Skip to main content
Top
Published in: Breast Cancer Research and Treatment 3/2020

01-12-2020 | Obesity | Epidemiology

Prognostic associations of plasma hepcidin in women with early breast cancer

Authors: Katarzyna J. Jerzak, Ana E. Lohmann, Marguerite Ennis, Elizabeta Nemeth, Tomas Ganz, Pamela J. Goodwin

Published in: Breast Cancer Research and Treatment | Issue 3/2020

Login to get access

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.
Appendix
Available only for authorised users
Literature
6.
go back to reference Fukuchi K, Tomoyasu S, Watanabe H et al (1995) Iron deprivation results in an increase in p53 expression. Biol Chem Hoppe Seyler 376:627–630CrossRef Fukuchi K, Tomoyasu S, Watanabe H et al (1995) Iron deprivation results in an increase in p53 expression. Biol Chem Hoppe Seyler 376:627–630CrossRef
8.
go back to reference Lucas JJ, Szepesi A, Domenico J et al (1995) Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: selective inhibition of the appearance of the cyclin A-associated component of the p33(cdk2) kinase. Blood 86:2268–2280CrossRef Lucas JJ, Szepesi A, Domenico J et al (1995) Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: selective inhibition of the appearance of the cyclin A-associated component of the p33(cdk2) kinase. Blood 86:2268–2280CrossRef
16.
go back to reference Sørlie T, Sørlie T, Tibshirani R et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423CrossRef Sørlie T, Sørlie T, Tibshirani R et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423CrossRef
32.
go back to reference Gomella LG, Haist SA (2007) Chapter 4. Laboratory diagnosis: chemistry, immunology, serology. In: Clinician’s pocket reference: The Scut Monkey, 11e Gomella LG, Haist SA (2007) Chapter 4. Laboratory diagnosis: chemistry, immunology, serology. In: Clinician’s pocket reference: The Scut Monkey, 11e
Metadata
Title
Prognostic associations of plasma hepcidin in women with early breast cancer
Authors
Katarzyna J. Jerzak
Ana E. Lohmann
Marguerite Ennis
Elizabeta Nemeth
Tomas Ganz
Pamela J. Goodwin
Publication date
01-12-2020
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-020-05903-z

Other articles of this Issue 3/2020

Breast Cancer Research and Treatment 3/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine