Adjuvant ovarian function suppression and tamoxifen in premenopausal breast cancer patients: A meta-analysis

Background: The benefit of adding ovarian function suppression (OFS) to tamoxifen in the adjuvant treatment of premenopausal women with breast cancer is uncertain. We conducted a meta-analysis of randomized controlled trials that addressed this question. Methods: Systematic search of PubMed, the web of science, and the meeting library of ASCO, ESMO, and SABCS was conducted using the following keywords: tamoxifen, ovarian suppression, and breast cancer. Eligible studies were those recruiting patients with breast cancer randomized to receive adjuvant tamoxifen and OFS versus tamoxifen alone. Pooled hazard ratio [HR]) for disease-free (DFS) and overall survival (OS) with 95% confidence interval (CI) were calculated using the fixed effect model. Results: We searched a total of 845 records, of which 5 clinical trials, including 7557 patients, were eligible for our analysis. Adding OFS to tamoxifen improved DFS with pooled HR: 0.88 (95% CI: 0.80-0.96, P= 0.004) and OS (pooled HR: 0.87 {95% CI: 0.77-0.98, P= 0.02}) compared to tamoxifen alone. The benefit of the addition of OFS to tamoxifen was mostly observed in patients younger than 40 years where the pooled HRs of DFS was 0.76 (95% CI: 0.63-0.91; P= 0.004), and in those who received adjuvant chemotherapy with pooled HRs of DFS 0.80 (95% CI: 0.65-0.99, P= 0.042). There was an increase in the incidence of all grade musculoskeletal symptoms and high-grade hot flushes with the addition of OFS with risk ratios of 1.12 (95% CI: 1.07-1.17, P< 0.001) and 2.14 (95% CI: 1.01-4.51, P= 0.047) respectively. Conclusion: Our analysis indicates that the addition of OFS to tamoxifen improves DFS and OS. This strategy could be considered in patients in which tamoxifen alone is not deemed sufficient or in case of poor tolerance to OFS with aromatase inhibitors.