ESR1 and breast cancer: Although antagonistic actions of E4 have been reported in several tissues including the brain (Pluchino et al., 2014; Gérard et al., 2015a,b; Pluchino et al., 2015), whether these effects are mediated by transcriptional or membrane ERα signaling is not known, with the exception of the membrane-mediated action identified in endothelial and breast cancer cells (Abot et al., 2014; Giretti et al., 2014) and in the brain (de Bournonville et al., 2023).