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Sir Alexander Haddow discovered the first chemical therapy to treat cancer [1]. Based on Paul Ehrlich’s pioneering work that resulted in chemical therapy or chemotherapy to treat bacterial infections [2], Haddow investigated the therapeutic potential of numerous polycyclic hydrocarbons to cause tumour regression in experimental animals. Some compounds were effective, but the fact that they were known carcinogens prohibited further exploration in humans. Nevertheless, the triphenylethylene-based oestrogens [3] have a structural similarity to polycyclic hydrocarbons and they were also observed to cause tumour regression in animals. This was the translational basis of Haddow’s landmark clinical experiments to evaluate the efficacy of high-dose oestrogen on the growth of breast and prostate cancer. Responses were noted but Haddow later commented [4] in 1970 during the inaugural David A Karnofsky lecture that, ‘The extraordinary extent of tumour regression observed in perhaps 1% of postmenopausal cases has always been regarded as of major theoretical importance and it is a matter of some disappointment that so much of the underlying mechanisms continue to elude us.’ 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 antioestrogen activity. The compound, MER25 or ethamoxy

By looking back we can see the way forward: enhancing the gains achieved with antihormone therapy