Trioxifene (LY133314) is a selective estrogen receptor modulator (SERM) with competitive binding activity against estradiol for estrogen receptor alpha (ERalpha) and antagonistic activity against ERalpha-mediated gene expression. Trioxifene has demonstrated activity in dimethyl-benzanthracene-induced mammary carcinoma in rats and human breast cancer patients. Trioxifene mesylate, an antiestrogen with a high FR affinity, was developed with the hope of improving the response rate of ER-positive patients, especially those with a borderline concentration of ER in their tumors. When used in vitro and in vivo, trioxifene has been shown to bind to the estradiol receptors with a binding affinity exceeding that of estradiol by a factor 1.7, whereas tamoxifen has a relative affinity of only 0.18 compared with trioxifene.