Prospects and Challenges in Defining Risk-reducing Medications for the Prevention of BRCA1/2-associated Breast Cancer

BRCA1 and BRCA2 pathogenic variant carriers have a high lifetime risk of breast cancer. Risk-reducing bilateral mastectomy, the most established prevention method, is utilised by fewer than half BRCA1/2 carriers, despite being widely recommended by international guidelines. Currently available risk-reducing medications are limited to endocrine therapies that have limited evidence and minimal uptake. There is a pressing need for alternative strategies for carriers who wish to take action against their cancer risk, while balancing other health interests, including fertility. In this review, we explore the wide landscape of risk-reducing medications and methods that have been investigated specifically for BRCA1/2 carriers, with a focus on understanding the cells-of-origin, key determinants of tumor initiation, and signaling pathways implicated in BRCA1/2-related breast cancer, as well examining some of the practical challenges in translating this research into clinical trials.