BACKGROUND: Globally, breast cancer is among the most frequent cancers, and tumor progression is greatly impacted by the immune system. Studies have revealed a correlation between the phenotypes of immune cells and the incidence of breast cancer
nevertheless, the causal relationship has yet to be fully elucidated. Hence, we sought to ascertain the causal relationship between immune cell subtypes and breast cancer through the implementation of Mendelian randomization (MR). METHODS: MR analysis utilized freely available genetic data to explore the causation link between 731 immune cell phenotypes and the susceptibility to breast cancer, distinguishing between estrogen receptor-positive (ER+) and negative (ER-) subtypes. ER+ patients are sensitive to endocrine drugs, and one more way to treat with endocrine drugs than ER- patients. Inverse variance weighting (IVW), MR-Egger regression, and weighted median methods were employed to evaluate MR. The IVW analysis was used as the primary research methodology. RESULTS: Among 731 immune phenotypes, we found that breast cancer was causally related to eight immune phenotypes, six of which were protective against breast cancer, while two were risk factors. After grouping breast cancers based on the ER expression, ER+ breast cancer patients were significantly causally related to seven immune phenotypes, among which three were protective against ER+ breast cancers, and four were risk factors. Furthermore, ER-breast cancer patients were significantly causally related to 10 immune phenotypes, with four being protective against ER-breast cancers and six being risk factors. CONCLUSIONS: This MR Study proved that there is a certain genetic relationship between immune cell phenotype and breast cancer, and the related genes may have certain significance for the treatment and drug development of breast cancer.