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Acquired Tamoxifen Resistance: Correlation With Reduced Breast Tumor Levels of Tamoxifen and Isomerization of Trans-4-Hydroxytamoxifen
Abstract
Acquired tamoxifen resistance represents a major cause of treatment failure in breast cancer. We implanted estrogen receptor-positive MCF-7 human breast cancer cells in athymic nude BALB/c mice as a model to study in vivo acquired tamoxifen resistance. After 4-6 months of tumor growth suppression by trans-tamoxifen, tumor progression was observed despite continued tamoxifen administration. Acquired resistance was not due to loss of estrogen receptors, to alterations in serum or tumor estrogen levels, or to changes in tamoxifen or its major metabolites in serum. Tamoxifen-resistant tumors remained estrogen dependent in vivo. However, resistance was also associated with the ability of tamoxifen to stimulate tumor growth. Resistant tumors were characterized by markedly lower intracellular tamoxifen levels and by isomerization of the potent antiestrogenic metabolite trans-4-hydroxy-tamoxifen to the less potent cis isomer. Metabolic tolerance, as manifested by alterations in cellular concentrations of tamoxifen and its metabolites, may thus be one mechanism for acquired tamoxifen resistance in breast cancer.
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Cited by
Cummings, S. R., Eckert, S., Krueger, K. A., Grady, D., Powles, T. J., Cauley, J. A., Norton, L., Nickelsen, T., Bjarnason, N. H., Morrow, M., et al. (1999) · JAMA · doi:10.1001/jama.281.23.2189 · Cited by 1,872
Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa032312 · Cited by 1,795
Goss, P. E., Ingle, J. N., Martino, S., Robert, N. J., Muss, H. B., Piccart, M. J., Castiglione, M., Tu, D., Shepherd, L. E., Pritchard, K. I., et al. (2005) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/dji250 · Cited by 1,118
Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes.
Lavinsky, R. M., Jepsen, K., Heinzel, T., Torchia, J., Mullen, T.-M., Schiff, R., Del-Rio, A. L., Ricote, M., Ngo, S., Gemsch, J., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2920 · Cited by 660
Self-citationMechanisms of tamoxifen resistance
Ring, A., & Dowsett, M. (2004) · Endocrine-Related Cancer · doi:10.1677/erc.1.00776 · Cited by 651
Metadata
- Authors
- Osborne, C. K., Coronado, E., Allred, D. C., Wiebe, V., & DeGregorio, M.
- Venue
- JNCI Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 1991-10-16
- Volume
- 83
- Issue
- 20
- Pages
- 1477-1482
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2009428030
- Cited by
- 235
- References
- 0
- FWCI
- 12.61
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Acquired Tamoxifen Resistance: Correlation With Reduced Breast Tumor Levels of Tamoxifen and Isomerization of Trans-4-Hydroxytamoxifen. https://app.cochat.ai/papers/10.1093/jnci/83.20.1477
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- Osborne, C. K., Coronado, E., Allred, D. C., Wiebe, V., & DeGregorio, M. (1991). Acquired Tamoxifen Resistance: Correlation With Reduced Breast Tumor Levels of Tamoxifen and Isomerization of Trans-4-Hydroxytamoxifen. JNCI Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/83.20.1477
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