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

Purpose: Data of in vitro and small retrospective studies suggest that breast cancer (BC) (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to chemotherapeutic agents causing double strand DNA breaks, while sensitivity to spindle poisons, such as paclitaxel and docetaxel, has been found to be decreased. Clinical data on the latter, however, are very scarce. In this study, we assessed the sensitivity to taxane chemotherapy for metastatic BRCA1/2-associated compared with sporadic breast cancer.Methods: From the family cancer clinic database, we retrieved 36 BRCA1 and 13 BRCA2-associated BC patients treated with taxane chemotherapy for metastatic disease before October 1, 2008, and with available data on follow-up and response assessment. Objective response (OR), and progression-free survival (PFS) after start of taxane chemotherapy were compared with those of 62 sporadic patients with comparable age at diagnosis and year of detection of metastatic BC. A t-test or chi-square test was used to test for differences in characteristics and response types, and Kaplan-Meier survival analysis to calculate PFS.Results: Taxane chemotherapy consisted of docetaxel (n= 76) or paclitaxel (n=21), while 10 (9%) patients received a taxane/trastuzumab regimen. It was given as first-line palliative therapy in 9 BRCA1, 1 BRCA2 and 22 sporadic patients; but mainly as second/third line treatment (BRCA1 n=27, BRCA2 n=12, sporadic patients n=40, respectively). As compared to sporadic patients, BRCA1-associated patients had a significantly lower OR rate (ORR) overall (22% vs 46%, p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2098.