ESR1 and breast cancer: As for estrogen receptor (ER), D. Feldman's group has shown that 1α,25(OH)2D3 exerts a multilevel protective effect against breast cancer that includes the inhibition of estrogen synthesis through the direct and indirect repression of aromatase (CYP19) and the downregulation of ER-α expression through two VDREs in its promoter region (Krishnan et al., 2010; Swami et al., 2013).