ESR1 and cancer: As it concerns breast malignancy, the role exerted by GPER should be carefully considered owing to its ability to bind not only estrogens but also ER antagonists such as 4-hydroxytamoxifen (OHT) and ICI 182,780, which elicit stimulatory effects particularly in ER-negative cancer cells (Filardo et al., 2000; Lappano et al., 2014; Pandey et al., 2009; Revankar et al., 2005).