V. Craig Jordan, OBE, PhD, DSc, FMedSci Professor of Breast Medical Oncology
Professor of Molecular and Cellular Oncology University of Texas MD Anderson Cancer Center Houston, Texas

Abstract

“There is, perhaps in everything of any consequence, a secret history which it would be amusing to know, could we have it authentically communicated”
-James Boswell, The Life of Samuel Johnson, LLD

In 1970, the pharmaceutical industry was not interested in developing drugs to treat cancer. In 1970, there was no tamoxifen, raloxifene, or selective estrogen receptor modulators (SERMs). All hopes on the cure for cancer were pinned on combination cytotoxic chemotherapy, because this approach had been remarkably successful for curing childhood leukemia and Hodgkin’s disease. The pharmaceutical industry at the time had been particularly interested in developing new forms of contraception hot on the heels of the enormous success of the oral contraceptive introduced in 1960. However, the group of chemicals called non-steroidal anti-estrogens were found to be perfect “morning after pills”in rats, but did exactly the opposite in women by inducing ovulation. In 1970, Jordan was conducting his PhD research on these failed morning after pills, but by a series of lucky coincidences, he turned his attention to a compound called ICI 46, 474, which became tamoxifen.
Jordan reinvented the strategy of using tamoxifen to treat and prevent breast cancer, and as a result, changed medical practice by introducing the first targeted therapy for cancer shown to save lives. From this work in the 1970’s, Jordan studied the pharmacology of non-steroidal anti-estrogens and by 1980, he had discovered that these compounds switched on or switched off estrogen target tissues around the body. Tamoxifen maintained bone density, decreased circulating cholesterol, but at the same time, blocked estrogen stimulated breast cancer growth. He also discovered that tamoxifen had the potential to increase the risk of endometrial cancer. He conceived the idea that became today the new group of medicines called SERMs. Raloxifene was the result, a medicine that is FDA approved to treat and prevent osteoporosis, but prevents breast cancer at the same time. It does not increase the risk of endometrial cancer. Today, there are 5 FDA approved SERMs: tamoxifen, raloxifene, toremifene, bazedoxifene ,and ospemifene. Millions of women around the world continue to gain benefit either by increased survivorship from breast cancer, or by improved quality of life, reducing the risk of breast cancer, or improving post-menopausal quality of life.

Recommended Reading
Tamoxifen-Pioneering Medicine in Breast Cancer by Philipp Y. Maximov, Russell E. McDaniel and
V. Craig Jordan (2013). Milestones in Drug Therapy Series. Springer Basel AG, Basal, Switzerland,

Estrogen Action, Selective Estrogen Receptor Modulators and Women’s Health: Progress and Promise edited by V. Craig Jordan (2013) Imperial College Press I World Scientific, London