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

Nat Commun. 2023 Aug 22;14(1):5112. doi: 10.1038/s41467-023-40715-x.

Authors

Lei-Jie Dai^#^{1

2

3}, Ding Ma^#^{4

5

6}, Yu-Zheng Xu^#^{1

2

3}, Ming Li^#⁷, Yu-Wei Li^{1

2

3}, Yi Xiao^{1

2

3}, Xi Jin^{1

2

3}, Song-Yang Wu^{1

2

3}, Ya-Xin Zhao^{1

2

3}, Han Wang^{1

2

3}, Wen-Tao Yang⁸, Yi-Zhou Jiang^{9

10

11}, Zhi-Ming Shao^{12

13

14}

Affiliations

¹ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
² Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
³ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
⁴ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dma09@fudan.edu.cn.
⁵ Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dma09@fudan.edu.cn.
⁶ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. dma09@fudan.edu.cn.
⁷ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
⁸ Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. yangwt2000@163.com.
⁹ Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. yizhoujiang@fudan.edu.cn.
¹⁰ Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. yizhoujiang@fudan.edu.cn.
¹¹ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. yizhoujiang@fudan.edu.cn.
¹² Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. zhimingshao@fudan.edu.cn.
¹³ Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. zhimingshao@fudan.edu.cn.
¹⁴ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. zhimingshao@fudan.edu.cn.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
East Asian People
Female
Gene Expression Profiling
Humans
Male
Proteomics