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Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer

Author

Listed:
  • Paolo Tarantino

    (Medical Oncology, Dana-Farber Cancer Institute
    Dana-Farber Brigham Cancer Center
    Harvard Medical School
    University of Milano)

  • Hersh Gupta

    (Medical Oncology, Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Melissa E. Hughes

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Janet Files

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Sarah Strauss

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Gregory Kirkner

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Anne-Marie Feeney

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Yvonne Li

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Ana C. Garrido-Castro

    (Medical Oncology, Dana-Farber Cancer Institute
    Dana-Farber Brigham Cancer Center
    Harvard Medical School)

  • Romualdo Barroso-Sousa

    (Dasa Institute for Education and Research (IEPD)
    Dasa Oncology/Hospital Brasilia)

  • Brittany L. Bychkovsky

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

  • Simona DiLascio

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Lynette Sholl

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Laura MacConaill

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Neal Lindeman

    (Medical Oncology, Dana-Farber Cancer Institute
    Weill Cornell Medicine)

  • Bruce E. Johnson

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Matthew Meyerson

    (Medical Oncology, Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Rinath Jeselsohn

    (Medical Oncology, Dana-Farber Cancer Institute
    Dana-Farber Brigham Cancer Center
    Harvard Medical School)

  • Xintao Qiu

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Rong Li

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Henry Long

    (Medical Oncology, Dana-Farber Cancer Institute)

  • Eric P. Winer

    (Smilow Cancer Hospital)

  • Deborah Dillon

    (Harvard Medical School
    Brigham and Women’s Hospital)

  • Giuseppe Curigliano

    (European Institute of Oncology IRCCS)

  • Andrew D. Cherniack

    (Medical Oncology, Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Sara M. Tolaney

    (Medical Oncology, Dana-Farber Cancer Institute
    Dana-Farber Brigham Cancer Center
    Harvard Medical School)

  • Nancy U. Lin

    (Medical Oncology, Dana-Farber Cancer Institute
    Dana-Farber Brigham Cancer Center
    Harvard Medical School)

Abstract

The molecular underpinnings of HER2-low and HER2-0 (IHC 0) breast tumors remain poorly defined. Using genomic findings from 1039 patients with HER2-negative metastatic breast cancer undergoing next-generation sequencing from 7/2013-12/2020, we compare results between HER2-low (n = 487, 47%) and HER2-0 tumors (n = 552, 53%). A significantly higher number of ERBB2 alleles (median copy count: 2.05) are observed among HER2-low tumors compared to HER2-0 (median copy count: 1.79; P = 2.36e-6), with HER2-0 tumors harboring a higher rate of ERBB2 hemideletions (31.1% vs. 14.5%). No other genomic alteration reaches significance after accounting for multiple hypothesis testing, and no significant differences in tumor mutational burden are observed between HER2-low and HER2-0 tumors (median: 7.26 mutations/megabase vs. 7.60 mutations/megabase, p = 0.24). Here, we show that the genomic landscape of HER2-low and HER2-0 tumors does not differ significantly, apart from a higher ERBB2 copy count among HER2-low tumors, and a higher rate of ERBB2 hemideletions in HER2-0 tumors.

Suggested Citation

  • Paolo Tarantino & Hersh Gupta & Melissa E. Hughes & Janet Files & Sarah Strauss & Gregory Kirkner & Anne-Marie Feeney & Yvonne Li & Ana C. Garrido-Castro & Romualdo Barroso-Sousa & Brittany L. Bychkov, 2023. "Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43324-w
    DOI: 10.1038/s41467-023-43324-w
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    References listed on IDEAS

    as
    1. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
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