Antiestrogenic and antitumor effects of droloxifene in experimental breast carcinoma.

The pharmacological effects of droloxifene [E)-a [p-[2-(dimethylamino)ethoxy]phenyl]-a'-ethyl-3-stilbenol, FK435), a new antiestrogen drug, were studied and compared with those of tamoxifen in animals and in vitro cultured cells. Droloxifene showed about 20-fold and 3-fold higher affinity to estrogen receptors (ER) in the rat uterus and human ER positive MCF-7 breast carcinoma cells, respectively, than tamoxifen, and was more active in decreasing uterine weight of mature rats and 17 beta-estradiol-treated immature rats. Tamoxifen increased uterus growth in immature rats, but droloxifene did not, suggesting that droloxifene has no estrogenic effects. Both drugs inhibited the growth of in vitro cultured MCF-7 cells, with droloxifene being the more active agent, but this effect of both drugs was countered by 17 beta-estradiol. Neither drug, however, had effects on the in vitro growth of human ER negative MDA-MB-231 breast carcinoma cells. In vivo, both drugs inhibited the growth of MCF-7 carcinoma implanted subcutaneously in BALB/c nu/nu mice, but not the growth of human ER negative MX-1 breast carcinoma. The results suggest that droloxifene has antitumor effects on human ER positive breast cancers, and would be useful for the treatment of estrogen-dependent breast cancers.