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.
Division of Medical Oncology, Department of Medicine, University of Colorado Cancer Center, University of Colorado at Denver Anschutz Medical Campus, Aurora, Colorado, USA.
Jennifer R
JR
Diamond
Virginia F
VF
Borges
S Gail
SG
Eckhardt
Antonio
A
Jimeno
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