Cytokines, Fatigue, and Cutaneous Erythema in Early Stage Breast Cancer Patients Receiving Adjuvant Radiation Therapy

Abstract

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1β, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1β, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Inflammatory pathway genes associated with inter-individual variability in the trajectories of morning and evening fatigue in patients receiving chemotherapy

“…To date, results are inconclusive, with some studies finding positive associations between fatigue severity and circulating levels of TNF-α [20, 21] and IL-6 [18, 20, 22–29] and others finding no associations with TNF-α[18, 22, 30–33], IL-6 [30, 34–38], and IL-4 [25, 36, 38]. These inconsistent results may be related to the challenges associated with the measurement of serum cytokines, as well as circadian variations in cytokine levels [39].…”

Psychotropic drugs for the management of cancer-related fatigue: a systematic review and meta-analysis

“…CRF is a multidimensional syndrome caused by a number of physical and psychosocial mechanisms, including tumour by‐products (De Sanctis et al . ; Zhang et al . ), cytokine‐causing cachexia, muscle loss or deconditioning.…”

“…The overall prevalence of CRF is estimated to be between 60% and 90% in cancer survivors with ongoing disease (Cella et al 2001;Bruera & Yennurajalingam 2010;Berger et al 2012). CRF is a multidimensional syndrome caused by a number of physical and psychosocial mechanisms, including tumour by-products (De Sanctis et al 2014;Zhang et al 2014), cytokine-causing cachexia, muscle loss or deconditioning. In addition, opioids and other drugs may contribute to fatigue by causing neurocognitive changes and hypogonadism (Huang et al 2010;Saligan & Kim 2012).…”

Breast‐related stereotype threat contributes to a symptom cluster in women with breast cancer

“…, De Sanctis et al . ). Based on the previous findings and our findings, we speculate that BRST might aggravate the symptom cluster by increasing the inflammatory reaction of patients with breast cancer.…”

“…, De Sanctis et al . ) in patients with breast cancer. Second, stereotype threat triggers a series of negative thoughts, negative appraisal and negative emotions in the participants that could lead to working memory depletion.…”