Implications of BRCA Germline Mutations on Breast Cancer Medical Treatment

Abstract

Detection of BRCA germline mutations (gBRCAm) impacts breast cancer medical treatment—according to differential sensitivity to cytotoxic chemotherapy and the activity of PARP inhibitors—and not only familial prevention. Guidelines for genetic testing—initially mainly based on familial history, age, and triple negative breast cancer (TNBC) subtype—currently are expanding in order to offer new therapeutic options. In the early setting, gBRCAm patients present a similar outcome as the non-carrier population with standard neoadjuvant chemotherapy, and the role of platinum chemotherapy is still a matter of debate. In metastatic setting, international guidelines recommend the use of platinum-based chemotherapy in gBRCAm patients and more broadly in TNBC patients. Olaparib and talazoparib monotherapy are approved in metastatic gBRCAm breast cancer. To date, it remains unclear how the combination of platinum-based regimen and PARP inhibitors should be sequenced.