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.
OBJECTIVE
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.


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).


CONCLUSIONS
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.
Klijn
J G
JG
Dr Daniel den Hoed Kliniek and University Hospital, Rotterdam, The Netherlands.
Blamey
R W
RW
Boccardo
F
F
Tominaga
T
T
Duchateau
L
L
Sylvester
R
R
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002064:Buserelin / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D017273:Goserelin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D017697:Premenopause; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D002064:Buserelin