Our current perspective for determining which patients may respond to anti-estrogen therapy is evolving, and is bolstered by findings that show that GPER associates with cancer progression variables (48, 52, 53), activates cellular receptors that facilitate cancer cell survival (54), promotes the survival of patient-derived breast cancer stem cells (59), and acts in the tumor microenvironment to drive cancer metastasis (62). This evidence concerns the gene GPER1 and breast cancer.