Functions of Breast Cancer Predisposition Genes: Implications for Clinical Management

Approximately 5-10% of all breast cancer (BC) cases are caused by germline pathogenic variants (GPVs) in various cancer predisposition genes (CPGs). The most common contributors to hereditary BC are BRCA1 and BRCA2, which are associated with hereditary breast and ovarian cancer (HBOC). ATM, BARD1, CHEK2, PALB2, RAD51C, and RAD51D have also been recognized as CPGs with a high to moderate risk of BC. Primary and secondary cancer prevention strategies have been established for HBOC patients; however, optimal preventive strategies for most hereditary BCs have not yet been established. Most BC-associated CPGs participate in DNA damage repair pathways and cell cycle checkpoint mechanisms, and function jointly in such cascades; therefore, a fundamental understanding of the disease drivers in such cascades can facilitate the accurate estimation of the genetic risk of developing BC and the selection of appropriate preventive and therapeutic strategies to manage hereditary BCs. Herein, we review the functions of key BC-associated CPGs and strategies for the clinical management in individuals harboring the GPVs of such genes.

Automated summary

Approximately 5-10% of breast cancer cases are caused by germline pathogenic variants in cancer predisposition genes. BRCA1 and BRCA2 are the most common genes associated with hereditary breast cancer. Other genes such as ATM, BARD1, CHEK2, PALB2, RAD51C, and RAD51D have also been identified as having moderate to high risk of breast cancer. The optimal preventive strategies for most hereditary breast cancers are still undetermined. Understanding the functions of breast cancer-associated genes can help estimate genetic risk and guide preventive and therapeutic strategies.