Oestrogen suppression—lessons from clinical studies

In few, if any, areas of cancer research has ‘translational research’ played a role such as the one it has played in the development of endocrine therapy. Thus, much of the understanding of the mechanisms of action of different therapies has been achieved by developing novel hypotheses based on clinical observations. Ovarian ablation was developed as an empirical therapy long before characterization of oestrogen disposition or detection of the oestrogen receptor. The first-generation aromatase inhibitor, aminoglutethimide, was implemented as a strategy to achieve a ‘medical adrenalectomy’ and was discovered as an aromatase inhibitor subsequent to clinical observations. Currently, observations such as the lack of cross-resistance between aromatase inhibitors and inactivators and the diverse effects from combined therapy using tamoxifen in concert with hormonal suppression in pre- and post-menopausals are provoking interesting questions for further research.