9122 Background: We prospectively evaluated risk factors for persistent cancer-related fatigue in women with breast cancer undergoing lumpectomy with or without chemotherapy (CTX) prior to whole breast radiotherapy (XRT). We assessed the potential role of inflammatory mediators, demographic characteristics, and treatment history including CTX. Methods: Following lumpectomy, 60 women received a definitive course of whole breast XRT (50 Gy plus a 10 Gy boost). Prior to XRT, at week 6 of XRT, and 6 weeks post XRT, subjects completed the Multidimensional Fatigue Inventory (MFI) and underwent blood draws for inflammatory mediators (protein and mRNA). Results: Independent multivariate analyses of clinical and demographic factors revealed that CTX (p<.001) , given neoadjuvantly or adjuvantly, and age <50 (p=.03) were significant predictors of higher fatigue scores post XRT. Mean MFI scores in patients treated with CTX (n=24) were 20 points higher than patients not treated with CTX (p<.001) with a clinically meaningful difference in scores being 10 points on the MFI. Gene ontology analysis of differentially expressed genes indicated increased activation of genes involved in immune and inflammatory responses in fatigued vs. non-fatigued patients (p<.001). Of the inflammatory mediators, plasma IL-6 prior to XRT was the strongest predictor of post XRT fatigue (p=.02). Moreover, plasma IL-6 concentrations prior to XRT were significantly higher in patients who received CTX (mean 4.96 vs. 2.53, p=.01). Patients who received CTX also had significantly higher levels of NF Kappa B DNA binding 6 weeks post XRT (p<.001), and transcription factor binding analysis revealed a greater representation of genes with the NF Kappa B DNA binding motif in fatigued vs. non-fatigued patients (p =.05). Conclusions: Collectively, these data suggest an interaction between CTX and XRT leading to inflammation and fatigue several weeks post XRT. This relationship was independent of whether CTX was given pre or post-operatively. Treatments targeting inflammation before XRT may reduce fatigue post therapy, particularly in patients previously treated with CTX.
Dingchuan tang essential oil inhibits the production of inflammatory mediators via suppressing the IRAK/NF-κB, IRAK/AP-1, and TBK1/IRF3 pathways in lipopolysaccharide-stimulated RAW264.7 cells
