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Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030 [K. W., Y. Z., J. H., J. C., H-T. K., S. K. M., S. G. H., P. H. B.]; Department of Clinical Cancer Prevention, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [X-C. X.]; and Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, California 92121 [W. W. L., R. B.]
Despite the effectiveness of the selective estrogen receptor (ER) modulators in preventing ER-positive breast cancer, chemopreventive agents still need to be developed for the prevention of ER-negative breast cancers. The naturally occurring retinoids are promising agents for the prevention of human cancers but are too toxic for long-term chronic use. We previously demonstrated that the chemopreventive effects of the retinoids could be separated from the toxicity by using an RXR-selective retinoid, LGD1069. The studies described here demonstrate that LGD1069 effectively suppresses ER-negative tumor development in mouse mammary tumor virus-erbB2 transgenic mice with minimal toxicity. These studies suggest that receptor-selective retinoids are promising agents for the prevention of breast cancer and that they may be particularly useful in preventing ER-negative breast cancer.
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