This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Li, Y. Articles by Brown, P. H. Search for Related Content PubMed PubMed Citation Articles by Li, Y. Articles by Brown, P. H. Related Collections Preclinical Intervention Preclinical Intervention: In Vivo (Animals): Drugs, Nutritional Interventions, Mechanisms Commentary

The Rexinoid LG100268 Prevents the Development of Preinvasive and Invasive Estrogen Receptor–Negative Tumors in MMTV-erbB2 Mice

Authors' Affiliations: ¹ Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine; ² Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and ³ Department of Retinoid Research, Ligand Pharmaceuticals, Inc., San Diego, California

Requests for reprints: Powel H. Brown, Breast Center, Baylor College of Medicine, One Baylor Plaza, MS600, Houston, TX 77030. Phone: 713-798-1609; Fax: 713-798-1642; E-mail: pbrown{at}breastcenter.tmc.edu.

Purpose: To test whether a novel rexinoid, LG100268, prevents the development of preinvasive and invasive estrogen receptor–negative mammary tumorigenesis in MMTV-erbB2 mice.

Experimental Design: For invasive breast cancer prevention, MMTV-erbB2 mice were treated with daily gastric gavage of vehicle, LG100268 (10 mg/kg), or LG100268 (100 mg/kg) for long term starting at 3 months of age. For preinvasive lesion study, mice were treated with daily gastric gavage of vehicle or LG100268 (100 mg/kg) for 4 months.

Results: Long-term treatment with LG100268 significantly prevented invasive mammary tumor development. Median time (age) to tumor development was delayed from 217 days in vehicle group to 357 days in low-dose group. In high-dose group, only 2 of 20 mice developed tumors after 430 days of treatment. Short-term treatment of LG100268 significantly prevented the development of preinvasive mammary lesions including hyperplasia and ductal carcinoma in situ. The cancer prevention effect was associated with reduced expression of Ki67 and cyclin D1 in mammary glands by >80%.

Conclusion: Rexinoid LG100268 is an effective chemopreventive agent in preventing the development of both malignant and premalignant mammary lesions in MMTV-erbB2 mice.

Commentary

Rexinoids and Breast Cancer Prevention

Louise R. Howe
Clin. Cancer Res. 2007 13: 5983-5987. [Full Text] [PDF]

This article has been cited by other articles:

				K. Visvanathan, R. T. Chlebowski, P. Hurley, N. F. Col, M. Ropka, D. Collyar, M. Morrow, C. Runowicz, K. I. Pritchard, K. Hagerty, et al. American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Pharmacologic Interventions Including Tamoxifen, Raloxifene, and Aromatase Inhibition for Breast Cancer Risk Reduction J. Clin. Oncol., July 1, 2009; 27(19): 3235 - 3258. [Abstract] [Full Text] [PDF]

				T. E. Strecker, Q. Shen, Y. Zhang, J. L. Hill, Y. Li, C. Wang, H.-T. Kim, T. M. Gilmer, K. R. Sexton, S. G. Hilsenbeck, et al. Effect of Lapatinib on the Development of Estrogen Receptor-Negative Mammary Tumors in Mice J Natl Cancer Inst, January 21, 2009; 101(2): 107 - 113. [Abstract] [Full Text] [PDF]

				K. Liby, R. Risingsong, D. B. Royce, C. R. Williams, M. M. Yore, T. Honda, G. W. Gribble, W. W. Lamph, N. Vannini, I. Sogno, et al. Prevention and Treatment of Experimental Estrogen Receptor-Negative Mammary Carcinogenesis by the Synthetic Triterpenoid CDDO-Methyl Ester and the Rexinoid LG100268 Clin. Cancer Res., July 15, 2008; 14(14): 4556 - 4563. [Abstract] [Full Text] [PDF]

				L. R. Howe Rexinoids and Breast Cancer Prevention Clin. Cancer Res., October 15, 2007; 13(20): 5983 - 5987. [Full Text] [PDF]