Finally, to determine whether DKK1 levels correlate with tumor progression and immune suppression in breast cancer patients, we analyzed DKK1 plasma levels and the activation status of NK cells in the blood of 15 patients with stage IV, HER−, ER+ breast cancer and skeletal disease, at time of diagnosis and after 15 to 18 months of standard-of-care endocrine therapy-based regimens with denosumab as antiresorptive therapy. This evidence concerns the gene ESR1 and bone disorder.