The strong evidence of denosumab effectiveness in BC patients with BM [32,33], its superiority to zoledronate in terms of median time to first SREs (32.4 months vs. 26.4 months) and subsequent on-study SREs (that were reduced by the anti-RANK-L antibody by 22%, as compared to zoledronate) [32,79] and the preclinical data on RANK/RANK-L role in mammary epithelium proliferation [52,53,54] led to investigate the potential activity of the monoclonal antibody in early BC setting, in terms of disease relapse prevention. This evidence concerns the gene TNFSF11 and breast cancer.