Antitumor actions of toremifene in the 7,12-dimethylbenzanthracene (DMBA)-induced rat mammary tumor model.

Toremifene (200 and 800 micrograms/day) or tamoxifen (200 micrograms) were effective in preventing the development of 7,12-dimethylbenzanthracene-induced rat mammary tumors when given p.o. from day 28 after carcinogen administration. This antitumor action was completely reversed if the toremifene or tamoxifen treatment was stopped or partially reversed by coadministration of progesterone (4 mg/day). Large doses of toremifene (4000 and 8000 micrograms/day) for 10 days produced very high circulating levels of the parent compound (282 +/- 49 and 1002 +/- 224 ng/ml, respectively) and N-desmethyltoremifene (2631 +/- 449 and 6999 +/- 1308 ng/ml, respectively). However, even these very high levels did not reduce the number of animals ultimately developing tumors or the number of tumors each animal developed following cessation of toremifene administration. These findings indicate toremifene has a tumoristatic rather than tumoricidal action in this tumor model.