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PARP Inhibitors for the Treatment and Prevention of Breast Cancer

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Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors, a novel class of drugs that target tumors with DNA repair defects, have received tremendous enthusiasm. Early preclinical studies identified BRCA1 and BRCA2 tumors to be highly sensitive to PARP inhibitors as a result of homologous recombination defect. Based on this premise, PARP inhibitors have been tested in early phase clinical trials as a single agent in BRCA1 or BRCA2 mutation carriers and in combination with chemotherapy in triple-negative breast cancer patients. For high-risk populations, use of PARP inhibition as a prevention agent has been postulated, but no robust preclinical or clinical studies exist yet. We review the preclinical and clinical studies in treatment of breast cancer and rationale for use of PARP inhibitors as a prevention agent for high-risk populations. Of significance, PARP inhibitors vary significantly in mechanism of action, dosing intervals, and toxicities, which are highlighted in this review.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Acknowledgment

James M. Ford is supported by research grants from the Breast Cancer Research Foundation and the Susan G. Komen for the Cure Foundation. Shaveta Vinayak is supported by research grants from the ASCO Cancer Foundation.

Disclosure

JMF has been a consultant for Lead Pharmaceuticals/BioMarin. He has received funding for a clinical trial from Sanofi-Aventis and an honorarium from the American Society for Clinical Oncology for an educational talk at the 2010 meeting.

SV reports no potential conflicts of interest.

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Authors and Affiliations

  1. Department of Medicine, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA, 94305-5151, USA

    Shaveta Vinayak & James M. Ford

  2. Department of Genetics, Stanford University School of Medicine, 269 Campus Drive, CCSR 1115, Stanford, CA, 94305-5151, USA

    James M. Ford

Authors
  1. Shaveta Vinayak
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  2. James M. Ford
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Correspondence to James M. Ford.

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Vinayak, S., Ford, J.M. PARP Inhibitors for the Treatment and Prevention of Breast Cancer. Curr Breast Cancer Rep 2, 190–197 (2010). https://doi.org/10.1007/s12609-010-0026-0

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