title: Genetics of breast cancer: a topic in evolution.
abstract: A hereditary predisposition to breast cancer significantly influences screening and follow-up recommendations for high-risk women. However, in patients with a suggestive personal and/or family history, a specific predisposing gene is identified in <30% of cases. Up to 25% of hereditary cases are due to a mutation in one of the few identified rare, but highly penetrant genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11), which confer up to an 80% lifetime risk of breast cancer. An additional 2%-3% of cases are due to a mutation in a rare, moderate-penetrance gene (e.g. CHEK2, BRIP1, ATM, and PALB2), each associated with a twofold increase in risk. Prediction models suggest that there are unlikely to be additional yet to be identified high-penetrance genes. Investigation of common, low-penetrance alleles contributing to risk in a polygenic fashion has yielded a small number of suggestive single-nucleotide polymorphisms (SNPs), but the contributive risk of an individual SNP is quite small. Mutation testing is currently recommended for individual genes in the appropriate clinical setting where there is a high index of suspicion for a specific mutated gene or syndrome. Next-generation sequencing offers a new venue for risk assessment. At the present time, there are clear clinical guidelines for individuals with a mutation in a high-penetrance gene. Otherwise, standard models are used to predict an individual's lifetime risk by clinical and family history rather than genomic information.
authors.affiliation: Divison of Medical Oncology, University of Washington, Seattle Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, USA shiovitz@uw.edu.
authors.forename: S
authors.initials: S
authors.lastname: Shiovitz
authors.affiliation: Divison of Medical Oncology, University of Washington, Seattle Divisions of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, USA Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Korde
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
keywords: BRCA; breast cancer; family history; genetics; multiplex gene panels; screening