The Best Care and Treatment for Breast Cancer Patients with BRCA Mutation

Abstract

Abstract Breast cancer can be associated with mutations of genes involved in the DNA damage response (DDR). In a minority of patients, approximately 10% overall of newly diagnosed breast cancer, a germline mutation is found; this rate varies with the age of diagnosis and subtype of breast cancer. BRCA1 and BRCA2 are the most common genes and make up about 60% of the germline mutations in breast cancers in most series. Other germline mutations are also being associated with a susceptibility to developing breast cancer, including PALB2, ATM, RAD51, BARD1, BRIP1, TP53, and some CHEK mutations as well as other rare genes. Somatic mutations may be found in the tumour and may be a target for treatment but these are even less frequent and data on the efficacy of targeting these mutations is not well understood. Over the last few years there has been data emerging regarding the optimal treatment of BRCA associated cancers. As well as platinum-based agents, these cancers may be susceptible to treatment with targeted therapies such as PARP inhibitors. This session will begin with a short background to the different disease biology associated with DDR deficiency in breast cancer, followed by an in-depth discussion of the latest Phase III data for PARP inhibitors in HER2- metastatic breast cancer; the OlympiAD and EMBRACA trials. The screening of these mutations in breast cancer is an area of active discussion. The role of BRCA in early and late breast cancer as well as in estrogen receptor positive and estrogen negative cancers will be presented. .Future directions in this area will also be discussed as well as the areas where we do not yet have answers. Tutt A et al. Nat Med. 2018 May;24(5):628-637; Robson M et al. N Engl J Med. 2017 Aug 10;377(6):523-533; Litton J et al. N Engl J Med. 2018 Aug 23;379(8):753-763