ESR1 and cancer: The initial studies, which elucidated some of the biological actions exerted by GPER in breast cancer cells, like the activation of rapid intracellular signaling induced by E2 and the ER antagonists tamoxifen and ICI 182, 780 (13, 14, 20), paved the way for a wide number of studies aimed to characterize the molecular mechanisms involved in GPER-mediated biological responses like cancer cell growth, migration, and invasion.