<b>Expert opinion</b>: The transition to multi-gene panels in breast cancer patients has improved the likelihood of capturing a rare variant in a well-established gene associated with hereditary breast cancer (e.g.<i>BRCA1 and BRCA2, TP53</i>).
Hereditary breast cancer is characterized by an inherited susceptibility to breast cancer on basis of an identified germline mutation in one allele of a high penetrance susceptibility gene (such as BRCA1, BRCA2, CHEK 2, TP53 or PTEN).
Familial breast cancer is associated with mutations in several genes (BRCA1, BRCA2, p53, ATM) whose protein products protect against radiation-induced genotoxicity.
Hereditary breast cancer syndrome was firstly associated with BRCA1 and BRCA2 genes the mutations of which confer high risk to develop breast and/or ovarian cancer.
Hereditary breast cancer has been associated with mutations in the BRCA1 and BRCA2 genes and has a natural history different from sporadic breast cancer.
A cohort of unrelated individuals with breast cancer due to the presence of either BRCA1 (121) or BRCA2 mutations (109) and individuals with familial breast cancer not due to BRCA1/2 mutations (722) were genotyped using Taqman SNP Genotyping Assays.
A polygenic model in which many individually weak genes combine multiplicately to cause a 50-fold range of risk in the population explains several puzzling aspects of familial breast cancer epidemiology, including the very high risk in some families and the failure to identify important new genes since the discovery of BRCA1 and BRCA2.
Although the BRCA1 and BRCA2 genes are the most common sites for hereditary breast cancer mutations, there are other hereditary gene mutations associated with breast cancer.
BC patients from 54 BRCA1 and BRCA2-negative families with elevated BC risk and 120 matched controls were considered for germline DNA whole exome sequencing.