Hereditary Breast Cancer Non-CDH1 Associated

Although breast cancer (BC) mainly arises as a sporadic tumor, between 7 and 10% of BC patients present a pathogenic variant (PV) of selected genes. This prevalence was calculated on high-risk populations and could be even higher in general population. Women with BC susceptibility or hereditary BC represent a special setting of patients who deserve a personalized approach to their screening and treatment pathways. PVs of BRCA1 and BRCA2 genes are implicated in 15% of all familial BCs. Additionally, increasing evidence is available on germline mutations in several other genes which are associated to inherited susceptibility to BC. These PVs have been stratified according to their penetrance, although guidelines are somewhat discordant on this classification. PVs in high-penetrance genes, i.e., BRCA, p53, PTEN, STK11, PALB2, CDH1, carry a threefold or more increased risk of BC compared to the general population, moderate-penetrance genes, i.e., CHEK2, BARD1, ATM, lead to a twofold to threefold risk, whilst low-penetrance genes, i.e., RAD51, BRIP1, NF1, are associated to a onefold to twofold risk of BC. The deep knowledge of hereditary BC-associated genes and the identification of PVs is crucial to provide the proper prevention strategy in carriers and a targeted therapy in BC patients.