Systemic therapy options in BRCA mutation-associated breast cancer

Abstract

BRCA mutation-associated breast cancers are characterized by deficient homologous recombination of DNA, and 80 % of BRCA1-associated breast cancers display the basal-like molecular subtype. Traditionally, BRCA carriers have received conventional systemic chemotherapy based on their baseline tumor characteristics, and it is generally accepted that after the appropriate treatment the prognosis of a mutation carrier is equivalent to that of a patient with sporadic breast cancer. However, with the growing understanding of the functions of BRCA1/2 proteins in homologous DNA repair, it is recognized that BRCA-associated breast cancer tumors may have distinct biochemical characteristics and thus require tailored treatment strategies. Tumors arising in patients with BRCA mutations were shown to be particularly sensitive to platinum compounds or inhibitors of poly(ADP-ribose) polymerase. In addition, BRCA1-mutation carriers seem to benefit from anthracycline-taxane-containing regimens as much as sporadic triple-negative breast cancers do. In this article, we review the functions of the BRCA1 and BRCA2 genes, and their differential chemosensitivity in both the preclinical and clinical settings. The optimal chemotherapy regimen for this subset of patients still remains to be determined.