Interestingly, tamoxifen (TAM), a selective ER modulator (SERM) targeting ERα, and its metabolite 4-hydroxytamoxifen have been recognized as agonists of GPER (Prossnitz & Barton 2011, Vivacqua et al. 2012), indicating a potential role of GPER in breast cancer TAM resistance. This evidence concerns the gene ESR1 and breast carcinoma.