Bisphosphonates and Prevention of the Perimenopausal Breast Cancer Recurrence: A Systematic Review and Meta-Analysis

PURPOSE: Bisphosphonates (BPs) have a powerful effect on reducing bone resorption and improving the survival of patients with breast cancer. We aimed to investigate the impact of BP treatment on the prevention of recurrence, metastasis, and death of breast cancer survivors in the perimenopausal period. METHODS: The search strategy aimed to identify both published and unpublished studies in PubMed, Web of Science, Scopus, Embase, ProQuest, and Google Scholar in March 2021. Two independent reviewers assessed quantitative papers selected for retrieval for methodological validity before being included in the review using standardized critical appraisal instruments from the Joanna Briggs Institute (JBI) Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI). Statistical meta-analysis was performed using Review Manager (RevMan) 5.4 statistical software when the data were homogenous. Meta-analysis was performed by calculating the effect size (hazard ratio; HR) and 95% confidence intervals (CIs). RESULTS: Twenty-one studies were eligible for this systematic review and meta-analysis. The overall The HRs for disease-free survival (DFS) and overall survival (OS) in women who received BPs were 0.89 (95% CI, 0.83–0.97; p = 0.005), and 0.75 (95% CI, 0.63–0.89; p = 0.001), respectively. The results showed that BPs had a significant effect on the prevention of locoregional (HR, 0.64; 95% CI, 0.42–0.97; p = 0.04), bone (95% CI, 0.74–0.95; p ≤ 0.001), and distant metastases (HR, 0.77; 95% CI, 0.62–0.94; p = 0.01). In the subgroup analysis based on study design, the only insignificant HR in the included randomized controlled trials (RCTs) was that of locoregional metastasis. CONCLUSION: Although BPs have a promising effect on DFS, OS, and bone metastasis of perimenopausal women survivors of breast cancer, more RCTs are needed to evaluate their effect on other survivors’ outcomes.