Fig. 1.

Overview of the steroidogenic pathways thought to be functional in the breast. The classical steroid receptors thought to govern breast cancer prognosis are the oestrogen receptor alpha (ERα) and the Progesterone Receptor (PR). In addition to these the Human Epidermal Growth Factor Receptor 2 (HER2)is also part of the classical panel used to asses breast cancers. This figure demonstrate the extended endocrine environment of the breast with pathways considered in this paper in black, and additional important and potential pathways not studied in grey. This figure is not intended to be a comprehensive diagram of all possible intracrine pathways present in the breast but a guide to the reader of this paper to help orientate them to the significance of the various proteins examined. Circulating precursors such as DHEA-S and E1-S are found in high concentrations in the circulation as are smaller levels of more active steroids such as oestrone (E1), estradiol (E2), Androstenedione (A) and testosterone and cortisol (not shown). Through a series of enzymatic conversions these steroids can be modulated to have greater or lesser activity on a variety of nuclear receptors such as the androgen receptor (AR), oestrogen receptor beta (ERβ) and glucocorticoid receptor (GR) in addition to the classical hormone receptors. Beyond the actions of nuclear receptors the role of cofactors such as FOXA1 and their interactions with hormone receptors are thought to be central to understanding this complex network of interactions