Loss of BRCA1 Expression May Predict Shorter Time-to-progression in Metastatic Breast Cancer Patients Treated with Taxanes

Abstract

Background: Preclinical studies have indicated that BRCA1 functions differentially to modulate the chemosensitivity of cancer cells. Patients and Methods: To clarify these findings, BRCA1 expression in primary tumors was evaluated by immunohistochemistry in 50 patients with metastatic breast cancer. Results: BRCA1 expression was absent in 29 (58.0%) out of the 50 breast tumors tested. BRCA1-absent tumors were more frequently progesterone receptor-negative (p=0.019) than BRCA1-present tumors. Taxane-based chemotherapy was administered to 19 patients. Although BRCA1 expression did not relate to the clinical tumor response to taxane-based chemotherapy, time-to-progression (TTP) was significantly shorter in patients with BRCA1-absent tumors than in BRCA1-present tumors (mean±SD: 6.5±4.9 and 14.7±5.9 months, respectively; p=0.006). The Cox proportional hazard model revealed that BRCA1 absence was an independent predictor of progression (hazard ratio: 3.22; p=0.035). Conclusion: These results suggest that the absence of BRCA1 expression is an independent predictor of shorter TTP in advanced breast cancer patients treated with taxane-based chemotherapy.