Reversal of the antitumor effects of tamoxifen by progesterone in the 7,12-dimethylbenzanthracene-induced rat mammary carcinoma model.

Coadministration of progesterone (4 mg/day) opposed the antitumor activity of tamoxifen (100 micrograms/day) in rats bearing 7,12-dimethylbenzanthracene-induced tumors and also partially prevented the inhibition by tamoxifen (50 micrograms/day started 30 days after 7,12-dimethylbenzanthracene administration) of tumor occurrence even after tamoxifen therapy had been established for 1 or 2 mo. Although prolonged progesterone treatment raised progesterone levels, serum total estrogen levels were not raised above control. The reversal by progesterone of the inhibition of tumor occurrence produced by tamoxifen was blocked by the antiprogestin RU 486. These results demonstrate that progesterone can reverse the tumoristatic action of tamoxifen in the 7,12-dimethylbenzanthracene-induced tumor model and that this may be via a progesterone receptor-mediated mechanism.