Abstract PS2-08-29: Plasma hepcidin as a prognostic biomarker in obese and non-obese patients with early breast cancer (BC): a pooled analysis of two prospective cohort studies

Abstract Background: BC is one of the leading causes of cancer death among women globally, with obesity recognized as a risk factor for adverse clinical outcomes. Chronic inflammation and metabolic dysregulation, often observed in obese individuals, are hypothesized to drive this risk. The potential prognostic significance of the peptide hormone hepcidin, which is a well-known marker of inflammation and iron dysregulation, is therefore of interest in patients with BC. Methods: We performed a pooled analysis of individual patient data within two prospective cohort studies, the “Canadian” (n=518; Jerzak et al, 2020) and “French” (n=144; Durigova et al., 2013) cohorts. Plasma hepcidin levels were measured postoperatively and prior to systemic therapy initiation using the same gold-standard and commercially available ELISA assay (La Jolla, California). Distant disease-free survival (DDFS) was defined as the time between BC diagnosis and first distant recurrence. Overall survival (OS) time was defined as time between BC diagnosis and death from any cause.Cox regression models were fitted using both data sets, treating hepcidin as a continuous variable and with a hepcidin-by-BMI interaction (BMI dichotomized at 30). Cohort-specific ‘beta’ coefficients and standard errors (SE) from each survival model were combined meta-analytically using a random effect model (using the R package ‘metafor’), with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs). HRs are expressed as the hazard at the 75th vs the 25th percentile of the hepcidin distribution in the combined datasets: P25=11.6, P75=31.3 ng/ml. Results: In total, 622 patients were included. At BC diagnosis, 46% were age ≥50, 41% were post-menopausal and 16% were obese (BMI ≥30). Most patients had T1 (57%) or T2 (32%) tumors and 66% had N0/N1mi disease; 75% of BCs were hormone receptor positive in the pooled population and 22% were HER2+ in the French cohort. HER2 status in the Canadian cohort is unknown. Over a median follow-up of 11.6 (95% CI 11.5-11.8) years, 145 patients (22%) experienced a distant relapse and 139 (21%) died.In our pooled analysis of obese BC patients, a significant prognostic interaction between hepcidin levels and obesity was observed. Specifically, among obese women (BMI ≥ 30), elevated plasma hepcidin was significantly associated with shorter DDFS (adjusted HR 2.23; 95% CI 1.23-4.07) and shorter OS (adjusted HR 1.87; 95% CI 1.03-3.39). Conversely, no statistically significant associations were identified among non-obese women (BMI <30) for either DDFS (HR 0.84; 95% CI 0.58-1.22) or OS (HR 1.00; 95% CI 0.72-1.38). Conclusion: Higher plasma hepcidin is independently linked to shorter DDFS and OS in obese, but not non-obese, women with early stage BC. Underlying mechanisms warrant further study. Citation Format: E. A. Cescon, P. J. Goodwin, W. Jacot, A. Bobrie, S. Thezenas, T. Ganz, E. Nemeth, A. E. Lohmann, M. Ennis, K. J. Jerzak. Plasma hepcidin as a prognostic biomarker in obese and non-obese patients with early breast cancer (BC): a pooled analysis of two prospective cohort studies [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-08-29.