Plasma Iron Levels at Early Breast Cancer Diagnosis Are Associated With Development of Secondary Metastases: A Single-Center Retrospective Cohort Study

Background: Breast cancer is the most common malignancy in women and the leading cause of cancer-related death. Although most early-stage patients are cured, 20% to 30% develop metastases, significantly reducing survival rates. Recent research highlights the role of iron in cancer progression, although its full impact on breast cancer metastasis is not yet fully understood.Objectives: The aim of this study is to investigate the association between plasma iron levels at diagnosis of early-stage breast cancer and the risk of developing metastatic disease.Design: Retrospective single-center study.Methods: Patients with stage I to III breast cancer, diagnosed between 2007 and 2017, and with serum iron, transferrin saturation, and ferritin values available within 1.5 months before or after diagnosis were included. Cox proportional hazard models were applied to determine the association between iron levels and risk of metastasis.Results: In total, 1113 patients were included, 10% of them developed distant metastasis over a median follow-up period of 7 years. In multivariable analysis adjusting for age, stage, and subtype, transferrin saturation and serum iron were significantly associated with an increased risk of breast cancer metastasis. For each 10% increment of transferrin saturation at baseline, there was a 19% increase in metastatic risk (hazard ratio [HR] = 1.19; 95% confidence interval [CI] = [1.02-1.38]). Similarly, a serum iron increment of 10 mu g/dL led to a 6% increase in risk (HR = 1.06; 95% CI = [1.01-1.12]). Ferritin was found not to be associated with metastatic risk (HR = 0.99; 95% CI = [0.98, 1.01]). There was no significant association with metastatic site or breast cancer subtype when adjusting for age and stage.Conclusion: Elevated transferrin saturation and serum iron at early breast cancer diagnosis are associated with increased risk for metastatic disease but not with location of metastases or breast cancer subtype. Further research is needed to understand the underlying mechanisms and to explore the potential of iron-targeted therapies.