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Acquired Resistance to Tamoxifen: Back to the Beginning

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Tamoxifen

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

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Abstract

The clinical acceptance and validation of the therapeutic strategy of long-term adjuvant tamoxifen treatment mandated an examination of acquired drug resistance under laboratory conditions. The first model in vivo of acquired resistance of ER-positive breast cancer cells transplanted into immune deficient mice demonstrated tamoxifen-stimulated tumor growth after about 2 years of continuous treatment. When tamoxifen was stopped, tumors also grew with physiologic estradiol. The model showed that no estrogen (similar to the use of aromatase inhibitors) or a pure antiestrogen to destroy ER (fulvestrant) presaged this therapeutic approach in clinical trials a decade later. However, the long-term retransplantation of breast tumors with acquired tamoxifen resistance for at least 5 years demonstrated a vulnerability of these tumors. Tamoxifen-stimulated tumor growth but physiologic estrogen now caused tumor regression and apoptosis. The new biology of estrogen-induced apoptosis now is used to explain the decrease in mortality after adjuvant tamoxifen is stopped in patients and also the value of conjugated equine estrogens to reduce breast cancer incidence in women treated in their 60s.

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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). Acquired Resistance to Tamoxifen: Back to the Beginning. In: Tamoxifen. Milestones in Drug Therapy. Springer, Basel. https://doi.org/10.1007/978-3-0348-0664-0_9

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