Endocrine Abstracts

Introduction: While a great degree of focus has recently been placed on identifying novel steroidogenic pathways that are active in cancer development (e.g. Androgen metabolism and Androgen Receptor (AR) Signalling, Glucocorticoid Metabolism and Glucocorticoid receptor (GR) signalling) very few studies have examined these pathways in normal breast samples taken under non-pathological conditions. Furthermore, very few studies have examined the steroid levels in non-pathological breast samples.

Methodology: To address this we examined the immunoreactivity of AR, GR and their related enzymes in forty paraffin embedded-formalin fixed samples taken from mammary reduction surgery. In parallel, we examined the levels of steroids via GC–MS/MS in distal to tumour, histological normal samples, taken during surgery for breast cancer in order to identify the steroids present in these samples and any changes between these and tumour levels of steroids.

Results: AR, 5αR1 and 17βHSD5 as well as GR, 11βHSD1 and 11βHSD2 were apparent in the lobules and ducts of normal breast tissues. In an initial analysis of a subset of the samples, both receptors were associated with their cognate enzymes, although these associations did not reach statistical significance. Most interestingly, GR expression was correlated with that of androgen-altering enzymes (<0.01, 5αR1 R²=0.33 and 17βHSD5 R²=0.56). As BMI is considered a potential risk factor in the development of breast cancer, we tested the correlation between BMI and the level of expression of GR and AR. This analysis showed that a higher BMI correlated with higher expression of AR (P=0.04, R²=0.23). When analysing the levels of steroids present in histological normal, distal to cancer tissues we found that the most abundant sex steroid was DHEA with the following hierarchy of steroids DHEA>Adione>T>E2>DHT, and the two steroids that varied significantly between matched normal and cancer samples were E2 (increased in cancer) and Adione (decreased in cancer) suggesting the importance of localised metabolism of steroids.

Conclusions: Our data suggests the importance of intracrine conversion of steroids in the normal breast and the presence of complete (ligand, enzyme and receptor) significant intracrine pathways. It also suggests some linkage between obesity, a potential risk factor in breast cancer development, and expression of GR and AR in breast cancer tissues.