E4 was also shown to trigger rapid non-genomic effects regardless of ERα, like the activation of the MAPK ERK1/2 and PI3K/AKT pathways in breast cancer cells [25] as well as the GPER-mediated phosphorylation of the focal adhesion kinase (FAK) in endothelial cells [25, 29]. Here, ESR1 is linked to breast cancer.