Serum Ferritin and Iron-Related Biomarkers in Relation to Breast Cancer Risk by Menopausal Status: A Prospective Cohort Study

Abstract Background: Iron metabolism may influence breast cancer development; however, links between iron-related biomarkers and breast cancer remain inconclusive. Given differences in iron status by menopausal status, we examined associations of ferritin and other iron biomarkers with breast cancer incidence, stratified by menopausal status, in a Korean screening cohort. Methods: This cohort study included 140,747 Korean women screened for breast cancer from 2011 to 2020. Iron-related markers, including serum ferritin, iron, total iron-binding capacity, and transferrin saturation, were measured. Breast cancer incidence until December 2022 was tracked through the National Cancer Registry. Cox regression estimated HRs with 95% confidence intervals (CI). Results: During a median follow-up of 6.7 years (IQR, 4.9–8.7 years), 1,437 incident cases of breast cancer were identified. Serum ferritin levels were associated with decreased risk of breast cancer in premenopausal, but not postmenopausal, women. The adjusted HR for breast cancer in the highest versus lowest ferritin quartile was 0.76 (95% CI, 0.64–0.89) in premenopausal and 0.87 (95% CI, 0.58–1.29) in postmenopausal women. These findings were consistent for invasive cancer and ductal carcinoma in situ. Other iron-related markers were not significantly associated with breast cancer risk in either group, though serum iron and transferrin saturation showed nonsignificant positive trends in postmenopausal women. Conclusions: An inverse association between serum ferritin levels and breast cancer risk was observed in premenopausal women, with a similar but nonsignificant trend in postmenopausal women. Impact: These findings suggest iron metabolism’s role in breast cancer development and distinct iron-related mechanisms by menopausal status.