Combined tamoxifen and luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer: A meta-analysis of four randomized trials

Purpose: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tomoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer. Patients and Methods: Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tomoxifen were identified. Meto-analytic techniques were used to analyze individual patient data from these trials. Results: With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] =0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR =0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio =0.67). Conclusion: The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment. © 2001 by American Society of Clinical Oncology.