Systematic Review and Meta‐Analysis: Association Between Circulating and Tissue Levels of Selenium and Zinc and Breast Cancer Risk

BACKGROUND: Selenium (Se) and zinc (Zn) are essential micronutrients that play roles in antioxidant defense and the regulation of cell proliferation. Increasing evidence suggests that disturbances in trace element balance may contribute to breast carcinogenesis; however, findings across studies remain inconsistent. OBJECTIVE: To evaluate the association between circulating and tissue Se and Zn levels and breast cancer. METHODS: A systematic review and meta-analysis were conducted according to PRISMA 2020 and MOOSE recommendations. Searches were performed in MedLine, EMBASE, and LILACS from database inception until April 15, 2026. Case-control studies comparing selenium and zinc levels between women with breast cancer and control groups were eligible. Two independent reviewers performed study selection, data extraction, risk-of-bias assessment, and publication bias analysis using Egger's regression test. RESULTS: Thirty case-control studies were included. Most studies (83.3%) were classified as high methodological quality according to the Newcastle-Ottawa Scale. Meta-analyses revealed significantly lower selenium levels in plasma (MD = -12.10 μg/L; 95% CI: -17.54 to -6.65; p < 0.0001), selenium in nails (MD = -0.02 μg/g; 95% CI: -0.04 to -0.01; p = 0.006), and zinc in plasma (MD = -0.33; 95% CI: -0.47 to -0.19; p < 0.00001) in breast cancer patients compared with controls. CONCLUSIONS: The pooled findings indicate an inverse association between breast cancer and selenium levels measured in plasma and nails, as well as plasma zinc concentrations. Nevertheless, interpretation should remain cautious because all included studies had observational designs, with marked heterogeneity and potential residual confounding. Lower circulating selenium and zinc levels, together with reduced selenium concentrations in nails, were associated with breast cancer occurrence. Additional prospective studies are required to clarify causality and determine the clinical significance of these associations.