ESR1 and breast carcinoma: Importantly, breast cancer cell-based studies revealed that the Y537S and D538G mutations conferred hormone-independent activation of ERα and reduced the inhibitory potency and efficacy of clinically prescribed SERMs and SERDs (Toy et al., 2013; Merenbakh-Lamin et al., 2013; Robinson et al., 2013; Li et al., 2013; Jeselsohn et al., 2014; Carlson et al., 1997).