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

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. Bychkovsky, Simona DiLascio, Lynette Sholl, Laura MacConaill, Neal Lindeman, Bruce E. Johnson, Matthew Meyerson, Rinath Jeselsohn, Xintao Qiu, Rong Li, Henry Long, Eric P. Winer, Deborah Dillon, Giuseppe Curigliano, Andrew D. Cherniack, Sara M. Tolaney and Nancy U. Lin
Additional contact information
Paolo Tarantino: Medical Oncology, Dana-Farber Cancer Institute
Hersh Gupta: Medical Oncology, Dana-Farber Cancer Institute
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
Romualdo Barroso-Sousa: Dasa Institute for Education and Research (IEPD)
Brittany L. Bychkovsky: Dana-Farber Brigham Cancer Center
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
Bruce E. Johnson: Medical Oncology, Dana-Farber Cancer Institute
Matthew Meyerson: Medical Oncology, Dana-Farber Cancer Institute
Rinath Jeselsohn: Medical Oncology, Dana-Farber Cancer Institute
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
Giuseppe Curigliano: European Institute of Oncology IRCCS
Andrew D. Cherniack: Medical Oncology, Dana-Farber Cancer Institute
Sara M. Tolaney: Medical Oncology, Dana-Farber Cancer Institute
Nancy U. Lin: Medical Oncology, Dana-Farber Cancer Institute

Nature Communications, 2023, vol. 14, issue 1, 1-10

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43324-w

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