ESR1 and breast cancer: In addition to the PI3K and MAPK pathways, MED1, which is an estrogen receptor binding protein, co-amplified with HER2, plays an important role as a critical mediator of HER2-driven breast tumorigenesis; this protein is a key crosstalk point for the HER2 and ER pathways in mediating the anti-estrogen resistance of HER2+/ER+ human breast cancer cells [378].