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The Wisconsin Story in the 1980s: Discovery of Target Site-Specific Estrogen Action

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Tamoxifen

Part of the book series: Milestones in Drug Therapy ((MDT))

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Abstract

The idea that tamoxifen could potentially be employed to prevent breast cancer in populations of women with high risk, naturally mandated an extensive laboratory and clinical investigation of potential toxicological concerns. It was reasoned that if estrogen was necessary to maintain bone density and protect women from coronary heart disease, then an “antiestrogen” might prevent breast cancer but increase the risks of osteoporosis and coronary heart disease. Laboratory results and translation to clinical trial proved the reverse was true, and the new drug group, selective estrogen receptor modulators (SERMs), was discovered. Tamoxifen (and raloxifene) paradoxically prevented bone loss in ovariectomized rats (estrogen-like) but prevented rat mammary carcinogenesis (antiestrogen-like). The same was true in patients with tamoxifen (and raloxifene) maintaining bone density but preventing breast cancer. Additionally, circulating cholesterol decreased (an estrogen-like effect) in patients. However, an estrogen-like effect of tamoxifen that became a concern was the discovery that in the laboratory, tamoxifen prevented breast cancer growth but enhanced the growth of endometrial cancer.

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  1. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA

    Philipp Y. Maximov, Russell E. McDaniel & V. Craig Jordan

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  1. Philipp Y. Maximov
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  2. Russell E. McDaniel
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  3. V. Craig Jordan
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Maximov, P.Y., McDaniel, R.E., Jordan, V.C. (2013). The Wisconsin Story in the 1980s: Discovery of Target Site-Specific Estrogen Action. In: Tamoxifen. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0348-0664-0_5

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