Associations Between Serum Iron Biomarkers and Breast Cancer Tumor Size

Abstract

Abstract Excess iron has been shown to promote tumor growth in animals whereas iron deficiency has been associated with reduced or slowed tumor growth. The objective of this analysis was to estimate the associations between serum iron biomarkers and tumor size at diagnosis and metastatic status in a sample of breast cancer cases from the Sister Study. The analytic sample included 2,494 incident breast cancer cases with information on tumor size and iron biomarkers, including serum iron (mcg/dL), ferritin (mcg/dL), and percent transferrin saturation, measured in serum collected at baseline. We used Spearman rank correlation and linear regression models to assess the associations between one SD changes in serum iron biomarker levels and natural log of tumor size (cm) adjusting for body mass index and age at study entry. We did not find strong associations between any of the three serum iron biomarkers and tumor size. Adjusted regression slopes (95% confidence interval) were −0.016 (−0.048 to 0.016) for serum iron, −0.032 (−0.064 to <0.001) for ferritin, and −0.010 (−0.043 to 0.023) for transferrin saturation. This study did not provide evidence supporting the hypothesis of a positive association between breast cancer tumor size at diagnosis and prediagnostic serum iron levels. Conflicting evidence between this study and previous research in animal models suggests that iron in the human tumor microenvironment may operate independently of circulating iron or body iron stores. Iron has shown protumorigenic activity in animal models, but our data do not support a positive relationship between breast tumor growth and iron status. Significance: Using a large sample of women from a U.S. prospective cohort, we assessed associations between several serum iron measures at baseline and breast cancer tumor size and metastatic status. All estimated associations were close to zero with no evidence to support our hypothesis of higher body iron levels associated with larger tumor size. These results suggest the human tumor microenvironment operates independently of circulating serum iron levels.