GROWTH-INHIBITION OF DMBA-INDUCED RAT MAMMARY CARCINOMAS BY THE ANTIANDROGEN FLUTAMIDE

Antiandrogens have sporadically been reported to exert antitumor activ ities in both pre- and post-menepausal breast cancer. To explore the p ossibility of using the pure antiandrogen flutamide (FLU) in breast ca ncer therapy, rats bearing DMBA-induced mammary tumors were treated wi th FLU, dihydrotestosterone (DHT), or FLU plus DHT. FLU was administer ed orally, at doses comparable to those used in the treatment of prost ate cancer patients. FLU-treated animals had a significantly smaller a verage tumor area than controls from day 11 up to the end of the exper iment (day 20). A similar reduction of tumor growth was observed in ra ts given DHT and in those treated with DHT plus FLU. Plasma levels of LH, FSH, P, 17-OH P, E(2) and DHEA measured at the end of experiment d id not differ between treated animals and controls. Results demonstrat e that the antiandrogen FLU and the full androgen DHT exert similar in hibitory effects on the growth of dimethylbenz(a)anthracene (DMBA)-ind uced rat mammary tumors. Moreover, data show that plasma steroids leve ls are unaffected by FLU treatment. This finding rules out any antitum or effect dependent on the reduction of adrenal and gonadal steroidosy nthesis, and makes it appear more likely that androgen receptors are i nvolved in the antiproliferative effect of FLU.