To investigate whether the pathological effects of Mstn on bone are predominantly mediated by its local secretion within the bone microenvironment by bone-metastatic tumor cells, rather than through systemic elevation, we performed an additional analysis comparing circulating Mstn levels among three patient groups: those with primary BC tumors only, those with both primary BC tumors and bone metastases, and control patients harboring non-invasive proliferative lesions, including lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). The gene discussed is MSTN; the disease is ductal breast carcinoma in situ.