Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer
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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40715-x |
| _version_ | 1797558408465874944 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Lei-Jie Dai |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:30:05Z |
| format | Article |
| id | doaj.art-d72be25aa7d044a0b0ff35656eb21e54 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:30:05Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d72be25aa7d044a0b0ff35656eb21e542023-11-20T10:03:54ZengNature PortfolioNature Communications2041-17232023-08-0114111310.1038/s41467-023-40715-xMolecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancerLei-Jie Dai0Ding Ma1Yu-Zheng Xu2Ming Li3Yu-Wei Li4Yi Xiao5Xi Jin6Song-Yang Wu7Ya-Xin Zhao8Han Wang9Wen-Tao Yang10Yi-Zhou Jiang11Zhi-Ming Shao12Department of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Pathology, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterDepartment of Breast Surgery, Fudan University Shanghai Cancer CenterAbstract 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.https://doi.org/10.1038/s41467-023-40715-x |
| spellingShingle | 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 Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer Nature Communications |
| title | Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer |
| title_full | Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer |
| title_fullStr | Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer |
| title_full_unstemmed | Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer |
| title_short | Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer |
| title_sort | molecular features and clinical implications of the heterogeneity in chinese patients with her2 low breast cancer |
| url | https://doi.org/10.1038/s41467-023-40715-x |
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