Endocrine Abstracts

The balance of androgen and estrogen hormone activity determines the degree of breast development in males and females. A predominance of androgen action impedes whereas a predominance of estrogen action promotes breast development. This sex hormone antagonism is mechanistically mediated by androgen and estrogen receptors (AR, ER). The alpha form of ER (ERα) is required for normal breast development and is the driving oncogene in the majority of breast cancers. The AR is not required for female breast development but is required for suppression of breast growth in males and modulates post-pubertal breast growth in females. The role of AR in breast cancer is complex, giving rise to ongoing controversies about how best to leverage it as a therapeutic target. In the context of primary ERα positive breast cancer, evidence from previous studies and unpublished data from our laboratory support the concept that AR signalling opposes oncogenic ERα signalling in breast cancer cells and is a viable therapeutic strategy. In contrast, evidence from other studies indicate that AR signalling facilitates ERα signalling so that AR antagonism would also be a viable therapeutic strategy. Similar contradictory findings are present in the arena of endocrine-resistant breast cancers. Currently, both therapeutic strategies (AR agonism and antagonism) are being tested in clinical trials of ERα-positive breast cancer. In this talk, I will present data describing the interaction between ERα and AR on chromatin and its functional consequences in terms of gene regulation and cell cycle control in different models of ERα positive breast cancer, with view to explaining some of the controversies about AR signalling in this form of disease.

DOI: 10.1530/endoabs.54.IS2