Association between inflammatory biomarkers and depressive symptoms in breast cancer: a systematic review.

Breast cancer is one of the most prevalent cancers among women and is frequently accompanied by depressive symptoms. Although the underlying mechanisms remain unclear, inflammation and stress-related biological pathways have been proposed as potential contributors. This systematic review examined the association between inflammatory and stress biomarkers and depressive symptoms in breast cancer patients. A systematic review was conducted in accordance with PRISMA guidelines and registered with PROSPERO (CRD42025632366). PubMed and Web of Science databases were searched, yielding 24 eligible studies. Biomarkers assessed included interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and cortisol. Of nine cross-sectional studies, six reported higher IL-6 levels in association with depressive symptoms, while three found no association. Among nine longitudinal studies, three reported increased IL-6 alongside depression, one found elevated IL-6 without changes in depressive symptoms, four reported no changes in either measure, and one observed persistent depressive symptoms without changes in IL-6. For TNF-α, two of six cross-sectional studies reported elevated levels with depression, whereas the remaining cross-sectional studies and both longitudinal studies found no associations. For CRP, one of two cross-sectional studies reported higher levels in depressed patients. Among eight longitudinal studies, four reported increased CRP with worsening depressive symptoms, two observed elevated CRP without changes in depression, and two reported no changes. For cortisol, only two studies found elevated levels in depressed patients. Overall, the evidence linking inflammatory and stress biomarkers to depressive symptoms in breast cancer patients is inconsistent and does not support a clear or robust association. Heterogeneity in study design, control groups, depression assessment tools, biomarker measurement methods, cancer treatments, and medication use likely contributes to these mixed findings. Future research should prioritise standardised methodologies and large-scale longitudinal designs to clarify the biological mechanisms underlying depression in breast cancer populations.