Importantly, the immune-modulatory effect of RANK signaling is confirmed in the D-BEYOND (denosumab, a RANK-ligand (RANKL) inhibitor and its Biological Effects in YOuNg premenopausal women Diagnosed with early breast cancer) clinical trial (NCT01864798), a prospective, pre-operative study evaluating denosumab and its biological effects in premenopausal early-stage BC. This evidence concerns the gene TNFSF11 and breast cancer.