Nature Communications (Nov 2023)

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,
  • Nancy U. Lin

DOI
https://doi.org/10.1038/s41467-023-43324-w
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 10

Abstract

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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.