Does tumor necrosis factor-alpha (TNF-α) play a role in post-chemotherapy cerebral dysfunction?

• Published in: Brain, behavior, and immunity Vol. 30; no. Suppl; pp. S99 - S108
• Main Authors: Ganz, Patricia A., Bower, J.E., Kwan, L., Castellon, S.A., Silverman, D.H.S., Geist, C., Breen, E.C., Irwin, M.R., Cole, S.W.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15.03.2013
• Subjects: Adult; Allergy and Immunology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Brain - metabolism; Brain imaging; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - drug therapy; Breast Neoplasms - psychology; Breast Neoplasms - therapy; Chemotherapy; Cognition Disorders - blood; Cognition Disorders - chemically induced; Cognition Disorders - diagnosis; Cognitive complaints; Combined Modality Therapy; Cytokines - blood; Executive Function; Female; Humans; Inflammation - blood; Inflammation - psychology; Longitudinal Studies; Memory; Middle Aged; Neuropsychological testing; Neuropsychological Tests; Proinflammatory cytokines; Prospective Studies; Psychiatry; Survivors; TNF-α; Tumor Necrosis Factor-alpha - blood; Verbal Learning; Chemotherapy; Brain imaging; TNF-α; Breast cancer; Cognitive complaints; Proinflammatory cytokines; Neuropsychological testing
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2012.07.015

► sTNF-RII is significantly associated with post-chemotherapy cognitive dysfunction in early stage breast cancer patients evaluated during the year after treatment ended. Post-chemotherapy treated cancer patients frequently report cognitive difficulties. The biology of this phenomenon is poorly understood, with uncertainty about possible direct toxic effects on the brain, secondary effects from systemic inflammation, host factors/genetic predisposition to cognitive complaints, or hormonal changes influencing cognitive function. To elucidate possible mechanisms associated with post-treatment cognitive dysfunction among breast cancer survivors, in 2007 we established a prospective, longitudinal, observational cohort study of early stage breast cancer patients, recruited at the end of initial treatments (primary treatment exposure included surgery, ±radiation, ±chemotherapy), and prior to the initiation of adjuvant endocrine therapy. We assessed cognitive complaints, neuropsychological (NP) test performance, markers of inflammation, and brain imaging at baseline, 6months and 12months after enrollment. In this analysis of data from the first 93 patients enrolled in the cohort study, we focus on the relationship of circulating levels of proinflammatory cytokines to cerebral functioning and chemotherapy exposure. Among the proinflammatory cytokines tested (IL-1ra, sTNF-RII, CRP, and IL-6) at baseline, only sTNF-RII was increased among chemotherapy exposed patients, with a significant decline in the year after treatment (p=0.003). Higher baseline sTNF-RII in chemotherapy patients was significantly associated with increased memory complaints. In chemotherapy exposed patients, the longitudinal decline in sTNF-RII was significantly correlated with fewer memory complaints over 12months (r=−0.34, p=0.04). Higher baseline sTNF-RII was also associated with relatively diminished brain metabolism in the inferior frontal cortex (r=−0.55, p=0.02), as well as relatively increased inferior frontal metabolism after 1year, in chemotherapy-exposed subjects. These preliminary findings suggest that post-chemotherapy increases in TNF-α may be playing an important role in the manifestations of cognitive complaints in breast cancer survivors.