BRCA in breast cancer: from risk assessment to therapeutic prediction.
BRCA1/2 mutations are the most commonly identified germ line gene mutations in patients with hereditary breast cancer. These proteins have many critical cellular functions, including repair of DNA double-strand breaks. The role of defective BRCA1/2 as a predictor of response to DNA-damaging agents has been studied extensively in preclinical models, but prospective clinical validation is lacking. Poly [ADP-ribose] polymerase (PARP) inhibitors illustrate the concept of synthetic lethality in cells with defective BRCA1/2 and numerous PARP inhibitors are being evaluated in patients with BRCA1/2-associated tumors. BRCA1/2 mutation or functional loss will likely serve as a useful predictive biomarker of response to treatment with PARP inhibitors.
Diamond
Jennifer R
JR
Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, University of Colorado at Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Borges
Virginia F
VF
Eckhardt
S Gail
SG
Jimeno
Antonio
A
D000970:Antineoplastic Agents / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002986:Clinical Trials as Topic; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D009154:Mutation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012306:Risk; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000067856:Poly(ADP-ribose) Polymerase Inhibitors