Implications ofBRCA1andBRCA2status for cancer clinical study outcomes

Germline mutations of the BRCA1 and BRCA2 genes are associated with higher risk of breast, ovarian, prostate and pancreatic cancers. Initial conventional treatment is largely the same as for non-BRCA1/2-mutated cancers although there is increasing evidence in a variety of cancer types to suggest that BRCA1 or BRCA2 mutation or inactivation has a role in predicting response to DNA-damaging chemotherapy. The development of PARP inhibitors promises an exciting new therapy in germline BRCA1/2 mutated cancers that directly exploits the genetic mutation. Studies in both germline BRCA1/2 mutation carriers and in platinum-sensitive, high-grade, serous ovarian cancer have demonstrated impressive efficacy when given either as a single agent or maintenance treatment following platinum-based chemotherapy. Initial studies in pancreatic and prostate cancer also suggest significant efficacy. In breast cancer, although efficacy has been demonstrated, the optimal patient population remains to be defined.