There is data to suggest that the aromatase inhibitor letrozole may have an indirect antitumor mechanism of action through reducing regulatory T lymphocytes (Tregs) in breast tumors [57] and that cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have multiple immunological effects in estrogen receptor (ER) + breast cancer [58]. This evidence concerns the gene ESR1 and breast cancer.