Katarzyna J Jerzak1, Ana E Lohmann2, Marguerite Ennis3, Elizabeta Nemeth4, Tomas Ganz4, Pamela J Goodwin3. 1. Sunnybrook Health Sciences Centre, Odette Cancer Centre, Department of Medicine, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada. katarzyna.jerzak@sunnybrook.ca. 2. London Regional Cancer Program, Department of Oncology, University of Western Ontario, London, ON, Canada. 3. Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mount Sinai Hospital, Toronto, ON, Canada. 4. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Abstract
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.
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.
Entities:
Keywords:
Biomarker; Breast cancer; Hepcidin; Obesity; Plasma iron
Authors: Lance D Miller; Johanna Smeds; Joshy George; Vinsensius B Vega; Liza Vergara; Alexander Ploner; Yudi Pawitan; Per Hall; Sigrid Klaar; Edison T Liu; Jonas Bergh Journal: Proc Natl Acad Sci U S A Date: 2005-09-02 Impact factor: 11.205
Authors: Elizabeta Nemeth; Erika V Valore; Mary Territo; Gary Schiller; Alan Lichtenstein; Tomas Ganz Journal: Blood Date: 2002-11-14 Impact factor: 22.113
Authors: M B Zimmermann; C Zeder; S Muthayya; P Winichagoon; N Chaouki; I Aeberli; R F Hurrell Journal: Int J Obes (Lond) Date: 2008-04-22 Impact factor: 5.095
Authors: Elizabeta Nemeth; Seth Rivera; Victoria Gabayan; Charlotte Keller; Sarah Taudorf; Bente K Pedersen; Tomas Ganz Journal: J Clin Invest Date: 2004-05 Impact factor: 14.808