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p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases

Author

Listed:
  • Jing Ni

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Sheheryar Kabraji

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Harvard Medical School)

  • Shaozhen Xie

    (Dana-Farber Cancer Institute
    Harvard Medical School)

  • Yanzhi Wang

    (Dana-Farber Cancer Institute)

  • Peichen Pan

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Zhejiang University)

  • Xiaofang He

    (Dana-Farber Cancer Institute
    the first affiliated hospital of Sun Yat-Sen University)

  • Zongming Liu

    (Dana-Farber Cancer Institute
    College of Biological and Agricultural Engineering, Jilin University
    Jilin Cancer Hospital)

  • Jose Palbo Leone

    (Dana-Farber Cancer Institute)

  • Henry W. Long

    (Dana-Farber Cancer Institute)

  • Myles A. Brown

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute)

  • Eric P. Winer

    (Dana-Farber Cancer Institute)

  • Deborah A. R. Dillon

    (Brigham and Women’s Hospital)

  • Nancy U. Lin

    (Dana-Farber Cancer Institute)

  • Jean J. Zhao

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Harvard Medical School)

Abstract

Approximately 50% of patients with metastatic HER2-positive (HER2+) breast cancer develop brain metastases (BCBMs). We report that the tumor suppressor p16INK4A is deficient in the majority of HER2+ BCBMs. p16INK4A-deficiency as measured by protein immunohistochemistry predicted response to combined tucatinib and abemaciclib in orthotopic patient-derived xenografts (PDXs) of HER2 + BCBMs. Our findings establish the rationale for a biomarker-driven clinical trial of combined CDK4/6- and HER2-targeted agents for patients with HER2 + BCBM.

Suggested Citation

  • Jing Ni & Sheheryar Kabraji & Shaozhen Xie & Yanzhi Wang & Peichen Pan & Xiaofang He & Zongming Liu & Jose Palbo Leone & Henry W. Long & Myles A. Brown & Eric P. Winer & Deborah A. R. Dillon & Nancy U, 2022. "p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29081-2
    DOI: 10.1038/s41467-022-29081-2
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