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Prognostic associations of plasma hepcidin in women with early breast cancer

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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Data availability

The datasets generated during and/or analysed during the current study are not publicly available due to privacy or ethical restrictions, but are available from the corresponding author on reasonable request.

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Funding

This study was funded by the Hold’ Em for Life Foundation.

Author information

Authors and Affiliations

  1. Sunnybrook Health Sciences Centre, Odette Cancer Centre, Department of Medicine, University of Toronto, 2075 Bayview Ave, Toronto, ON, M4N 3M5, Canada

    Katarzyna J. Jerzak

  2. London Regional Cancer Program, Department of Oncology, University of Western Ontario, London, ON, Canada

    Ana E. Lohmann

  3. Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mount Sinai Hospital, Toronto, ON, Canada

    Marguerite Ennis & Pamela J. Goodwin

  4. David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Elizabeta Nemeth & Tomas Ganz

Authors
  1. Katarzyna J. Jerzak
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  2. Ana E. Lohmann
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  3. Marguerite Ennis
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  4. Elizabeta Nemeth
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  5. Tomas Ganz
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  6. Pamela J. Goodwin
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Contributions

Conceptualization KJJ, EN, TG, and PJG. Data curation KJJ, AEL, ME, and PJG. Formal analysis KJJ, ME, and PJG. Funding acquisition PJG. Investigation KJJ, AEL, ME, EN, TG, and PJG. Methodology KJJ, AEL, ME, EN, TG, and PJG. Project administration KJJ, EN, TG, and PJG. Resources EN, TG, and PJG. Supervision EN, TG, and PJG. Visualization KJJ, AEL, ME, EN, TG, and PJG. Manuscript writing—original draft KJJ and PJG. Manuscript writing—review and editing KJJ, AEL, ME, EN, TG, and PJG.

Corresponding author

Correspondence to Katarzyna J. Jerzak.

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Conflict of interest

KJJ has served as a Consultant/Speaker for and/or attended Advisory Boards for Amgen, Apobiologix, Eli Lilly, Esai, Genomic Health, Inc., Novartis, Pfizer, Purdue Pharma and Roche; she has also received research funding from Astra Zeneca and Eli Lilly. TG and EN are Scientific Founders and Shareholders of Intrinsic LifeSciences and Silarus Pharma, and Consultants for Protagonist, Ionis and Regeneron. TG is a Consultant for Akebia. EN is a Consultant for Vifor.

Ethical approval

The study has received Research Ethics Board for approval as part of a goal to study obesity and nutritional factors in early breast cancer. It has also received administrative approval by the University of Toronto Research Ethics Board.

Informed consent: Informed consent was obtained from all individual participants included in the study.

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Jerzak, K.J., Lohmann, A.E., Ennis, M. et al. Prognostic associations of plasma hepcidin in women with early breast cancer. Breast Cancer Res Treat 184, 927–935 (2020). https://doi.org/10.1007/s10549-020-05903-z

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  • DOI: https://doi.org/10.1007/s10549-020-05903-z

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