Cytokines and Brain-Derived Neurotrophic Factor as Biomarkers of Cognitive Impairment Related to Breast Cancer and Its Treatments: A Systematic Review

细胞因子和脑源性神经营养因子作为乳腺癌及其治疗相关认知障碍的生物标志物:系统评价

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Abstract

Breast cancer is a globally prevalent oncological disease whose treatments, while improving survival rates, often lead to adverse cognitive effects. Brain-derived neurotrophic factor (BDNF) and cytokines, key mediators of the inflammatory response, may play a significant role in these cognitive alterations. This systematic review (osf.io/vk37x) addresses the use of BDNF and cytokines as biomarkers of cognitive impairment in breast cancer animal models. A comprehensive literature search was conducted across the following databases: Web of Science, Scopus, ScienceDirect, PubMed, and Medline. Keywords used were: ("breast cancer" AND "cognitive impairment" AND ("brain derived neurotrophic factor" OR "cytokines"). A total of 9876 articles were identified, of which 17 studies met the inclusion criteria. For quality assessment the SYRCLE's tool for assessing Risk of Bias was used. Neuroinflammatory and systemic inflammatory responses, particularly increases in pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and reductions in hippocampal BDNF, are consistently linked to breast cancer and chemotherapy-induced cognitive impairment in animal models. Several interventions normalized these biomarkers and improved cognitive performance after chemotherapy. Anti-inflammatory cytokines (IL-10 or IL-4) were measured in fewer studies and recent research suggests that they could serve as potential protective biomarkers. BDNF, pro- and anti-inflammatory cytokines may represent candidate biomarkers for cancer-related cognitive impairment.

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