Antitumor effect of the antiestrogen, tamoxifen, ona pregnancy-dependent mouse mammary tumor (TPDMT-4).

TPDMT-4 mammary tumors, characterized by growth during pregnancy and regression after delivery, show continued growth in female DDD mice carrying pituitary isografts ectopically or a s.c. 17 beta-estradiol-plus-progesterone pellet. These experimental models were used to investigate the antitumor effect of the nonsteroidal antiestrogen tamoxifen. When tumors grew to significant sizes, tamoxifen was injected s.c. at a daily dose of 800, 400, 200, 100, 50, 5 or 1 micrograms three times weekly. In pituitary isograft-bearing mice the antitumor effect of tamoxifen at the three highest doses was comparable to that of ovariectomy: tumors regressed slowly during the first 2 weeks of treatment and subsequently more rapidly. Tamoxifen at 100 and 50 micrograms had no influence on tumor growth during the first 2 weeks and subsequently gave rise to rapid regression. The antiestrogen suppressed tumor growth throughout the treatment period at 10 micrograms, but it had no effect on growth at the two lowest doses. Tamoxifen caused atrophy of the ovaries and mammary glands in a dose-related manner, that of luteal components in the former being especially conspicuous at 200-micrograms doses and higher. In pellet-carrying mice, tamoxifen suppressed tumor growth completely at 800 micrograms but partially and insignificantly at 200 micrograms. Growth of PIMT-16 autonomous mammary tumors included for comparison was not affected either by tamoxifen at 800 micrograms daily or by ovariectomy. Tamoxifen is suggested to exert an antitumor effect on this particular hormone-dependent mammary tumor model through its direct action on tumor cells and its suppressive action on hormone production by the ovaries and pituitary gland.