B-Cell–Mediated Immunity Predicts Survival of Patients With Estrogen Receptor–Positive Breast Cancer

PURPOSE The estrogen receptor–positive (ER+) breast cancer (BC), which constitutes the majority of BC cases, exhibits highly heterogeneous clinical behavior. To aid precision treatments, we aimed to find molecular subtypes of ER+ BC representing the tumor microenvironment and prognosis. METHODS We analyzed RNA-seq data of 113 patients with BC and classified them according to the PAM50 intrinsic subtypes using gene expression profiles. Among them, we further focused on 44 patients with luminal-type (ER+) BC for subclassification. The Cancer Genome Atlas (TCGA) data of patients with BC were used as a validation data set to verify the new classification. We estimated the immune cell composition using CIBERSORT and further analyzed its association with clinical or molecular parameters. RESULTS Principal component analysis clearly divided the patients into two subgroups separately from the luminal A and B classification. The top differentially expressed genes between the subgroups were distinctly characterized by immunoglobulin and B-cell–related genes. We could also cluster a separate cohort of patients with luminal-type BC from TCGA into two subgroups on the basis of the expression of a B-cell–specific gene set, and patients who were predicted to have high B-cell immune activity had better prognoses than other patients. CONCLUSION Our transcriptomic approach emphasize a molecular phenotype of B-cell immunity in ER+ BC that may help to predict disease prognosis. Although further researches are required, B-cell immunity for patients with ER+ BC may be helpful for identifying patients who are good responders to chemotherapy or immunotherapy.