Inflammatory Markers Associated With Radiation-Induced Lung Injury, Metastasis and Mortality After Breast Cancer Treatment.

Purpose: Breast cancer (BC) radiation therapy (RT) prevents local recurrence and improves survival. However, it can induce acute and late effects on organs at risk, such as the lung. In some patients, radiation activates inflammatory markers, which promote inflammation in the lung leading to radiation pneumonitis and fibrosis (RF). Moreover, inflammatory markers may be associated with metastatic disease and survival. This study examines the relationships between inflammatory markers and clinical radiation pneumonitis and RF and explores their potential to predict BC metastasis or overall survival. Methods and Materials: Patients prescribed postoperative BC RT were included in this prospective longitudinal cohort study with assessments before RT (baseline) and after 3, 6, and 12 months and at a long-term follow-up 7 to 12 years after RT. Inflammatory markers from each assessment were analyzed. BC metastasis and overall survival were registered up to 16 years after RT. Results: Monocyte chemoattractant protein 1 at 3 months emerged as a predictor for clinical RF at 12 months. Tumor necrosis factor alpha at baseline and the change in fibroblast growth factor basic, neutrophil lymphocyte ratio, C-reactive protein, and interleukin (IL) 1b (IL-1b) from baseline to 3 months predicted BC metastasis. IL-6 at 3 and 12 months, IL-8 at 12 months, and an increase in fibroblast growth factor basic and IL-6 from baseline to 3 months were associated with all-cause mortality. Conclusions: We found monocyte chemoattractant protein 1 linked to radiation-induced lung injury. Inflammatory markers before and after RT were associated with BC metastasis and all-cause mortality. Our findings indicate that prolonged inflammation following RT may be linked with BC metastasis and overall survival. However, further research is needed to understand their signaling pathways and their role in predicting BC outcomes.