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

PURPOSE: 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).

METHODS

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).

RESULTS

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.

CONCLUSIONS

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.