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 reference BRCA1 and BRCA2 genes. As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1 and BRCA2 predisposition 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 include TP53 mutations in Li-Fraumeni syndrome, STK11 mutations in Peutz-Jeghers syndrome, and PTEN mutations 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 as CHEK2, ATM, PALB2, and BRIP1. This paper will summarize all current data on new findings in breast cancer susceptibility genes.

1. Introduction

Breast cancer is a disease in which breast cells become abnormal and multiply to form a malignant tumor. Breast cancer is the most common form of cancer and the second most common cause of death from a neoplastic disease affecting women. One in 8 women will develop breast cancer in her lifetime in the developed world. There are a number of recognized risk factors for breast cancer development including hormonal, reproductive, and menstrual history, age, lack of exercise, alcohol, radiation, benign breast disease, and obesity. Nevertheless, the key factor to breast cancer development is the early onset of disease. Individual risk increases proportionally with affected relatives with breast cancer and early age of onset . Although approximately 10%–30% of breast cancer cases are attributed to hereditary factors, only 5%–10% of breast cancer cases are identified with a strong inherited component, while only a small fraction of these cases (4%-5%) is explained by mutations in high penetrant genes transmitted in an autosomal dominant manner .

BRCA1 and BRCA2 genes are the most commonly mutated genes, but additional genes associated with hereditary breast cancer are emerging [8]. New advances in genomic technologies have led to parallel testing of multiple genes. Customized next generation sequencing panels are now providing the simultaneous analysis of breast cancer predisposition genes, from high- to intermediate-penetrant genes. Nonetheless, some of these genes have also been associated with increased risk of other cancers, such as ovarian, pancreatic, and colorectal cancer.