Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy

摘要

Abstract Background Cancer-related cognitive impairment (CRCI) is often related to chemotherapy. Increased chronic inflammation is believed to play a key role in the development of CRCI related to chemotherapy but studies assessing this hypothesis specifically in patients receiving chemotherapy are rare. Methods We assessed several cognitive domains using the Cambridge Neuropsychological Test Automated Battery (CANTAB) in twenty-two breast cancer patients currently receiving chemotherapy. We also measured inflammatory cytokine and receptor (MCP-1, TNF-α, sTNFRI, sTNFRII) concentrations in patient sera using Luminex assays. These concentrations were log-transformed to obtain a normal distribution. Associations between log-transformed cytokines and cognition were evaluated using Pearson correlations and linear regression, taking into account relevant covariates. Results Increased concentrations of sTNFRI and sTNFRII were associated with poorer performance on the CANTAB Delayed Matching to Sample (DMS, tests visual memory). Increasing sTNFRI levels were negatively correlated with DMS percent correct (r=?0.47, p=0.029) and DMS percent correct after a 12 second (s) delay (r=?0.65, p=0.001). Increasing levels of sTNFRII negatively correlated with DMS percent correct after 12s delay (r=?0.57, p=0.006). After controlling for relevant demographic (i.e. age, education) and clinical variables (i.e. disease stage, regimen type), we found that increased sTNFRI remained significantly related to decline on the DMS at the 12s delay (p=0.018). Conclusion This preliminary study shows a significant association between higher sTNFRI and lower scores on the short-term visual memory delayed match to sample test in breast cancer patients receiving chemotherapy, supporting the hypothesis that sTNFRI is involved in CRCI. Graphical abstract Display Omitted Highlights ? First study to examine association between inflammation and CRCI during chemotherapy treatment. ? Assessed TNF-α, IL-6, IL-8, sTNFR1, sTNFR2, and IL6R in relation to multiple cognitive domains. ? Increasing sTNFRI concentrations are associated with worse short-term visual memory. ? This association remained after adjustment for age, education, stage, & anthracycline exposure.