The first targeted therapy to treat cancer: the tamoxifen tale

The chance discovery of a new group of medicines called nonsteroidal anti-estrogens opened the door to new opportunities in therapeutics. Ethamoxytriphetol (MER25) was the first. However, based on studies in rats and mice, initial hopes were that nonsteroidal anti-estrogens would be new “morning after pills.” However, the discovery that clomiphene and tamoxifen induced ovulation in subfertile women would produce only a niche market in the 1960s. The treatment of metastatic breast cancer was an obvious choice as endocrine ablative surgery, i.e., oophorectomy, adrenalectomy, or hypophysectomy, was standard of care. Over a decade, in the 1970s, numerous nonsteroidal anti-estrogens were tested, but only tamoxifen went forward for the treatment of all stages of breast cancer, ductal carcinoma in situ, and male breast cancer and the reduction of risk for breast cancer in high-risk pre- and postmenopausal women.