Plasma Hepcidin as a Prognostic Biomarker in Obese and Nonobese Patients With Early Breast Cancer: A Pooled Analysis...

To evaluate whether elevated baseline plasma hepcidin is associated with shorter time to distant recurrence (TTDR) and overall survival (OS) in women with obesity who are diagnosed with early-stage breast cancer (BC).

We performed a pooled analysis of individual patient data within two prospective cohort studies, the "Canadian" (n = 518) and "French" (n = 144) cohorts. Plasma hepcidin levels were measured postoperatively and prior to systemic therapy initiation. Cox regression models were fitted to each data set, treating hepcidin as a continuous variable and with a hepcidin-by-body mass index (BMI; kg/m²) interaction (BMI dichotomized at 30). Cohort-specific "beta" coefficients and standard errors from each survival model were combined meta-analytically using a random effect model, with results presented as hazard ratios (HRs) and 95% confidence intervals (CIs).

In total, 662 patients were included; the median age was 48.6 years across both cohorts. Most patients (89%) had T1 or T2 tumors, and approximately two-thirds had lymph node-negative disease (69.9% Canadian; 52.8% French). In total, 16.4% and 16.0% of patients in the Canadian and French cohorts were obese (BMI ≥ 30). In our pooled analysis, elevated plasma hepcidin was significantly associated with shorter TTDR (adjusted HR 2.27; 95% CI, 1.26-4.09) and shorter OS (adjusted HR 1.85; 95% CI, 1.02-3.36) among women with obesity. Conversely, no statistically significant associations were identified among nonobese women for either TTDR or OS.

Higher plasma hepcidin levels are independently associated with a significantly shorter TTDR and OS among patients with early-stage BC who are obese, but not their nonobese counterparts. Biological mechanisms underlying this finding warrant further study.