title: Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer.
abstract: Since the initial discovery that pathogenic germline alterations in BRCA 1/2 increase susceptibility to breast and ovarian cancer, many additional genes have now been discovered that also increase breast cancer risk. Given that several more genes have now been implicated in hereditary breast cancer syndromes, there is increased clinical use of multigene panel testing to evaluate patients with a suspected genetic predisposition to breast cancer. While this is most certainly a cost-effective approach, broader testing strategies have resulted in a higher likelihood of identifying moderate-penetrance genes, for which management guidelines regarding breast cancer risk reduction have not been firmly established. In addition, the testing of more genes has led to increased detection of variants of uncertain significance. We review the current knowledge regarding both high- and moderate-risk hereditary breast cancer syndromes, as well as additional genes implicated in hereditary breast cancer for which there is limited data. Furthermore, strategies for cancer risk reduction in mutation carriers as well as therapeutic implications for those patients who harbor pathogenic germline alterations are discussed.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
authors.forename: Erin F
authors.initials: EF
authors.lastname: Cobain
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI.
authors.forename: Kara J
authors.initials: KJ
authors.lastname: Milliron
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; Department of Epidemiology, University of Michigan School of Public Health , Ann Arbor, MI. Electronic address: smerajve@umich.edu.
authors.forename: Sofia D
authors.initials: SD
authors.lastname: Merajver
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D018890:Chemoprevention; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005817:Genetic Counseling; D020022:Genetic Predisposition to Disease; D006801:Humans; D040242:Risk Reduction Behavior; D013577:Syndrome
keywords: BRCA1/2; Genetic testing; Hereditary breast cancer; Panel testing; TP53; Variant of uncertain significance