Thus, the ERα:ERβ ratio was not greatly affected by E2, however, fulvestrant and 4-OHT greatly reduced the ERα:ERβ ratio confirming their beneficial effects in ER+ BC (Leclercq et al., 2006; Sotoca Covaleda et al., 2008; Pons et al., 2014; Acconcia et al., 2017). This evidence concerns the gene ESR2 and breast cancer.