A phase 3 study (D-CARE) was conducted that combined a human blocking monoclonal antibody against the receptor for RANKL (denosumab) with standard-of-care adjuvant or neoadjuvant systemic therapy and locoregional treatments; nevertheless, it did not improve disease-related outcomes for women with high-risk early breast cancer [121]. This evidence concerns the gene TNFSF11 and breast carcinoma.