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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

From the Dr Daniel den Hoed Kliniek and University Hospital, Rotterdam, The Netherlands; City Hospital, Nottingham, United Kingdom; Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy; Toyosu Hospital, Showa University School of Medicine, Tokyo, Japan; and European Organization for Research and Treatment of Cancer Data Center, Brussels, Belgium.

Address reprint requests to L. Duchateau, PhD, European Organization for Research and Treatment of Cancer Data Center, Av. E. Mounier 83, Box 11, 1200 Brussels, Belgium; email LDU{at}EORTC.BE

PURPOSE: The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen 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 tamoxifen were identified. Meta-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.

The meta-analysis was independently performed by the Meta-Analysis Unit of the European Organization for Research and Treatment of Cancer Data Center.

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