Combined treatment with buserelin and tamoxifen in premenopausal metastatic breast cancer: A randomized study

Background: Surgical or medical castration and antiestrogenic treatment wit h tamoxifen are common endocrine treatments for premenopausal women with br east cancer. However, tamoxifen therapy induces high levels of plasma estra diol, with unknown long-term effects. fn this study, we investigated the ef fect of combining estrogen suppression with the luteinizing hormone-releasi ng hormone agonist buserelin and estradiol receptor blockade with tamoxifen to determine whether the high estradiol levels induced by tamoxifen could be reduced and whether the antitumor effects would be better. Methods: In a three-arm, randomized, prospective trial, from 1988 through 1995, a total of 161 premenopausal patients with advanced breast cancer were randomly ass igned to treatment with buserelin, tamoxifen, or both. Patients with steroi d receptor-negative tumors or with tumors of unknown receptor status who ha d a disease-free interval of less than 2 years were excluded. The median fo llow-up was 7.3 years, during which 76% of the patients died, all of breast cancer. Patient and tumor characteristics were well balanced among treatme nt groups. All P values are from two-sided tests. Results: Combined treatme nt with buserelin and tamoxifen was superior to treatment with buserelin or tamoxifen alone by objective response rate (48%, 34%, and 28% of patients who could be evaluated, respectively; P = .11 [chi(2) test]), median progre ssion-free survival (9.7 months, 6.3 months, and 5.6 months; P = .03), and overall survival (3.7 years, 2.5 years, and 2.9 years; P = .01), Actuarial 5-year survival percentages were 34.2% (95% confidence interval [CI] = 20.4 % - 48.0%), 14.9% (95% CI = 3.9% - 25.9%), and 18.4% (95% CI = 7.0% - 29.8% ), respectively. No differences in antitumor effects were observed between single-agent treatment groups. During combined treatment or treatment with buserelin alone, plasma estradiol levels were suppressed equally; in contra st, during treatment with tamoxifen alone, plasma estradiol levels increase d threefold to fourfold over pretreatment levels. Conclusion: Combined trea tment with buserelin and tamoxifen was more effective and resulted in longe r overall survival than treatment with either drug alone.