Effective sequential administration of tamoxifen and medroxyprogesterone acetate for 7,12-dimethylbenz[a-anthracene-induced rat mammary tumors in relation to hormone receptors.

Abstract

The effects of two hormonal agents with different mechanisms of action, medroxyprogesterone acetate (MPA) and tamoxifen (TAM), on the tumor growth and hormone receptor status were evaluated in rat mammary tumors induced by 7,12-dimethylbenz[alpha]anthracene (DMBA). All estrogen receptor-positive (ER(+)) tumors became ER-negative (ER(-)), and 3 out of 4 progesterone receptor-negative (PgR(-)) and ER(+) tumors became PgR-positive (PgR(+)) after daily, oral administration of TAM for 2 weeks. In contrast, ER and PgR remained unchanged after daily administration of MPA for 2 to 4 weeks. All the ER(+) and PgR(-) tumors were transformed into PgR(+) after daily treatment with MPA for 2 weeks and then with TAM for another 2 weeks, but tumor regression was modest and none disappeared completely. In contrast, complete remission was achieved in all ER(+) tumors in the group treated with TAM for 2 weeks and then with MPA for another 2 weeks. The results suggest that the antitumor activity of the latter treatment regimen was significantly higher than that of the former. The possible mechanisms of antitumor activity of two hormonal agents are discussed.