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BRCA1/2 testing: therapeutic implications for breast cancer management

British journal of cancer, 2018-07, Vol.119 (2), p.141-152 [Peer Reviewed Journal]

2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. ;The Author(s) 2018 ;ISSN: 0007-0920 ;EISSN: 1532-1827 ;DOI: 10.1038/s41416-018-0127-5 ;PMID: 29867226

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  • Title:
    BRCA1/2 testing: therapeutic implications for breast cancer management
  • Author: Tung, Nadine M ; Garber, Judy E
  • Subjects: Adenosine diphosphate ; Anthracycline ; BRCA1 protein ; Breast cancer ; Cancer therapies ; Chemotherapy ; DNA repair ; Health risk assessment ; Health risks ; Homologous recombination ; Homologous recombination repair ; Homology ; Inhibitors ; Mutation ; Ovarian cancer ; Ovarian carcinoma ; Patients ; Platinum ; Poly(ADP-ribose) ; Poly(ADP-ribose) polymerase ; Review ; Ribose ; Risk assessment ; Salts ; Taxanes
  • Is Part Of: British journal of cancer, 2018-07, Vol.119 (2), p.141-152
  • Description: 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.
  • Publisher: England: Nature Publishing Group
  • Language: English
  • Identifier: ISSN: 0007-0920
    EISSN: 1532-1827
    DOI: 10.1038/s41416-018-0127-5
    PMID: 29867226
  • Source: Geneva Foundation Free Medical Journals at publisher websites
    PubMed Central
    ProQuest Central
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