The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis

Context Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. Objective To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. Methods We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). Results In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. Conclusion Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.