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 Liu, B. Articles by Thor, A. Search for Related Content PubMed PubMed Citation Articles by Liu, B. Articles by Thor, A.

Low-Dose Dietary Phytoestrogen Abrogates Tamoxifen-Associated Mammary Tumor Prevention

¹ Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma and ² Evanston Northwestern Healthcare Research Institute, Evanston, Illinois

Requests for reprints: Ann Thor, Department of Pathology, University of Oklahoma Health Sciences Center, 940 Stanton L Young Boulevard, BMSB 451, Oklahoma City, OK 73104. Phone: 405-271-2422; Fax: 405-271-2568; E-mail: ann-thor{at}ouhsc.edu.

Wild-type erbB-2/neu transgenic mice were used to study the interactions between tamoxifen and dietary phytoestrogens (or isoflavones) by dose and form in vivo. Mice were randomized to one of four dietary formulas and implanted with an 8-week continuous-release tamoxifen or placebo pellet at 8 weeks of age. In placebo-treated mice, soy meal diet (but not diets supplemented with low-dose or high-dose isoflavones or a casein diet) resulted in prolongation of tumor latency. In tamoxifen-treated mice fed the soy meal, casein, or high-dose isoflavone enriched diets, the majority (>80%) showed no tumor formation by 60 weeks of age. Of the mice that developed tumors, latency was significantly prolonged. In tamoxifen-treated mice fed the low-dose isoflavone enriched diet, a much higher rate of mammary tumor development (>50%; P < 0.002) and a shorter tumor latency were observed. In vitro studies of human and mouse mammary tumor cell lines confirm that low doses of genistein, co-administered with tamoxifen, promote cell proliferation. This is in contrast to tamoxifen alone or tamoxifen with higher doses of genistein that are growth inhibitory. In summary, low-dose dietary isoflavones abrogated tamoxifen-associated mammary tumor prevention in vivo. These interactions are supported by in vitro data from human and mouse mammary tumor cell lines. These dose-associated interactions likely have relevance to the human use of tamoxifen for prevention or treatment of breast cancer.

Key Words: Breast Cancer • Estrogen • Transgenic Mouse • erbB-2

This article has been cited by other articles:

				B. N. Fink, S. E. Steck, M. S. Wolff, J. A. Britton, G. C. Kabat, M. M. Gaudet, P. E. Abrahamson, P. Bell, J. C. Schroeder, S. L. Teitelbaum, et al. Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island Cancer Epidemiol. Biomarkers Prev., November 1, 2007; 16(11): 2285 - 2292. [Abstract] [Full Text] [PDF]

				C. Duffy, K. Perez, and A. Partridge Implications of Phytoestrogen Intake for Breast Cancer CA Cancer J Clin, September 1, 2007; 57(5): 260 - 277. [Abstract] [Full Text] [PDF]

				A. H. Wu, M. C. Pike, L. D. Williams, D. Spicer, C.-C. Tseng, M. I. Churchwell, and D. R. Doerge Tamoxifen, Soy, and Lifestyle Factors in Asian American Women With Breast Cancer J. Clin. Oncol., July 20, 2007; 25(21): 3024 - 3030. [Abstract] [Full Text] [PDF]

				Y. Su, F. A. Simmen, R. Xiao, and R. C. M. Simmen Expression profiling of rat mammary epithelial cells reveals candidate signaling pathways in dietary protection from mammary tumors Physiol Genomics, June 19, 2007; 30(1): 8 - 16. [Abstract] [Full Text] [PDF]

				Z. Mai, G. L. Blackburn, and J.-R. Zhou Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice Carcinogenesis, June 1, 2007; 28(6): 1217 - 1223. [Abstract] [Full Text] [PDF]

				S. Rice and S. A Whitehead Phytoestrogens and breast cancer -promoters or protectors? Endocr. Relat. Cancer, December 1, 2006; 13(4): 995 - 1015. [Abstract] [Full Text] [PDF]

				J. O. Moore, Y. Wang, W. G. Stebbins, D. Gao, X. Zhou, R. Phelps, M. Lebwohl, and H. Wei Photoprotective effect of isoflavone genistein on ultraviolet B-induced pyrimidine dimer formation and PCNA expression in human reconstituted skin and its implications in dermatology and prevention of cutaneous carcinogenesis Carcinogenesis, August 1, 2006; 27(8): 1627 - 1635. [Abstract] [Full Text] [PDF]

				C.-C. Lin, Y.-L. Tsai, M.-T. Huang, Y.-P. Lu, C.-T. Ho, S.-F. Tseng, and S.-C. Teng Inhibition of estradiol-induced mammary proliferation by dibenzoylmethane through the E2-ER-ERE-dependent pathway Carcinogenesis, January 1, 2006; 27(1): 131 - 136. [Abstract] [Full Text] [PDF]

				P. Thelen, J.-G. Scharf, P. Burfeind, B. Hemmerlein, W. Wuttke, B. Spengler, V. Christoffel, R.-H. Ringert, and D. Seidlova-Wuttke Tectorigenin and other phytochemicals extracted from leopard lily Belamcanda chinensis affect new and established targets for therapies in prostate cancer Carcinogenesis, August 1, 2005; 26(8): 1360 - 1367. [Abstract] [Full Text] [PDF]

				R. T. Chlebowski and G. L. Anderson Progestins and Recurrence in Breast Cancer Survivors J Natl Cancer Inst, April 6, 2005; 97(7): 471 - 472. [Full Text] [PDF]