In light of the different roles of the RANKL/RANK pathway in bone metabolism and immune system functions, therapy targeting this axis may not only control primary tumor development such as in the case of breast cancer and reduce bone metastasis which has been demonstrated in clinical trials (152, 153) but also exert a direct anti-tumor effect via regulating local tumor-associated immune responses, as observed in studies using the monoclonal RANKL antibody inhibitor Denosumab (154, 155). This evidence concerns the gene TNFRSF11A and breast carcinoma.