Of note, the mechanisms through which GPER might be involved in the aggressive malignant features were extended to the ability of estrogenic GPER signaling to induce the HIF1α-dependent expression of vascular endothelial growth factor (VEGF) toward breast tumor angiogenesis (De Francesco et al., 2013a,b, , 2014; Filice et al., 2009; Recchia et al., 2011). This evidence concerns the gene HIF1A and breast neoplasm.