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Exploiting Homologous Recombination Deficiency in TNBC

  • Translational Research (TA King and EA Mittendorf, Section Editors)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Since the identification of the BRCA1 and BRCA2 genes over two decades ago, considerable progress has been made in elucidating the role of defective DNA repair in the pathogenesis of triple-negative breast cancer (TNBC). Here, we discuss the significance of recent advances in our understanding of homologous recombination (HR) deficiency, emerging HR deficiency biomarkers, and novel clinical approaches for exploiting HR deficiency in TNBC.

Recent Findings

Recent preclinical and clinical studies have implicated homologous recombination (HR) pathway defects as viable targets in TNBC. New treatment strategies have emerged to exploit defective HR pathways, including platinum salts and poly (ADP-ribose) polymerase (PARP) inhibitors. Early clinical experience with these agents has been promising, though response rates are variable and resistance through a variety of mechanisms can occur. Platforms to identify signatures of HR deficiency have gained increased attention and are being investigated as a tool for guiding treatment selection.

Summary

While a HR-deficient phenotype is increasingly recognized as being present in a significant portion of TNBCs, it is only recently that these advances are beginning to be translated into the clinical setting. Clinical studies are ongoing that will help to define the role of therapies targeting defective DNA repair pathways and biomarkers of HR deficiency in TNBC.

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  1. Department of Medicine, Division of Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, CC2241, Stanford, CA, 94305-5826, USA

    Alexey Aleshin & Melinda L. Telli

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  1. Alexey Aleshin
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Correspondence to Melinda L. Telli.

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Alexey Aleshin has no conflict of interest to declare.

Melinda L. Telli has served as an advisor for AstraZeneca, Tesaro, Vertex, Medivation, PharmaMar; has served as board member for Myraid Genetics; and reports her institution clinical research funding from Sanofi Aventis.

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Aleshin, A., Telli, M.L. Exploiting Homologous Recombination Deficiency in TNBC. Curr Breast Cancer Rep 9, 52–59 (2017). https://doi.org/10.1007/s12609-017-0236-9

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