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

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Listed:
  • Lei-Jie Dai

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Ding Ma

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Yu-Zheng Xu

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Ming Li

    (Fudan University Shanghai Cancer Center)

  • Yu-Wei Li

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Yi Xiao

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Xi Jin

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Song-Yang Wu

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Ya-Xin Zhao

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Han Wang

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Wen-Tao Yang

    (Fudan University Shanghai Cancer Center)

  • Yi-Zhou Jiang

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

  • Zhi-Ming Shao

    (Fudan University Shanghai Cancer Center
    Fudan University Shanghai Cancer Center
    Shanghai Medical College, Fudan University)

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.

Suggested Citation

  • 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, 2023. "Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40715-x
    DOI: 10.1038/s41467-023-40715-x
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    1. Christina Curtis & Sohrab P. Shah & Suet-Feung Chin & Gulisa Turashvili & Oscar M. Rueda & Mark J. Dunning & Doug Speed & Andy G. Lynch & Shamith Samarajiwa & Yinyin Yuan & Stefan Gräf & Gavin Ha & Gh, 2012. "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups," Nature, Nature, vol. 486(7403), pages 346-352, June.
    2. Chisato M. Yamazaki & Aiko Yamaguchi & Yasuaki Anami & Wei Xiong & Yoshihiro Otani & Jangsoon Lee & Naoto T. Ueno & Ningyan Zhang & Zhiqiang An & Kyoji Tsuchikama, 2021. "Antibody-drug conjugates with dual payloads for combating breast tumor heterogeneity and drug resistance," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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