Molecular classification of hormone receptor-positive HER2-negative breast cancer

被引:0
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作者
Xi Jin
Yi-Fan Zhou
Ding Ma
Shen Zhao
Cai-Jin Lin
Yi Xiao
Tong Fu
Cheng-Lin Liu
Yi-Yu Chen
Wen-Xuan Xiao
Ya-Qing Liu
Qing-Wang Chen
Ying Yu
Le-Ming Shi
Jin-Xiu Shi
Wei Huang
John F. R. Robertson
Yi-Zhou Jiang
Zhi-Ming Shao
机构
[1] Fudan University Shanghai Cancer Center,Key Laboratory of Breast Cancer, Department of Breast Surgery
[2] Fudan University,State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute and Shanghai Cancer Center
[3] International Human Phenome Institutes (Shanghai),Shanghai
[4] Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT),MOST Key Laboratory of Health and Disease Genomics
[5] University of Nottingham,undefined
[6] Royal Derby Hospital,undefined
来源
Nature Genetics | 2023年 / 55卷
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摘要
Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR+/HER2− breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR+/HER2− breast cancer.
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页码:1696 / 1708
页数:12
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