EFFECT OF CONJOINT ADMINISTRATION OF TAMOXIFEN AND HIGH-DOSE RADIATION ON THE DEVELOPMENT OF MAMMARY-CARCINOMA

Purpose: Tamoxifen is currently advocated for post-menopausal breast c ancer patients receiving definitive irradiation after limited surgery. The purpose of this study was to assess in an experimental model for breast cancer whether the efficacy of irradiation is altered by conjoi nt administration of tamoxifen. To this end, rats with small tumors in duced by 1-methyl-1-nitrosourea (MNU) were treated with tamoxifen, rad iation, or a combination of the two modalities. Methods and Materials: Female Sprague Dawley rats were injected i.p. with 50 mg MNU/kg body weight at 50 days of age. At 64 days post carcinogen, the majority of the rats had at least one palpable mammary tumor. At that time radiati on with or without tamoxifen treatment was initiated and given 5 days per week for 5 weeks. Radiation dose was 4500 cGy delivered as 25, 180 cGy fractions. Tamoxifen, 500 mg/kg body weight, was administered sub cutaneously each day during the irradiation interval. The study was te rminated 28 weeks after carcinogen treatment. Results: High dose radia tion alone induced a reduction in the size of existing tumors, but res ulted in a significant increase in the number of tumors that were dete cted. Treatment with tamoxifen alone also caused a reduction in tumor volume, but had no effect on final incidence or number of mammary tumo rs. Combined modality treatment resulted in a significant reduction in the volume of existing tumors and suppressed the enhanced occurrence of additional tumors observed when only radiation alone was administer ed. Conclusion: The findings of this study indicate that in the contex t of fractionated, high dose radiation treatment of established mammar y cancers, tamoxifen may reduce the likelihood of subsequent tumor dev elopment and by so doing prove a helpful simultaneous conjoint adjuvan t treatment to post-operative irradiation.