Hereditary Breast Cancer: The Era of New Susceptibility Genes

Breast cancer is the most common malignancy among females. 5%–10% of breast cancer cases are hereditary and are caused by pathogenic mutations in the considered referenceBRCA1andBRCA2genes. As sequencing technologies evolve, more susceptible genes have been discovered andBRCA1andBRCA2predisposition seems to be only a part of the story. These new findings include rare germline mutations in other high penetrant genes, the most important of which includeTP53mutations in Li-Fraumeni syndrome,STK11mutations in Peutz-Jeghers syndrome, andPTENmutations in Cowden syndrome. Furthermore, more frequent, but less penetrant, mutations have been identified in families with breast cancer clustering, in moderate or low penetrant genes, such asCHEK2,ATM,PALB2,andBRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.