Sensitivity to Taxane Chemotherapy for Metastatic Breast Cancer in BRCA1 and BRCA2 Mutation Carriers Compared to Sporadic Breast Cancer Patients.

Purpose: To assess physician recommendations about the use of tamoxifen in premenopausal BRCA1 and BRCA2 mutation carriers. Methods: We mailed surveys to a stratified random sample of 1,286 physicians selected from the San Antonio Breast Cancer Symposium mailing list. Eligible participants were physicians whose practice consisted of ≥ 10% breast cancer patients. Participants were asked to complete a three-part, 10-minute questionnaire. Demographics and responses to hypothetical patient vignettes were analyzed. Results: Of potentially eligible participants, 27% responded to the survey, and 260 participants were included in the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status in making recommendations about tamoxifen to breast cancer patients; however, in an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2 mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P < .0001). In newly diagnosed breast cancer patients, physicians were much more likely to recommend tamoxifen to an estrogen receptor (ER)–positive mutation carrier versus an ER-negative carrier (94% v 27%; P < .0001). When the mutation carrier was diagnosed 10 years ago, physicians were still much more likely to recommend tamoxifen if the tumor was ER-positive versus ER-negative (79% v 35%; P < .0001). Conclusion: Physicians’ recommendations about tamoxifen use in mutation carriers with a history of breast cancer seem to be heavily dependent on ER status. This finding suggests that among mutation carriers, physicians are influenced by adjuvant treatment guidelines more so than the potential role that tamoxifen might play in the reduction of risk for contralateral breast cancer.

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Sensitivity to First-Line Chemotherapy for Metastatic Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

Journal of Clinical Oncology ◽

10.1200/jco.2008.19.9067 ◽

2009 ◽

Vol 27 (23) ◽

pp. 3764-3771 ◽

Cited By ~ 69

Author(s):

Mieke Kriege ◽

Caroline Seynaeve ◽

Hanne Meijers-Heijboer ◽

J. Margriet Collee ◽

Marian B.E. Menke-Pluymers ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Patients ◽

Metastatic Disease ◽

Sporadic Breast Cancer ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

First Line ◽

Brca2 Protein ◽

Line Chemotherapy

Purpose Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients. Patients and Methods From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007. Objective response (OR), progression-free survival (PFS), and overall survival (OS) after start of first-line chemotherapy were compared with those of sporadic patients, matched for year of birth, age at diagnosis of primary breast cancer, and year of detection of metastatic disease. Results The chemotherapy regimens most frequently used were anthracycline-based (n = 147) and cyclophosphamide, methotrexate, and fluorouracil (CMF)/CMF like (n = 68). As compared to sporadic patients, BRCA2-associated patients had a significantly higher OR (89% v 50%; P = .001), a longer PFS (hazard ratio multivariate [HRmult] 0.64; P = .04) and a prolonged OS (HRmult, 0.53; P = .005) after start of first-line chemotherapy for metastatic breast cancer. For BRCA1-associated patients, a nonsignificant trend for an increased OR (66% v 50%; P = .07), and a longer PFS (HRmult, 0.79; P = .14) after first-line chemotherapy for metastatic breast cancer was observed, but not for OS. Conclusion BRCA2-associated breast cancer is more sensitive to standard first-line chemotherapy for metastatic breast cancer in comparison with sporadic breast cancer, especially to anthracyclines. For BRCA1-associated breast cancer no statistically significant higher sensitivity was observed.

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