The Effect of Ovariectomy, Tamoxifen and the Combination Adriamycin and 5-FU on 7,12-Dimethylbenz(a)anthracene Induced Mammary Cancer of the Rat

Abstract

This study was carried out in order to compare the therapeutic effect of ovariectomy, of the antiestrogen tamoxifen and of the combination adriamycin and 5-fluorouracil (5-FU) in 7,12-dimethylbenz (a) anthracene (DMBA) induced premenopausal mammary cancer. 74 rats were randomized to receive (A) ovariectomy, (B) tamoxifen 14 mg/m², day 1–21, per os, (C) Tamoxifen 2,1 mg/m2, day 1–21, per os, (D) combination chemotherapy of adriamycin and 5-FU and (E) no therapy. 72 rats were evaluable. Ovariectomy was the most effective treatment resulting in five (36 %) complete and seven (50 %) partial remissions out of 14. Tamoxifen (B) yielded one (7 %) partial remission and seven (47 %) no changes out of 13 treated rats. Median tumor size was 0.5 g after ovariectomy and 3.9 g after tamoxifen (B) respectively. The level of significance was p < 0.001 for remmission rate and p < 0.001 for tumor size in favor of ovariectomy. Regimen (C) of tamoxifen showed marginal activity. Only minimal toxic effects could be observed after treatment with tamoxifen. The combination of adriamycin and 5-FU was somewhat more effective than tamoxifen but significantly (p < 0.05) less active than ovariectomy. The results obtained in this experimental model for mammary cancer suggest that tamoxifen cannot replace ovariectomy as the first endocrine therapy in the treatment of advanced mammary cancer in premenopausal women.