A Cross-Sectional Exploration of Cytokine–Symptom Networks in Breast Cancer Survivors Using Network Analysis

Purpose The purpose of this study is to (a) visualize the symptom–cytokine networks (perceived stress, fatigue, loneliness, perceived cognitive impairment, daytime sleepiness, sleep quality, and 13 cytokines) and (b) explore centrality metrics of symptom–cytokine networks in breast cancer survivors who completed chemotherapy treatment. Methods Cross-sectional analysis of data collected from 66 breast cancer survivors who were on average three years post chemotherapy completion. Perceived stress, fatigue, loneliness, perceived cognitive impairment, daytime sleepiness, and sleep quality were measured with self-report instruments, and a panel of 13 cytokines was measured from serum using multiplex assays. Symptoms and cytokines were simultaneously evaluated with correlations, network analysis, and community analysis. Results Network analysis revealed the nodes with the greatest degree and closeness were interleukin-2, granulocyte-macrophage colony-stimulating factor, interleukin-13, and perceived cognitive impairment. Node betweenness was highest for perceived cognitive impairment and interleukin-2. Community analysis revealed two separate communities of nodes within the network (symptoms and the cytokines). Several edges connected the two communities including perceived cognitive impairment, stress, fatigue, depression, interleukin-2, granulocyte-macrophage colony-stimulating factor, interleukin-8, interleukin-13, and interleukin-10. Partial correlation analyses revealed significant negative relationships between interleukin-2 and fatigue, loneliness, stress, and perceived cognitive impairment (rs = −.27 to −.37, ps