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Toremifene given in different sizes of silastic capsules was used to treat MCF-7 tumors in athymic mice. Toremifene inhibited the estradiol-stimulated growth of MCF-7 tumors in athymic mice. Average serum concentrations of toremifene obtained using a sustained-release preparation of the drug (in 0.5-, 1.0-, and 2.0-cm silastic capsules) increased gradually in a capsule-size-dependent fashion. Much higher levels of toremifene or N-demethyl-toremifene were detected in tumors (target tissues of estrogen) as compared with muscles (non-target tissues of estrogen). The concentration of toremifene in serum (i.e., 10-30 ng ml-1) was sufficient to inhibit the estrogen-stimulated growth of MCF-7 tumors at physiological (i.e., 200-400 pg ml-1) serum estradiol concentrations in premenopausal women. No significant difference in estrogen receptor (ER) levels was found between the estradiol-alone group and the toremifene-treated groups. However, the ER levels in the toremifene-alone group and the no-treatment group (no toremifene or estradiol) tended to increase as compared with the estradiol-alone group. Toremifene blocked the estradiol-induced increase in progesterone receptor levels in a dose-dependent fashion. Insulin-like growth factor-1 (IGF-1) levels in the MCF-7 tumors significantly decreased in the toremifene-alone group as compared with the estradiol-alone group. These results show the antiestrogenic action of toremifene on hormone-dependent MCF-7 tumors in athymic mice. [ABSTRACT FROM AUTHOR]