PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers
Oncology Department, CITOHL, Lyon-Sud Hospital, Cancer Institute of Hospices Civils de Lyon (IC-HCL), Hospices Civils de Lyon, 69495 Lyon, France
Lyon-Sud Medicine School, University of Lyon, University Claude Bernard Lyon 1, 69008 Lyon, France
Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, CNRS UMR 5558, Université Claude Bernard Lyon 1, 69100 Villeurbanne, France
Department of Pathology and Biopathology, Jean Perrin Comprehensive Cancer Center, UMR INSERM 1240, University Clermont Auvergne, 63011 Clermont-Ferrand, France
Department of Cancer Genetics, CHU Montpellier, UMR IRD 224-CNRS 5290, Université Montpellier, 34295 Montpellier, France
Centre de Recherches Écologiques et Évolutives sur le Cancer (CREEC), UMR 224 CNRS-5290, University of Montpellier, 34394 Montpellier, France
Biochemistry and Molecular Biology Department, Hopital Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 69008 Lyon, France
Author to whom correspondence should be addressed.
Academic Editor: Dik C. van Gent
Received: 15 December 2021
Revised: 13 January 2022
Accepted: 21 January 2022
Published: 25 January 2022
OlympiAD and EMBRACA trials demonstrated the efficacy of PARPi, compared to chemotherapy, in patients with HER2-negative metastatic breast cancers (mBC) carrying a germline BRCA mutation. Patients with ER+/HER2-BRCA-mutated mBC seemed to have a higher risk of early disease progression while on CDK4/6 inhibitors and benefit from PARPi, especially when prescribed before chemotherapy. Importantly, the frequency of BRCA pathogenic variant (PV) carriers among ER+/HER2- breast cancer patients has been underestimated, and 50% of all BRCA1/2 mutated breast cancers are actually of ER+/HER2- subtype. Recent studies also highlight the benefit of PARPi in BRCA wild type mBC with HRD representing up to 20% of ER+/HER2- breast cancers. The OLYMPIA trial also demonstrated PARPi utility in patients with ER+/HER2- early breast cancers with BRCA PV at high risk of relapse. Consequently, implementation of early genotyping and new strategies for identifying patients with high-risk ER+/HER2- HRD breast cancers likely to benefit from PARPi is of high importance.