BRCA1/2 testing: therapeutic implications for breast cancer management

• Published in: British journal of cancer 2018-07, Vol.119 (2), p.141-152
• Main Authors: Tung, Nadine M., Garber, Judy E.
• Format: Article
• Language: English
• Subjects: 692/53/2423; 692/699/67/1347; Adenosine diphosphate; Anthracycline; Biomedical and Life Sciences; Biomedicine; BRCA1 protein; Breast cancer; Cancer Research; Cancer therapies; Chemotherapy; DNA repair; Drug Resistance; Epidemiology; Health risk assessment; Health risks; Homologous recombination; Homologous recombination repair; Homology; Inhibitors; Molecular Medicine; Mutation; Oncology; Ovarian cancer; Patients; Platinum; Poly(ADP-ribose); Poly(ADP-ribose) polymerase; Review; Review Article; Ribose; Risk assessment; Salts; Taxanes
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/s41416-018-0127-5

Testing for germline BRCA 1/2 mutations has an established predictive role in breast cancer risk assessment. More recently, studies have also identified BRCA 1/2 status as clinically relevant in the selection of therapy for patients already diagnosed with breast cancer. Emerging breast and ovarian cancer research indicate that BRCA status predicts responsiveness to platinum-based chemotherapy, as well as to inhibitors of poly(ADP-ribose) polymerase (PARP), owing to the ability of these interventions to inhibit DNA repair pathways. BRCA 1/2 mutation testing thus has important and expanding roles in treatment planning for subsets of patients with breast cancer. Recent studies have demonstrated different activity of platinum salts in BRCA -mutated compared with non- BRCA -mutated breast cancer. Furthermore, phase II/III studies of single-agent PARP inhibitors (PARPi) have shown encouraging progression-free survival results in patients with BRCA 1/2-mutated breast cancer, which led to the recent approval of olaparib, the first PARPi to be approved in breast cancer. Determining BRCA 1/2 mutation status in this breast cancer subgroup could potentially expand treatment options beyond the current standard of taxane and anthracycline-based chemotherapy. Although attempts have been made to develop scoring systems that measure defects in homologous recombination repair pathways to predict response to platinum or PARPi, none have yet made it into clinical use. In this review, we summarise the recent and ongoing preclinical and clinical studies on the treatment of BRCA -associated breast cancer, and discuss efforts to identify other breast cancer patients who may be responsive to therapies effective in BRCA mutation carriers, including platinum-containing chemotherapy and PARPi.