Results of association studies with E2 and BPA (~200 nM) indicate synergistic rather than additive activating effects on ERα, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), GPER, and phosphatase and tensin homolog (PTEN); and antagonizing effects on protein kinase B (Akt1) in breast cancer MCF-7 cells. This evidence concerns the gene PIK3CA and breast cancer.