%0 Journal Article
%T By looking back we can see the way forward: enhancing the gains achieved with antihormone therapy
%A V Craig Jordan
%A Roshani Patel
%A Joan S Lewis-Wambi
%A Ramona F Swaby
%J Breast Cancer Research
%D 2008
%I BioMed Central
%R 10.1186/bcr2176
%X High-dose oestrogen therapy was introduced into clinical care during the 1950s [5] for the treatment of postmenopausal women with metastatic breast cancer. This approach complemented the use of ovarian ablation (using radiation at that time) in premenopausal patients, but the observation that high-dose oestrogen was an effective treatment for one in three elderly postmenopausal breast cancer patients remained a mechanistic paradox until recently [6].Through serendipity, a young endocrinologist, Leonard Lerner at Merrell Dowe Pharmaceuticals in the USA, recognized that a triphenylethanolic compound being tested as a cardiovascular drug had a structure similar to the triphenylethylenes [7]. He asked to test the compound but found that there was no oestrogenic activity in any species tested, only anti-oestrogen activity. The compound, MER25 or ethamoxy-triphetol, was the first nonsteroidal anti-oestrogen [8]. However, it was the fact that nonsteroidal anti-oestrogens were postcoital antifertility agents in rats that drove the structural evolution of triphenylethylene-based oestrogens to become a whole range of novel anti-oestrogenic compounds [9]. Regrettably, the promise of preventing pregnancy was premature because the compounds actually induced ovulation [10]. Also, drug toxicities noted during the 1960s and 1970s retarded any serious consideration of the non-steroidal anti-oestrogens as therapeutic agents for indications such as breast cancer therapy [10]. Only ICI 46,474, the trans isomer of a substituted triphenylethylene [11], took a tenuous path to clinical testing in breast cancer [10,12] and was subsequently kept on life support to be reinvented [13] as a potential targeted therapy for the long-term adjuvant treatment and prevention for oestrogen receptor positive breast cancer.Today, the advance with the clinical implementation of the scientific strategy is profound [14,15], and the practice of oncology has progressed significantly over the past three decade
%U http://breast-cancer-research.com/content/10/S4/S16