Adjuvant therapy with zoledronic acid in patients with breast cancer: a systematic review and meta-analysis

Abstract

Background: The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer.

Materials and methods: We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes.

Results: Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70-1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%.

Conclusion: Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.

Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.

Flowchart diagram of study selection.

Figure 2.

Forest plot for overall survival outcome. Squares represent hazard ratios and size of squares is proportional to the size of the trials. Error bars represent 95% CIs. For all figures, values

Figure 3.

Forest plot for disease-free survival outcome. Squares represent hazard ratios and size of squares is proportional to the size of the trials. Error bars represent 95% CIs. For all figures, values

Figure 4.

Forest plot for fracture rates. Squares represent odds ratios and size of squares is proportional to the size of the trials. Error bars represent 95% CIs. For all figures, values