Outcomes in BRCA mutation carriers: evaluation of current data for optimal clinical care

BRCA1 and BRCA2 are genes responsible for homologous recombination and repair of double-strand DNA breaks (1). Mutations in either gene increase the risk of malignancy and are responsible for the hereditary breast and ovarian cancer syndrome (HBOC). The lifetime incidence of breast cancer in those harboring BRCA1 or BRCA2 mutations has been estimated to be greater than 80% (2,3). The biology of BRCA1/2 mutation associated cancers is unique. BRCA1 mutated tumors in particular are often estrogen receptor (ER) and HER2 negative and express a phenotype of a basal-type breast cancer (4). They are typically highergrade tumors, with more metastatic potential and poorer outcomes (5). There has also been interest in the potential susceptibility of BRCA-mutated cancers to therapeutic agents, such as platinum-derived chemotherapy and PARP inhibitors, that take advantage of the defect in homologous DNA repair, so-called “synthetic lethality” (6).