Two main classes of endocrine therapy exist: aromatase inhibitors, (AIs) such as letrozole, anastrozole (non-steroidal AI), and exemestane (steroidal AI), and antiestrogens: ER modulators (SERMs), their function is to block the activation of ERα in BC, as exemplified by tamoxifen (TAM, Nolvadex, Astra Zeneca, Cambridge, UK) [216], chlorinated derivative toremifene [217,218], and raloxifene [219]; and the selective ER downregulators (SERDs), which bind to ERα and leads to a reduced ERα level and activity due to its decay; for example, fulvestrant [220]. The gene discussed is ESR1; the disease is breast cancer.