Experimental chemo- and chemoendocrine therapy of human breast carcinomas serially transplanted into nude mice

Four human breast carcinoma strains serially transplanted into nude mice were used for the experimental chemotherapy and combination chemoendocrine therapy. Whereas three of these strains (MCF-7, Br-10, TM-61) possessed cytosol estrogen receptor (ERc) and were dependent on estradiol for the tumor growth, the other strain (MX-1) without ERc was hormone independent. For the chemotherapy, mitomycin C (MMC), adriamycin (ADM), cyclophosphamide (CPM) and 5-fluorouracil (5-FU) were administered 3 times every 4 days. To know the stability of ERc after chemotherapy, binding sites of ERc were measured 4 days after MMC administration at doses of 1, 2 and 4.5 mg/kg. For the chemoendocrine therapy, 1 or 2 mg/kg of MMC was administered once followed by treatment by tamoxifen (TAM). The effect of treatment was evaluated by T/C ratio of the tumor weight. MMC showed the most excellent antitumor effect and CPM and ADM showed a moderate effect. As ERc was found to be stable by MMC treatment, TAM was used after MMC, and this combination of MMC and TAM revealed an additive effect against ERc positive strains and no combination effect was observed in MX-1 without ERc. The dose response curves of 4 strains to MMC alone against 4 strains were made and the effect of combination chemoendocrine therapy was converted to the effect of MMC alone, showing the dose of MMC could be significantly reduced. Binding sites of ERc which were measured 4 days after MMC administration (1, 2 and 4.5 mg/kg) was found to be stable, suggesting TAM treatment after MMC might be reasonable. From these results, chemoendocrine therapy of MMC followed by TAM was considered to be beneficial modality for clinical treatment of the cytotoxic agent and increasing the antitumor effect.