Role of Cytokines in Breast Cancer: A Systematic Review and Meta-Analysis
Sebastian Ciurescu, Victor Bogdan Buciu, Denis Mihai Șerban, Florina Borozan, Larisa Tomescu, Ionuț Marcel Cobec, Diana Gabriela Ilaș, Ioan Sas
Abstract
Background/Objectives: Cytokines play a fundamental role in the tumor microenvironment, influencing breast cancer progression, metastasis, and therapeutic resistance. The objective of this systematic review and meta-analysis was to evaluate the prognostic impact and therapeutic relevance of key cytokines in breast cancer, based on human studies published between 2015 and 2025. Methods: We systematically searched PubMed, Web of Science, and Scopus for eligible studies reporting on cytokine expression and clinical outcomes in breast cancer. Inclusion criteria were based on the PRISMA framework, focusing on human cohorts and excluding in vitro or animal models. Data were extracted on cytokine types, measurement methods, patient population, and outcomes. Meta-analyses were performed using random-effects models for cytokines with sufficient data, notably IL-6 and TNF-α. Results: Twenty-three studies were included. Elevated IL-6 was consistently associated with poor overall survival (pooled HR = 2.25, 95% CI 1.83–2.76), while high TNF-α levels showed a trend toward worse outcomes but without statistical significance. IL-1β, IL-8, and IL-10 were also linked to increased metastasis and reduced response to therapy. Immunosuppressive cytokines such as IL-10 and TGF-β facilitated tumor immune evasion, while IL-17 promoted inflammation and angiogenesis. Cytokines such as IL-12 and IFN-γ were associated with improved immune responses and a favorable prognosis. Conclusions: Cytokines are central mediators of breast cancer progression and immune regulation. Elevated levels of pro-inflammatory and immunosuppressive cytokines correlate with poor outcomes and may serve as prognostic biomarkers and therapeutic targets. Their integration into personalized treatment strategies holds significant clinical potential but requires further prospective validation and biomarker standardization.