In addition, the selective activation of GPER by its synthetic ligand G-1 mediates anti-angiogenic effects by repressing the HIF-1α/VEGF signaling in the triple negative MDA-MB-231 breast cancer cells [201], thus suggesting that the tumor promoting/tumor suppressive role of the HIF-1α/GPER signaling in breast cancer may at least in part depend on the ER and HER2 status. This evidence concerns the gene ERBB2 and breast cancer.