dense chemotherapy improved response only in patients whose tumors overexpressed her-2. We conducted a phase II trial to evaluate the efficacy and safety of neoadjuvant dose-dense TCH for HER 2-positive breast cancer. Methods: Patients with T2–4 N0–3 M0 HER-2 positive (by FISH) breast cancers were eligible. Neoadjuvant therapy consisted of carboplatinum (AUC 6) Day 1,15,29,43, docetaxel (75mg/m2) Day 1,15,29, 43 and weekly trastuzumab for 10 weeks 4mg/kg Day 1 then 2mg/kg Day 8,15,22,29,36,43,50,57,64, Pegfilgastrim Day 2,16,30,44. The primary end point was the rate of pCR. Results: Twenty patients are evaluable for response. The median age was 51.5 years (range 29–73). Mean tumor size was 5.6 cm. Patients had stage IIA (30%), IIB (15%), IIIA (45%), IIIB (5%), and IIIC (5%). Estrogen receptors were positive in 36% of tumors. No grade 4 or 5 toxicity occurred. The most frequent toxicity was hand-foot syndrome (Grade I 15%, Grade II 10%, Grade III 15%). Neutropenia occurred in 5 patients (Grade II 10%, Grade III 15%) There were no episodes of febrile neutropenia or hospitalizations. Grade I cardiotoxicity was seen in 30%. The rate of pCR was 40% in the breast and 35% in both breast and axilla. 16/20 patients (80%) had pathologically negative lymph nodes. Conclusions: Changing the scheduling of TCH from every 21 days to every 14 days improves the pCR rate from 23 to 40%. The regimen was well tolerated. No significant financial relationships to disclose.
Evaluation of the tumor marker Ca27.29 for risk stratification and treatment monitoring in primary breast cancer
Authors: Genss E. M. , Rack B. , Sommer H. L. , Schrader I. , Lorenz R. , Tesch H. , Söling U. , Noeding S. , Beckmann M. W. , Lichtenegger W. 
Published: March 2020

11005 Background: Several trials have shown an earlier detection of metast. disease in breast cancer pts by the use of TU- markers. Whether this lead time advantage can be translated into improved outcome is discussed controversially. We prospectively evaluated the role of Ca27.29 in breast cancer pts at primary diagnosis and during adjuvant systemic treatment within the German SUCCESS-Trial (n=3658 pts planned). Methods: The SUCCESS-Trial compares sequential chemotherapy with FEC-Docetaxel(Doc) vs. FEC- DocGemcitabine, followed by zoledronate 2 vs. 5 years in primary high risk N0 and N+ breast cancer pts. Ca27.29 levels were assessed using the specific ST AIA-PACK Ca27.29 reagents directed against MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Cut-off levels for the assay was 24 U/ml. Results: We analyzed 1098 breast cancer pts prospectively before start and after completion of chemotherapy. 21% of pts (n=226; median 17U/ml; range 4–410) had tumor marker elevation = 24 U/ml before and 48% (n=524; median 23U/ml; range 4–198) after completion of chemotherapy. Ca27.29 levels before and after chemo correl. significantly (p<.001). Of those pts who presented with elevated values initially, 14% remained positive, while 84% had normal Ca27.29 after chemo. Those pts with initially negative blood sampling, returned with high Ca27.29 in 38% and normal values in 62% of cases. While Ca27.29 was well balanced between the two treatment arms at primary diagnosis with a rate of 10% with elevated Ca27.29 in each arm, significantly more pts showed high Ca27.29 with FEC-DocGemcitabine compared to FEC-Doc (27% vs. 21%, p<.001). Ca27.29 elevation did not correl. with most conventional prognostic factors such as tumor size (p=.23), histopath. grading (p=.98) or HR-status (p=.46). However, we found a significant correlation of Ca 27.29 with the presence of lymph node metastases (p=.01) and Her2/neu-over-expression of the primary tumor (p=.04). Conclusions: Measurement Ca27.29 in peripheral blood of primary breast cancer is feasible and reproducible. Whether it can be used for risk stratification leading to more tailored treatment approaches and for the monitoring of treatment efficacy in individual pts will show further follow-up of the SUCCESS-Study. No significant financial relationships to disclose.
A prospective study of the impact of the 21-gene recurrence score assay on treatment decisions in N-, ER+ early stage breast cancer patients
Authors: Ben-Baruch N. , Hammerman A. , Klang S. , Liebermann N. 
Published: March 2020

11008 Background: The Oncotype DX™ Recurrence Score (RS) assay predicts distant recurrence risk and benefit of chemotherapy (CT) in N-, ER+ breast cancer patients (pts). In February 2006, Clalit Health Services in Israel (CHS) was the first public health insurer to reimburse the assay outside the USA. Methods: CHS requires a pre-authorization form with data on biological parameters and specification of treatment (Rx) recommendation (1) before knowledge of RS and (2) the Rx planned according to each of 3 possible RS risk levels. For the first 200 reimbursed assays, we compared: (1) the Rx offered without RS knowledge, (2) the Rx the patient actually received after RS, and (3) the planned Rx stated on the form to be given according to the RS. Results: 200 pts. Median age: 57 yrs (34–81). RS: Low risk (RS<18), 37.5%; Intermediate (int) risk (RS 18–30), 44.5%; High risk (RS≥31), 18%. In 20 pts, Rx recommendations before RS were not specified. Before the RS, CT was offered in 106/180 (59%) and hormonal therapy (HT) in 74/180 (41%). In 71/180 pts (39%) the actual Rx changed from the recommendation before RS - CT to HT in 62 pts (low risk: 37, int risk: 21, high risk: 4) and HT to CT in 9 pts (int risk: 4, high risk: 5). Suggested therapy by RS was not specified in 19 pts. In 30/181 (17%) actual Rx differed from planned - CT to HT in 20 pts (int risk: 17, high risk: 3) and HT to CT in 10 pts (low risk: 4, int risk: 6). Conclusions: RS changed the treatment decision in a significant proportion of pts (39%), mostly from CT to HT. In 58% of pts originally offered CT, knowledge of RS changed the Rx to HT. 12% of pts originally offered HT were treated with CT. Rx decisions in intermediate RS are sometimes not obvious. In 26% of intermediate RS, final Rx differed from original plan; in these cases, patients’ preferences might have had a major impact on decision making. No significant financial relationships to disclose.
Sensitivity of surveillance mammography for contralateral breast cancers and ipsilateral recurrences in survivors under 50
Authors: Weinstock C. , Bigenwald R. , Narod S. , Sun P. , Hochman T. , Warner E. 
Published: March 2020

11009 Background: Annual mammography is currently the gold standard for surveillance of breast cancer survivors for both ipsilateral recurrence and contralateral new primaries. The risk of either of these events occurring has been found to be inversely proportional to age and is at least 1% per year if breast cancer was diagnosed before age 50. (Chen et al 1999) (Komoike et al 2006). However, the sensitivity of screening mammography is significantly lower in young women. We therefore sought to determine the effectiveness of surveillance mammography according to age of diagnosis using a prospective database. Methods: The Henrietta Banting Database prospectively follows all new cases of operable breast cancer diagnosed from 1987 - 2004 at Women’s College Hospital. From the 1992 women in the database, we selected all patients diagnosed before age 60 who subsequently developed non-metastatic contralateral cancers (n=71 ) or ipsilateral recurrences (n=11 ). Records were obtainable for 59 of these 82 patients. Results: Method of detection and stage of diagnosis are listed in table below for the 59 patients according to age of diagnosis of second cancers. Overall, mammography was less effective at detecting contralateral and recurrent breast cancers in younger women, detecting only 24% of these cancers in women under 50 compared to 74% in patients 50 and older (Chi-Square, p<0.001). In addition, 77% of patients under 50 whose second cancers were detected by methods other than mammography had negative surveillance mammograms in the 15 months prior to diagnosis. Conclusion: Since mammography detected only 24% of second primary breast cancers/ recurrences in survivors < age 50 and almost one third of all detected cancers were locally advanced, more sensitive imaging modalities such as breast MRI should be considered for surveillance of young survivors. [Table: see text] No significant financial relationships to disclose.