Nature Communications (Aug 2023)

Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer

  • Lei-Jie Dai,
  • Ding Ma,
  • Yu-Zheng Xu,
  • Ming Li,
  • Yu-Wei Li,
  • Yi Xiao,
  • Xi Jin,
  • Song-Yang Wu,
  • Ya-Xin Zhao,
  • Han Wang,
  • Wen-Tao Yang,
  • Yi-Zhou Jiang,
  • Zhi-Ming Shao

DOI
https://doi.org/10.1038/s41467-023-40715-x
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 13

Abstract

Read online

Abstract The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibody‒drug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low breast cancer (433 female and one male) and integrated genomic, transcriptomic, proteomic, and metabolomic profiling data. In this cohort, HER2-low tumors are more distinguished from HER2-0 tumors in the hormone receptor–negative subgroup. Within HER2-low tumors, significant interpatient heterogeneity also exists in the hormone receptor–negative subgroup: basal-like tumors resemble HER2-0 disease, and non-basal-like HER2-low tumors mimic HER2-positive disease. These non-basal-like HER2-low tumors are enriched in the HER2-enriched subtype and the luminal androgen receptor subtype and feature PIK3CA mutation, FGFR4/PTK6/ERBB4 overexpression and lipid metabolism activation. Among hormone receptor–positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype.