In addition to E2, TAM as well as its metabolite, 4-OH-TAM, have also high-affinity binding to GPER and can activate the receptor [104,105,106,107], thus inducing rapid cellular signaling, including ERK activation, PI3K activation, calcium mobilization and cAMP production in breast cancer cells [98,105] (Figure 5). This evidence concerns the gene GPER1 and breast carcinoma.