Figure 2.

A trickle to tamoxifen (ICI 46 474). During the 1960s, a number of triphenylethylene derivatives were discovered that were excellent novel post-coital antifertility agents in rats but induced ovulation in subfertile women (clomiphene and tamoxifen) 26. Tamoxifen moved forward as a palliative treatment for metastatic breast cancer, only after being all but abandoned as a commercially viable enterprise. It was then rescued as an orphan drug in 1972 93. Laboratory models informed about possible applications as a long term adjuvant therapy or as a chemopreventive agent 27. Clinical trials demonstrated major survival advantages for women with ER positive breast cancer who received long term (>5 years) tamoxifen therapy and tamoxifen was tested and was the first medicine to be approved for the reduction of breast cancer in high risk women 93