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Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations

Abstract

The poly-(ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib, have recently been approved for use in patients with metastatic breast cancer (BC) and germline BRCA 1 or 2 mutations due to improved progression-free survival compared to chemotherapy. An increasing number of clinical trials are evaluating the role of PARP inhibitors (PARPi) in BC, alone and in combination with other therapies (including immunotherapy), as well as in earlier stages of the disease. This review describes the unique mechanism of action of these drugs and puts into clinical context the results of pivotal clinical trials. We also discuss the future development of PARPi in BC, their potential combination with other strategies, including chemotherapy and immune-checkpoint inhibitors, and the impact of these treatments in current genetic counselling.

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Correspondence to Miguel Martín.

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Yolanda Jerez has a consultant or advisory role at Novartis, Pfizer, Roche, and AstraZeneca and has received speaker honoraria from Roche, Novartis, and AstraZeneca and travel grants from Roche, Novartis, Pfizer, and Teva. Ivan Márquez-Rodas has a consultant or advisory role and travel grants from BMS, MSD, Novartis, Pierre Fabre, Roche, Regeneron, Sanofi, Amgen, Bioncotech, MERCK-serono, Incyte. Miguel Martín has received research grants from Roche, PUMA, and Novartis; consulting/advisory fees from AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, and Pfizer; and speakers’ honoraria from AstraZeneca, Amgen, Roche/Genentech, Novartis, Daiichi Sankyo, and Pfizer. Sara López-Tarruella has a consultant or advisory role at Celgene, Novartis, Pierre Fabre, Pfizer, Roche, Eisai, and Lilly and an AZ travel grant from Celgene, Pfizer, Roche, and MSD. Inmaculada Aparicio and Manuel Alva declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Jerez, Y., Márquez-Rodas, I., Aparicio, I. et al. Poly (ADP-ribose) Polymerase Inhibition in Patients with Breast Cancer and BRCA 1 and 2 Mutations. Drugs 80, 131–146 (2020). https://doi.org/10.1007/s40265-019-01235-5

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