ESR1 and breast fibrocystic disease: Although estrogen is thought to be involved in breast tumorigenesis in epidemiologic studies (Dall and Britt, 2017, Kelsey et al., 1993) and a combination of radiation and E2 treatment transformed normal mammary cells in vitro (Calaf and Hei, 2000), there is no experimental evidence showing that estrogen receptor α (ERα)-mediated estrogen signaling induces mammary dysplasia from normal mammary epithelial cells in vivo.