A prospective study of cancer-related fatigue in women undergoing radiotherapy for breast cancer.

110 Background: To investigate potential risk factors for cancer-related fatigue in women with breast cancer undergoing whole-breast radiotherapy (RT), we assessed the contribution of chemotherapy (CTX), RT-induced epidermal thickening, and inflammatory mediators to post RT fatigue. Methods: Following lumpectomy, 30 women received whole breast RT (50 Gy plus a 10 Gy boost). Prior to RT, at week 6 of RT, and 6 weeks post RT, subjects completed a validated questionnaire assessing fatigue (Multidimensional Fatigue Inventory [MFI-20]). At the above visits, patients underwent blood sampling for inflammatory mediators. In addition, breast epidermal thickness was measured using ultrasound tissue characterization. Results: Fatigue scores in the sample as a whole did not increase during RT. Independent multivariate analyses of clinical and demographic factors revealed that prior CTX (p<.001) and age <50 (p=.03) were significant predictors of higher post RT fatigue scores. Before, during, and after RT, CTX-treated patients had significantly higher mean fatigue scores than non-CTX-treated subjects. For example, mean MFI scores post RT in patients previously treated with CTX (n=15) were 28 points higher than patients not treated with CTX (mean 61 vs. 33, p<.001), with a clinically meaningful difference being 10 points. Race, cancer stage, and epidermal thickening (defined as a 50% increase over baseline during or after RT, n=17) did not predict higher post RT fatigue scores. Of the inflammatory mediators, plasma IL-6 prior to RT was the strongest predictor of post RT fatigue (p=.02). In addition, plasma IL-6 concentrations prior to RT were significantly higher in patients who received CTX versus those who did not (mean 5.0 vs. 2.5, p=.01). IL-6 prior to RT was also significantly correlated with RT-induced epidermal thickening (p=.04). Conclusions: Our study suggests that CTX-induced inflammation, measured by plasma IL-6, is independently associated with the development of fatigue as well as epidermal thickening in women undergoing breast RT. Treatments targeting inflammation before RT may reduce both fatigue and epidermal thickening post RT, particularly in patients who have been previously been treated with CTX.