Based on the molecular expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), breast cancer can be separated into four major subgroups: (1) luminal A that is positive for ERα and PR and without HER2 amplification; (2) luminal B that is positive for both ERα, PR, and amplified HER2; (3) HER2-amplified cancer that is negative for ERα; and (4) basal-like cancer in which the majority of the cases, approximately 75–80%, are triple-negative for ERα, PR and HER2 and referred to as triple-negative breast cancer (TNBC). This evidence concerns the gene ESR1 and cancer.