Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer

SIMPLE SUMMARY: Although cognitive impairments have been complained about in patients with breast cancer who underwent chemotherapy, recent research has described possible neurocognitive decline prior to the start of chemotherapy and suggested that inflammatory cytokines may also have been involved. However, inconsistencies have been found in correlations of cognitive impairments with cancer, chemotherapy, and peridiagnostic cytokine levels. This cross-sectional study aimed to examine associations of cognitive functions and levels of cytokines in patients with newly- diagnosed breast cancer before chemotherapy, those that were 3 to 9 months after completing chemotherapy, and non-cancer controls, adjusting for baseline intelligence quotient, mood, and fatigue. We found that the performance in semantic association of verbal fluency in patients post chemotherapy might be affected by the status of cancer, IL-13, and anxiety. Our results indicated that verbal fluency and anxiety may be important when considering relevant psychosocial managements or prophylactic interventions for cognitive preservation associated with regulations in cytokines. ABSTRACT: Background: We aimed to investigate the associations of breast cancer (BC) and cancer-related chemotherapies with cytokine levels, and cognitive function. Methods: We evaluated subjective and objective cognitive function in BC patients before chemotherapy and 3~9 months after the completion of chemotherapy. Healthy volunteers without cancer were also compared as control group. Interleukins (IL) 2, 4, 5, 6, 10, 12p70, 13, 17A, 1β, IFNγ, and TNFα were measured. Associations of cancer status, chemotherapy and cytokine levels with subjective and objective cognitive impairments were analyzed using a regression model, adjusting for covariates, including IQ and psychological distress. Results: After adjustment, poorer performance in semantic verbal fluency was found in the post-chemotherapy subgroup compared to controls (p = 0.011, η(2) = 0.070); whereas pre-chemotherapy patients scored higher in subjective cognitive perception. Higher IL-13 was associated with lower semantic verbal fluency in the post-chemotherapy subgroup. Higher IL-10 was associated with better perceived cognitive abilities in the pre-chemotherapy and control groups; while IL-5 and IL-13 were associated with lower perceived cognitive abilities in pre-chemotherapy and control groups. Our findings from mediation analysis further suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Conclusions: Our findings suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Different cytokines and their interactions may have different roles of neuroinflammation or neuroprotection that need further research.