ESR1 and breast carcinoma: Activation of GPER leads to the activation of downstream pathways that, depending on the cell type, are associated with both proliferation24, 25 and apoptosis.26 A very interesting study has highlighted the opposite effects played by GPER activation on cell proliferation of ER-negative and ER-positive breast cancer cells.27 Specifically, when ERs are expressed, the activation of GPER leads to inhibition of cell proliferation.