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PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers

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Oncology Department, CITOHL, Lyon-Sud Hospital, Cancer Institute of Hospices Civils de Lyon (IC-HCL), Hospices Civils de Lyon, 69495 Lyon, France
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Lyon-Sud Medicine School, University of Lyon, University Claude Bernard Lyon 1, 69008 Lyon, France
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Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, CNRS UMR 5558, Université Claude Bernard Lyon 1, 69100 Villeurbanne, France
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Department of Pathology and Biopathology, Jean Perrin Comprehensive Cancer Center, UMR INSERM 1240, University Clermont Auvergne, 63011 Clermont-Ferrand, France
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Department of Cancer Genetics, CHU Montpellier, UMR IRD 224-CNRS 5290, Université Montpellier, 34295 Montpellier, France
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Centre de Recherches Écologiques et Évolutives sur le Cancer (CREEC), UMR 224 CNRS-5290, University of Montpellier, 34394 Montpellier, France
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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
Cancers 2022, 14(3), 599; https://doi.org/10.3390/cancers14030599
Received: 15 December 2021 / Revised: 13 January 2022 / Accepted: 21 January 2022 / Published: 25 January 2022
(This article belongs to the Section Cancer Therapy)
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.
Recently, OlympiAD and EMBRACA trials demonstrated the favorable efficacy/toxicity ratio of PARPi, compared to chemotherapy, in patients with HER2-negative metastatic breast cancers (mBC) carrying a germline BRCA mutation. PARPi have been largely adopted in triple-negative metastatic breast cancer, but their place has been less clearly defined in endocrine-receptor positive, HER2 negative (ER+/ HER2-) mBC. The present narrative review aims at addressing this question by identifying the patients that are more likely benefit from PARPi. Frequencies of BRCA pathogenic variant (PV) carriers among ER+/HER2- breast cancer patients have been underestimated, and many experts assume than 50% of all BRCA1/2 mutated breast cancers are of ER+/HER2- subtype. Patients with ER+/HER2- BRCA-mutated mBC seemed to have a higher risk of early disease progression while on CDK4/6 inhibitors and PARPi are effective especially when prescribed before exposure to chemotherapy. The OLYMPIA trial also highlighted the utility of PARPi in patients with early breast cancers at high risk of relapse and carrying PV of BRCA. PARPi might also be effective in patients with HRD diseases, representing up to 20% of ER+/HER2- breast cancers. Consequently, the future implementation of early genotyping strategies for identifying the patients with high-risk ER+/HER2- HRD breast cancers likely to benefit from PARPi is of high importance. View Full-Text
Keywords: breast neoplasms; homologous recombination; poly (ADP-ribose) polymerase inhibitors breast neoplasms; homologous recombination; poly (ADP-ribose) polymerase inhibitors
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MDPI and ACS Style

Collet, L.; Péron, J.; Penault-Llorca, F.; Pujol, P.; Lopez, J.; Freyer, G.; You, B. PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers. Cancers 2022, 14, 599. https://doi.org/10.3390/cancers14030599

AMA Style

Collet L, Péron J, Penault-Llorca F, Pujol P, Lopez J, Freyer G, You B. PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers. Cancers. 2022; 14(3):599. https://doi.org/10.3390/cancers14030599

Chicago/Turabian Style

Collet, Laetitia, Julien Péron, Frédérique Penault-Llorca, Pascal Pujol, Jonathan Lopez, Gilles Freyer, and Benoît You. 2022. "PARP Inhibitors: A Major Therapeutic Option in Endocrine-Receptor Positive Breast Cancers" Cancers 14, no. 3: 599. https://doi.org/10.3390/cancers14030599

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