Comprehensive genomic characterization of HER2-low and HER2-0 breast cancer
Paolo Tarantino, Hersh Gupta, Melissa E. Hughes, Janet Files, Sarah Strauss, Gregory J. Kirkner, Anne-Marie Feeney, Yvonne Li, Ana C. Garrido-Castro, Romualdo Barroso‐Sousa, Brittany Bychkovsky, Simona Di Lascio, Lynette M. Sholl, Laura E. MacConaill, Neal Lindeman, Bruce E. Johnson, Matthew Meyerson, Rinath Jeselsohn, Xintao Qiu, Rong Li, Henry W. Long, Eric P. Winer, Deborah Dillon, Giuseppe Curigliano, Andrew D. Cherniack, Sara M. Tolaney, Nancy U. Lin
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.