E2 can suppress ECM production in breast cancer cells through GPR30-mediated inhibition of MAPK and Smad signaling,37 in diabetic nephropathy models by modulating TGF-β downstream signaling and suppressing type I and IV collagen accumulation,38 and in dermal fibroblasts by inhibiting TGF-β-dependent activation and collagen production through decreased Smad2/3 phosphorylation.14 This evidence concerns the gene SMAD2 and breast cancer.