title: Clinical management of hereditary breast cancer syndromes.
abstract: Over the past 15 years there has been substantial improvement in the understanding of hereditary breast cancer. Germline genetic testing for mutations in BRCA1, BRCA2, PTEN and TP53 allows for the identification of individuals at increased risk for breast, ovarian and other cancers. Advances in screening, prevention and treatment have led to improved clinical management which is best defined for BRCA1 and BRCA2 mutation carriers. The addition of screening techniques such as breast magnetic resonance imaging has been shown to lead to earlier detection. Risk-reducing salpingo-oophorectomy leads to a reduction in the risk of both ovarian cancer and breast cancer and also is associated with an improvement in overall survival. BRCA1/2 mutation status may be applicable to systemic therapy decisions. Preclinical and early clinical research suggests that specific classes of chemotherapy may be more effective in mutation carriers. Finally, PARP inhibitors represent a novel therapeutic strategy that exploits the weaknesses of BRCA1/2-associated malignancies.
authors.affiliation: Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Clark
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D016504:Breast Self-Examination; D055088:Early Detection of Cancer; D042241:Early Diagnosis; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008327:Mammography; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics / Q000628:therapy*