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Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

Author

Listed:
  • Tanya E. Keenan

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Jennifer L. Guerriero

    (Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • Romualdo Barroso-Sousa

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center
    Hospital Sírio-Libanês)

  • Tianyu Li

    (Dana-Farber Cancer Institute, Boston)

  • Tess O’Meara

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Anita Giobbie-Hurder

    (Dana-Farber Cancer Institute, Boston)

  • Nabihah Tayob

    (Dana-Farber Cancer Institute, Boston)

  • Jiani Hu

    (Dana-Farber Cancer Institute, Boston)

  • Mariano Severgnini

    (Dana-Farber Cancer Institute)

  • Judith Agudo

    (Dana-Farber Cancer Institute)

  • Ines Vaz-Luis

    (Institut Gustave Roussy)

  • Leilani Anderson

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Victoria Attaya

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Jihye Park

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Jake Conway

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Meng Xiao He

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard
    Harvard Graduate Program in Biophysics)

  • Brendan Reardon

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Erin Shannon

    (Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Gerburg Wulf

    (Beth Israel Deaconess Medical Center)

  • Laura M. Spring

    (Massachusetts General Hospital)

  • Rinath Jeselsohn

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Ian Krop

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Nancy U. Lin

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Ann Partridge

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Eric P. Winer

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

  • Elizabeth A. Mittendorf

    (Dana-Farber/Brigham and Women’s Cancer Center
    Dana-Farber Cancer Institute
    Brigham and Women’s Hospital
    Harvard Medical School)

  • David Liu

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Eliezer M. Van Allen

    (Dana-Farber Cancer Institute
    Broad Institute of Massachusetts Institute of Technology and Harvard)

  • Sara M. Tolaney

    (Dana-Farber Cancer Institute
    Dana-Farber/Brigham and Women’s Cancer Center)

Abstract

Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59–1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.

Suggested Citation

  • Tanya E. Keenan & Jennifer L. Guerriero & Romualdo Barroso-Sousa & Tianyu Li & Tess O’Meara & Anita Giobbie-Hurder & Nabihah Tayob & Jiani Hu & Mariano Severgnini & Judith Agudo & Ines Vaz-Luis & Leil, 2021. "Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25769-z
    DOI: 10.1038/s41467-021-25769-z
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