Trace element imbalances in selenium and mercury in relation to mammographic density and breast cancer progression: a case‒control study

Breast cancer remains the most prevalent malignancy among women worldwide. Emerging evidence suggests that trace elements, particularly selenium (Se) and mercury (Hg), may contribute to breast cancer pathogenesis. This study aimed to evaluate whether variations in Se and Hg levels in biological matrices are associated with breast cancer stage, related hematological changes and mammographic density. A case-control study was conducted including 285 histologically confirmed breast cancer patients and 215 age-matched controls. Biological samples (scalp hair and blood) were analyzed via atomic absorption spectrometry. Normality was tested (Shapiro-Wilk); parametric (t test, ANOVA) or nonparametric (Mann-Whitney U test, Kruskal-Wallis) tests were applied accordingly, with Tukey/Dunn post hoc corrections. Compared with controls, breast cancer patients presented significantly lower Se levels and higher Hg levels across all stages. For example, the Se concentration in Stage IV hair was 0.25 µg/g (95% CI 0.23-0.27) and that in control hair was 1.59 µg/g (95% CI 1.54-1.64) (t = - 46.2, p < 0.001; Hedges g = - 5.12). The hair Hg concentration was 4.31 µg/g (95% CI 4.24-4.38) vs. 1.19 µg/g (95% CI 1.17-1.21) (t = 84.7, p < 0.001; Hedges g = + 7.05). The blood Se concentration decreased progressively from 220.0 ± 8.2 µg/L in the controls to 51.3 ± 5.8 µg/L in Stage IV (p < 0.001), whereas the blood Hg concentration rose from 0.97 ± 0.05 to 2.94 ± 0.11 µg/L (p < 0.001). Hemoglobin levels also decreased with stage (12.7 ± 1.2 g/dL for controls vs. 5.62 ± 0.38 g/dL for Stage IV patients, p < 0.001). These findings demonstrate a consistent association between low Se and high Hg levels and advanced breast cancer stage and hematological decline. Notably, Se levels fell below the 70 µg/L GPx3 sufficiency threshold, whereas hair Hg levels exceeded the 2 µg/g toxicological guidance threshold, underscoring the clinical relevance of Se. While causal inference is limited, these results suggest that Se and Hg imbalances may serve as biomarkers for progression. These findings should be interpreted in light of international data where Se deficiency is rare, highlighting population-specific risks.