Predicting Response to Radiotherapy in Breast Cancer-Induced Bone Pain: Relationship Between Pain and Serum Cytokine Expression Levels After Radiotherapy

INTRODUCTION: Breast cancer is the second leading cause of cancer-associated death in women. Herein, we explored the associations of cytokines, pain, and bone metastasis between patients before and after radiotherapy in breast cancer with bone metastasis. The pain caused by metastasis was effectively relieved by external radiation therapy. However, the underlying mechanisms remain unknown. METHODS AND RESULTS: In this case-controlled study, we enrolled healthy individuals (n = 10) and bone metastatic cancer patients (n = 30). Peripheral venous blood samples were collected from healthy controls, and one week before and after radiotherapy, the peripheral venous blood and clinical characteristics of cancer patients were collected. We analyzed the blood cytokine profile, quality of life (QOL), and pain score of patients pre- and post-radiotherapy to explore the possible causes of pain relief. Both the pain score and QOL significantly improved after radiotherapy. The serum cytokine profiles of patients were significantly different before radiotherapy than after. Meanwhile, only three cytokines differed between post-radiotherapy and healthy controls. We believe radiotherapy stimulated local immune storms in bone tissue and promoted significant changes in cytokines pre- and post-radiotherapy. Therefore, the bone microenvironment of early breast cancer patients with bone metastasis pain can be restored after radiotherapy. Restoring a healthy bone environment can not only relieve the pain but also improve the patient’s QOL. CONCLUSION: Tumor cells can effectively activate immune cells in the bone microenvironment through direct interaction, releasing many factors and promoting bone metastasis. Early local radiotherapy of bone metastases can restore the microenvironment and improve the QOL and prognosis of patients, thereby comprehending a novel target for prevention, treatment, and therapy of bone metastases.