578eP Hepcidin-mediated iron dysregulation in triple-negative breast cancer: Implications for combination therapy with hepcidin inhibitors

Background: Hepcidin, the master regulator of iron homeostasis, is frequently elevated in cancer, contributing to anemia of chronic disease and potentially supporting tumor growth through iron manipulation.We investigated hepcidin dysregulation in TNBC and its potential as a therapeutic target when combined with chemotherapy.Methods: Serum hepcidin and iron parameters were measured by ELISA and atomic absorption spectrophotometry in 54 TNBC patients and 25 controls.Inflammatory markers (IL-6, TNF-), hemoglobin levels, and transferrin saturation were assessed.The relationship between hepcidin levels, iron sequestration, and clinical outcomes was analyzed.The potential impact of hepcidin inhibition on treatment efficacy was evaluated through correlation with chemotherapy response.Results: Advanced TNBC patients exhibited markedly elevated hepcidin levels (25030 ng/mL vs 3510 ng/mL in controls, p<0.001) with corresponding iron sequestration (serum iron 4510 g/dL vs 11025 g/dL, p<0.001).Hepcidin correlated strongly with IL-6 (r=0.81,p<0.001), indicating inflammation-driven upregulation.High hepcidin levels were associated with severe anemia (Hb <10 g/dL in 78% of advanced cases), reduced chemotherapy tolerance, and inferior treatment response.Patients with hepcidin >200 ng/mL had significantly worse overall survival (median 11 vs 22 months, HR=2.9, p<0.001).Non-advanced TNBC showed moderately elevated hepcidin (8520 ng/mL) without significant iron sequestration.Conclusions: Hepcidin-mediated iron dysregulation represents a significant prognostic factor in advanced TNBC, contributing to anemia and potentially limiting chemotherapy efficacy.Combining hepcidin inhibitors with standard chemotherapy may alleviate cancer-related anemia, improve treatment tolerance, and enhance therapeutic outcomes.Clinical trials evaluating hepcidin-targeting strategies in TNBC are warranted.