Screening for familial cancer risk: Focus on breast cancer

A breast or an ovarian cancer occurring at a young age and/or in a family where other cases preexist suggests that those patients should be candidates for screening for mutations. Despite decades of medical research, less than 30% of cases with a suggestive personal and/or family history of hereditary breast cancer have an identified causative gene mutation. The vast majority of these cases are due to a mutation in one of the highly penetrant breast cancer genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11) and various guidelines direct the management of these patients. A minority of cases are due to mutations in moderate-penetrance genes (PALB2, ATM, BRIP1, and CHEK2). A small number of low-penetrance alleles have been identified using advanced genetic testing methods. While these may contribute to risk in a polygenic fashion, this is likely to be relevant to a minority of cases and their identification should not be considered routine practice. Mutation testing currently requires a high index of suspicion for a specific contributing etiology, but next-generation sequencing may improve the identification of such genes and the clinical management of these cases. Where no genetic susceptibility is identified, lifetime breast cancer risk can be calculated with standard tools. Breast cancer risk management then depends on the calculated lifetime risk. The psychological consequences of such screening for mutation carriers and non-carriers are discussed.