10552 Background: The characteristic pathologic features of breast cancers in women with a BRCA1 mutation suggest that women with hereditary breast cancer might have a worse than expected prognosis, but the results of clinical studies have been inconsistent. The current study is a national population-based study of Israeli women aimed at evaluating the impact of the inheritance of a BRCA1 or a BRCA2 mutation on breast cancer prognosis. Methods: All incident cases of invasive breast cancer diagnosed in Israel from January 1, 1987 to December 31, 1988 were identified. Paraffin-embedded tumor blocks or unstained slides and pathology and oncology records were requested for all patients. DNA was extracted from each paraffin block and was analyzed for three founder Jewish mutations in BRCA1 and BRCA2. Of 2,514 diagnosed cases, a pathology sample was retrieved from 1,794 (71.4%) and the medical record was retrieved for 1,545 of these (86.1%). Results: A BRCA1 or BRCA2 mutation was identified in 10% of Ashkenazi women with breast cancer, including 18% of women diagnosed below the age of 50. The adjusted hazard ratio for breast cancer-specific survival was not different for non-carriers and carriers of a BRCA1 (HR = 0.8, 95% CI: 0.5 - 1.3, p = 0.3) or BRCA2 (HR = 1.3, 95% CI: 0.8 - 2.2, p = 0.3) mutation. Among women who were treated with CMF/CAF chemotherapy, BRCA1 carriers experienced better survival than non-carriers (HR = 0.5; 95% CI 0.2–1.2) but the difference did not reach statistical significance (p = 0.1). Tumor size (>2 cm) was a significant predictor of breast cancer specific mortality in non-carriers (HR = 2.8; 95%CI: 2.2 to 3.5) but not in BRCA1 carriers (HR = 1.1; 95% CI 0.5 to 2.8). ER status also did not play a significant predictive role in survival of carriers. Conclusions: Compared to non-carriers, women with breast cancer who carry a founder Jewish mutation in one of the BRCA genes experience similar or possibly even lower breast cancer-specific mortality rate, in spite of a bad profile of prognostic factors. No significant financial relationships to disclose.
Bisphosphonates are traditionally used for treatment of osteoporosis and more recently for treatment and prevention of bone metastases in various malignancies. The use of 2nd-generation oral bisphosphonates has been reported to reduce the risk of developing breast and colon cancer but their influence on cancer survival has not been studied. Methods Two large cohorts of consecutively diagnosed cases with breast or colorectal cancer were studied for the association between use of 2nd-generation oral bisphosphonates and cancer survival. Using computerized prescription records, sustained use of alendronate/risedronate was assessed in postmenopausal women with newly diagnosed breast (n = 2,843) or colorectal cancer (n = 1,706). Overall survival and cancer-specific survival were evaluated using time dependent analysis. Results Postmenopausal women with breast cancer previously unexposed to bisphosphonates who used 2nd-generation bisphosphonates after diagnosis for at least one year had a significantly better survival than non-users, adjusted for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.86, breast cancer-specific survival: HR = 0.26, 0.10-0.71, p = 0.009). A similar advantageous hazard ratio was found in users with ER positive, ER negative and HER2neu positive tumors. A similar significantly better survival was noted for colorectal cancer after adjustment for age, tumor stage and grade (Overall survival: HR = 0.53, 0.33-0.85, colorectal cancer-specific survival: HR = 0.44, 0.21-0.88, p = 0.02). Women who used bisphosphonates before diagnosis did not exhibit a significant survival benefit. Pharmacogenetic studies of F(D)PPS (Farnesyl Pyrophosphate Synthase), a gene coding a key step in the mevalonate pathway revealed direct correlation between a minor homozygous status and survival in bisphosphonate users. Conclusions The use of 2nd-generation bisphosphonates initiated after diagnosis was associated with a significant improvement in overall and in cancer-specific survival of postmenopausal women with breast or colon cancers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-03.
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