| HRA004845
(Controlled Access)
|
Hormone receptor positive HER2 negative (HR+/HER2-) is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. An accurate molecular classification is urgently required for precision treatment. Herein, we established the largest multi-omics cohort of Asian HR+/HER2- breast cancer to date. We introduced four novel molecular subtypes by integrating somatic copy number aberrations, somatic mutations, transcriptome, proteomics, metabolomics, and single-cell RNA sequencing of 583 HR+/HER2- breast cancers, namely canonical luminal, immunogenic, proliferative, and receptor tyrosine kinase (RTK)-driven subtypes. Each molecular subtype showed distinct biology, informed therapeutic strategies, and was validated in The Cancer Genome Atlas cohort. The RTK-driven subtype was featured by the activation of the RTK pathways and associated with endocrine therapy resistance. |
