**5. Current data and use of Denosumab**

Denosumab is a human recombinant monoclonal antibody against RANKL. Inhibition of RANKL leads to reduced maturation of preosteoclasts into osteoclasts, osteoclast survival, and activity. As a result, diminished bone resorption occurs [20].

In the Austrian Breast and Colorectal Cancer Study Group (ABCSG)-18 Study (ClinicalTrials.gov NCT00556374), 3425 postmenopausal women with early luminal breast cancer and aromatase inhibitor therapy were randomized to receive denosumab 60 mg every 6 months or placebo. The primary endpoint was occurrence of clinically relevant fractures. Secondary endpoints included disease-free survival (DFS), bone-metastasis-free survival (BMFS), and overall survival (OS). In the follow-up presented at American Society of Clinical Oncology (ASCO) 2022 with an 8-year follow-up, all clinical endpoints were positive: fractures were 201 in the denosumab and 255 in the placebo arm (HR 0.76, 95% CI 0.63–0.92, p = 0.004). The absolute 9-year DFS difference is 3.5% (79.4% vs. 75.9%, respectively). No new safety signals were presented at the meeting. The authors concluded that denosumab should be considered in routine practice for patients with early hormonal-receptor positive breast cancer [23].
