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

## TL;DR

This review explores how brain-derived neurotrophic factor and cytokines could serve as biomarkers for cognitive issues in breast cancer and its treatments.

## Contribution

The study systematically reviews animal model evidence linking BDNF and cytokines to cognitive impairment in breast cancer and chemotherapy.

## Key findings

- Increased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and decreased hippocampal BDNF are linked to cognitive impairment in breast cancer animal models.
- Interventions that normalize these biomarkers improve cognitive performance after chemotherapy.
- Anti-inflammatory cytokines like IL-10 or IL-4 may act as protective biomarkers but are less studied.

## 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.