ESR1 and breast carcinoma: The tamoxifen metabolite 4-hydroxytamoxifen (4-OHT) competes with estradiol (E2) at the ligand-binding site of ER, and 4-OHT-ER complexes that enter the nucleus bind to ERE regions and recruit corepressors, which leads to blocking a subset of E2-inducible genes and inhibits the growth of ER-containing breast cancer cells (Figure 3A).