Genetics of Hereditary Breast Cancer

Abstract

The identification and clinical management of patients at inherited risk for breast cancer has become an integral part of the practice of preventative medicine and oncology. Although only about 5–10% of all cases of breast cancer are attributable to a highly penetrant cancer predisposition gene, individuals who carry a cancer susceptibility gene mutation have a significantly higher risk of developing breast cancer, as well as other cancers, over their lifetime compared to the general population. The ability to distinguish those individuals at high risk allows physicians and other health-care providers to intervene with appropriate counseling and education, surveillance, and prevention – with the overall goal of improved survival for these individuals. Recently, a number of germline alleles have been identified that have a modest impact on the risk of breast cancer [1] but there remain only a handful of genes in which a mutation substantially elevates the risk of breast cancer. These include BRCA1, BRCA2, TP53, PTEN, and CDH1. This chapter will provide an overview of the clinical features, cancer risks, causative genes, and medical management for the most clearly described hereditary breast cancer syndromes with particular attention to the most frequently encountered hereditary breast and ovarian cancer syndrome (HBOC) due to an underlying mutation in BRCA1 or BRCA2. The surgical management of HBOC will be discussed in Chap. 4.