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. 2023 Oct;55(10):1696-1708.
doi: 10.1038/s41588-023-01507-7. Epub 2023 Sep 28.

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

Xi Jin #  1 , Yi-Fan Zhou #  1 , Ding Ma #  1 , Shen Zhao #  1 , Cai-Jin Lin #  1 , Yi Xiao  1 , Tong Fu  1 , Cheng-Lin Liu  1 , Yi-Yu Chen  1 , Wen-Xuan Xiao  1 , Ya-Qing Liu  2 , Qing-Wang Chen  2 , Ying Yu  2 , Le-Ming Shi  2   3 , Jin-Xiu Shi  4 , Wei Huang  4 , John F R Robertson  5 , Yi-Zhou Jiang #  6 , Zhi-Ming Shao  7
Affiliations

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

Xi Jin et al. Nat Genet. 2023 Oct.

Abstract

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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