ESR1 and breast cancer: While an association between a hormonal response and COX-2 expression and activity has been known for a few years (i.e. mammary glands of pregnant and E2 plus P4 treated rats, DMBA-induced rat mammary tumor growth, and in ER+ breast cancer cells) [58–60], the recent clinical data collectively suggest COX-2 may be an important driver of ER+ breast cancer progression.