Adjuvant Zoledronic Acid Therapy For Patients With Early Stage Breast Cancer: An Updated Systematic Review And Meta-analysis

BackgroundZoledronic acid is a potent inhibitor of osteoclast-mediated boneresorption and has been widely used in bone metastasis malignancies andpostmenopausal osteoporosis as a preventive therapy against skeletal relatedevents. The purpose of this study was to evaluate the clinical outcome ofzoledronic acid as an adjuvant therapy for patients with early stage breastcancer.Patients and methodsEntries in the PubMed and EMBASE databases up to12July2013were systematically reviewed. Online abstracts from the proceedings of theAnnual Meetings of the American Society of Clinical Oncology (ASCO)(1992–2013) and the San Antonio Breast Cancer Symposium (SABCS)(2004–2013) were also reviewed. Primary endpoints included overallsurvival (OS) and disease-free survival (DFS), while secondary endpointsincluded bone metastasis-free survival (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR).ResultsA total of eight studies including3,866subjects and3,864controls metour search criteria and were evaluated. The use of zoledronic acid was foundto improve OS (relative risk (RR),0.88;95%confidence interval (CI),0.77–1.01; p-value=0.06) and DMFS (RR,0.77;95%CI,0.60–1.00;p-value=0.05). Furthermore, statistically significant benefits wereassociated with BMFS (RR,0.81;95%CI,0.66–0.99; p-value=0.04) andFFRs (RR,0.75;95%CI,0.61–0.92; p-value=0.007). In contrast, there wasno significant difference in DFS with the application of zoledronic acid (RR,0.88;95%CI,0.72–1.09; p-value=0.24). Sensitivity analysis furtheridentified the improvement of5-year OS for the adjuvant zoledronic acidtherapy in early stage breast cancer patients (RR,0.86;95%CI,0.75–0.99;p-value=0.03), while a borderline statistically significant benefit wasobserved for5-year DFS (RR,0.90;95%CI,0.81–1.00; p-value=0.06).ConclusionZoledronic acid as an adjuvant therapy appears to improve the5-yearOS rate for early stage breast cancer patients, and was associated with aprotective effect for the bone metastases and fractures. However, furtherresearch is needed to confirm our findings, and sub-group analysesaccording to menopause status or hormone status may provide furtherinsight.