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Emerging therapeutic modalities of PARP inhibitors in breast cancer

  • Author Footnotes
    1 Xin Wang, Yaqin Shi contributed equally to this manuscript.
    Xin Wang
    Footnotes
    1 Xin Wang, Yaqin Shi contributed equally to this manuscript.
    Affiliations
    Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
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  • Author Footnotes
    1 Xin Wang, Yaqin Shi contributed equally to this manuscript.
    Yaqin Shi
    Footnotes
    1 Xin Wang, Yaqin Shi contributed equally to this manuscript.
    Affiliations
    Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
    Search for articles by this author
  • Doudou Huang
    Affiliations
    Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China
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  • Xiaoxiang Guan
    Correspondence
    Corresponding author at: Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing 210002, China.
    Affiliations
    Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

    Department of Medical Oncology, Jinling Clinical College, Nanjing Medical University, Nanjing 210002, China
    Search for articles by this author
  • Author Footnotes
    1 Xin Wang, Yaqin Shi contributed equally to this manuscript.

      Highlights

      • Platinum-PARPi combination use is promising in metastatic BRCA mutated breast cancer or TNBC.
      • Such combination use was demonstrated with no superiority in neoadjuvant setting of TNBC.
      • We provided promising prospects of PARPi as maintenance therapy in breast cancer.

      Abstract

      Inhibition of Poly (ADP-ribose) polymerase (PARP) has shown marked benefit for breast cancer with homologous recombination deficiency, whether driven by defects in BRCA1, BRCA2, or other pathway components. Since the initial approval of olaparib, a mostly investigated PARP inhibitor (PARPi), the clinical development of PARPi in breast cancer treatment has been a major emphasis. Researches in investigating platinum-PARPi combination use compared with platinum monotherapy demonstrated promising benefit in metastatic BRCA mutated breast cancer or TNBC, while no such superiority was observed in the neoadjuvant setting of TNBC. Moreover, the utility of PARP inhibition in BRCA1/2 mutated breast cancer with different platinum-free interval was investigated. There was a clear association between clinical benefit with PARPi and platinum sensitivity, whereas partial efficacy of PARPi still occurs in platinum-resistant patients. In addition, proof-of-principle studies of immunotherapy combined with PARPi in breast cancer have obtained promising results, indicating the potential benefit of the combination therapy in patients with breast cancer. These efforts, contributing to maximize the utility of PARPi, may drive a new era of this agent after its first routine use. In this review, we summarized the utility of combining platinum-PARPi in BRCA mutated breast cancer or TNBC compared with platinum monotherapy and provided promising prospects of PARPi as maintenance therapy in breast cancer, as well as providing a strong rationale for testing immunotherapy combined with PARPi in breast cancer to expand the clinical utility of PARPi.

      Keywords

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