Long-term tamoxifen adjuvant therapy in node-positive breast cancer: a metabolic and pilot clinical study.

One hundred twenty-four disease-free postoperative women with ipsilateral-node-positive breast carcinoma were evaluated to assess the metabolic handling and clinical side effects of adjuvant tamoxifen for periods in excess of five years. The patients received postoperative combination chemotherapy for a median of 14 months. Thirty-eight patients received no tamoxifen. Tamoxifen 10 mgs bid was administered to 86 patients during the chemotherapy duration and has been continued in 43 of these patients for up to five years after termination of chemotherapy. Serum samples obtained in 7 patients at 3 to 4-month intervals during the first 5 years revealed that levels of tamoxifen, N-desmethyltamoxifen, and metabolite Y were generally constant throughout the period of drug administration. There was no difference in side effects observed after stopping chemotherapy between the group continuing tamoxifen and the groups stopping tamoxifen or never receiving the drug. Relapse-free survival was superior with increasing duration of exposure to tamoxifen, but this observation can only be considered preliminary due to the small number of patients involved and the study design. The clinical effects observed and the failure to demonstrate the development of a host-metabolic tolerance to tamoxifen provides a rational basis for developing a clinical trial to continue adjuvant tamoxifen therapy for periods in excess of four years after chemotherapy.