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Open Access Highly Accessed Research article

A link between premenopausal iron deficiency and breast cancer malignancy

Jinlong Jian1, Qing Yang1, Yongzhao Shao1, Deborah Axelrod25, Julia Smith35, Baljit Singh45, Stephanie Krauter45, Luis Chiriboga45, Zhaoxu Yang6, Jinqing Li7 and Xi Huang135*

Author Affiliations

1 Department of Environmental Medicine, New York University (NYU), 550 First Avenue, New York, NY 10016, USA

2 Department of Surgery, New York University (NYU), 550 First Avenue, New York, NY 10016, USA

3 Department of Medicine, New York University (NYU), 550 First Avenue, New York, NY 10016, USA

4 Department of Pathology, New York University (NYU), 550 First Avenue, New York, NY 10016, USA

5 Department of Environmental Medicine, NYU Cancer Institute, NYU School of Medicine 550 First Avenue, New York, NY 10016, USA

6 Xijing Hospital, Fourth Military Medical University, Xi’an 710032, P. R.China

7 Tangdu Hospital, Fourth Military Medical University, Xi’an 710032, P. R.China

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BMC Cancer 2013, 13:307  doi:10.1186/1471-2407-13-307

Published: 24 June 2013

Abstract

Background

Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified.

Methods

One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role.

Results

We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002).

Conclusions

Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients.

Keywords:
Iron deficiency; Young breast cancer; Metastasis; Anemia; Epithelial mesenchymal transition; Hypoxia-inducible factors