Prognostic associations of plasma hepcidin in women with early breast cancer

Purpose

: Iron is essential to energy metabolism, cell proliferation and DNA synthesis, and sufficient iron availability may be required for tumor growth. The hormone hepcidin is a systemic regulator of iron concentration in plasma. Intra-tumor RNA expression of hepcidin has been linked to shorter metastasis-free survival in women with early breast cancer, but the prognostic implications of this inflammatory marker and iron-regulating plasma peptide in the blood are unknown.

Methods

: Using an ELISA assay, hepcidin was measured in the banked blood of 518 women who were recruited from 1989 to 1996 for a prospective cohort study of diet and lifestyle factors in breast cancer. Blood samples were obtained 4–12 weeks post-operatively, prior to treatment with chemotherapy or tamoxifen.

Results

: Hepcidin was not associated with time to distant breast cancer recurrence (primary outcome) nor time to death from any cause. However, a pre-planned interaction test of body mass index (BMI) was statistically significant (p < 0.01). Among obese women (BMI > 30 kg/m²), higher hepcidin was associated with a shorter time to distant breast cancer recurrence in both uni- and multivariable analyses (adjusted HR 1.84; 95% CI 1.04–3.25). For overall survival, a similar pattern was seen in the univariable model but the effect was diminished in a multivariable analysis. Plasma hepcidin was not associated with high-sensitivity C-reactive protein, but it was significantly associated (r ≥ 0.32) with iron indices, including total iron (p < 0.01), transferrin (p < 0.01) and soluble transferrin receptor (p < 0.01).

Conclusions

: Hepcidin may be associated with poor breast cancer outcome in obese women, however, replication is required. The biologic basis for this prognostic association requires further research.