Precise subtyping reveals immune heterogeneity for hormone receptor-positive breast cancer.

A significant proportion of breast cancer cases are characterized by hormone receptor positivity (HR+). Clinically, the heterogeneity of HR+ breast cancer leads to different therapeutic effects on endocrine. Therefore, definition of subgroups in HR+ breast cancer is important for effective treatment. Here, we have developed a CMBR method utilizing computational functional networks based on DNA methylation to identify conserved subgroups in HR+ breast cancer. Calculated by CMBR, HR+ breast cancer was divided into five subgroups, of which HR+/negative epidermal growth factor receptor-2 (Her2-) was divided into two subgroups, and HR+/positive epidermal growth factor receptor-2 (Her2+) was divided into three subgroups. These subgroups had heterogeneity in the immune microenvironment, tumor infiltrating lymphocyte patterns, somatic mutation patterns and drug sensitivity. Specifically, CMBR identified two subgroups with the "Hot" tumor phenotype. In addition, these conserved subgroups were broadly validated on external validation datasets. CMBR identified the molecular signature of HR+ breast cancer subgroups, providing valuable insights into personalized treatment strategies and management options.