ObjectiveTo investigate the causal relationship between 731 kinds of immune cells and positive-human epidermal growth factor receptor (HER+), negative-human epidermal growth factor receptor (HER–), negative-human epidermal growth factor receptor 2 (HER2–) breast cancer. MethodsGenome-wide association data for immune cells and breast cancer were used, and using inverse variance weighting as the primary analytical method, and Cochran’s Q test, Mendelian randomization (MR)-Egger regression, and leave-one-out were used to verify the reliability of the resulting data. ResultsFor HER+ breast cancer, CD3 on CD39+CD4+T cell [IVW: OR=0.940, 95%CI (0.913, 0.968), P<0.01], ratio of CD4–CD8–T cell [IVW: OR=0.906, 95%CI (0.857, 0.958), P<0.01], and CD3 on secreting CD4 regulatory T cell [IVW: OR=0.948, 95%CI (0.918, 0.979), P=0.01] were protective factors. For HER– breast cancer, no immune cell phenotype was found to be correlated with it. For HER2– breast cancer, CD3 on CD39+CD4+ T cell [IVW: OR=0.951, 95%CI (0.930, 0.973), P<0.01], CD3 on secreting CD4 regulatory T cell [IVW: OR=0.949, 95% CI (0.925, 0.974), P<0.01] were protective factors. ConclusionThere is a causal association between certain immune cell phenotypes and breast cancer, which may be a predictive marker for early diagnosis of breast cancer and development of new immunotherapies.