BRCA1/2 testing: therapeutic implications for breast cancer management

Br J Cancer. 2018 Jul;119(2):141-152. doi: 10.1038/s41416-018-0127-5. Epub 2018 Jun 5.

Abstract

Testing for germline BRCA1/2 mutations has an established predictive role in breast cancer risk assessment. More recently, studies have also identified BRCA1/2 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. BRCA1/2 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 BRCA1/2-mutated breast cancer, which led to the recent approval of olaparib, the first PARPi to be approved in breast cancer. Determining BRCA1/2 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • DNA Repair / genetics
  • Female
  • Germ-Line Mutation / genetics
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Phthalazines / adverse effects
  • Phthalazines / therapeutic use
  • Piperazines / adverse effects
  • Piperazines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / adverse effects
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases / genetics
  • Progression-Free Survival

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases
  • olaparib