ESR1 and breast cancer: As a result, tamoxifen is clinically used in ERα-positive breast cancers as an antagonist of estrogen signaling in mammary epithelial cells, yet it provides secondary ERα-agonist effects in bone, preventing osteoporosis (Rachner et al., 2018), and in endometrium, leading to an increased risk of endometrial cancer (Braun, Overbeek-Wager, and Grumbo 2016).