Does iron have a role in breast cancer?

Abstract

Oestrogen and family history are two of the most important risk factors for breast cancer. However, these risk factors cannot explain the differences in the incidence and recurrence of breast cancer between premenopausal and postmenopausal women. In this paper I propose that, in premenopausal women, an iron deficiency caused by menstruation stabilises hypoxia inducible factor-1alpha, which increases the formation of vascular endothelial growth factor. This mechanism results in premenopausal women being more susceptible to angiogenesis and, consequently, leads to a high recurrence of breast cancer. Conversely, increased concentrations of iron in postmenopausal women, as a result of menstrual cessation, contribute to a high incidence of breast cancer via oxidative-stress pathways. Although the focus of this Personal View is on iron, this by no means negates the roles of other known risk factors in breast-cancer development. Characterisation of the role of iron in breast cancer could potentially benefit patients by decreasing recurrence and incidence and increasing overall survival.

Figure 1. Lining of the uterus during menstruation

Figure 2. Proposed mechanisms for increased breast-cancer recurrence in premenopausal women (A) and for increased breast-cancer incidence in postmenopausal women (B)

Fe=iron. E2=17β-estradiol. pO₂=partial pressure of oxygen. HIF-α1=hypoxia inducible factor-1α. P4H=prolyl-4-hydroxylase. VEGF=vascular endothelial growth factor. ER=oestrogen receptor. HQ= hydroquinone. SQ=semi-quinone. Q=quinine. SOD=superoxide dismutase. HRT=hormone replacement therapy. ECM=extracellular matrix.