Dietary soy consumption has been associated with decreased breast cancer risk in demographic and observational studies in women, and the protective effects appear to be stronger when soy is consumed earlier in life. Rodent studies have demonstrated profound protective effects for animals exposed early in life to soy isoflavones. Our data in the postmenopausal monkey model clearly show antiproliferative effects of soy consumption on the breast, and we have also observed that soy consumption reduces estrogen exposure of the breast. We have demonstrated the predictive value of the monkey model for breast cancer risk in the postmenopausal setting, and we believe that the model is particularly applicable to studies of pubertal breast development, which is difficult to study in human patients. We hypothesize that dietary soy consumption during puberty reduces breast proliferation, induces breast differentiation, and reduces hormonal exposure to the developing breast; such an effect would explain the observed lower risk of breast cancer in women and animals exposed to soy diets early in life. To test this hypothesis, we propose to randomize 40 pre-pubertal female cynomolgus monkeys to receive either a high-soy diet (modeling a soy-supplemented diet) or no dietary soy (modeling a typical North American diet), and to follow them longitudinally through the course of menarche and pubertal breast development by repeated sampling via breast biopsies and serum collection.
Our specific aims are: 1) to determine breast tissue responses to soy consumption during puberty; 2) to determine the effects of dietary soy on ovarian hormones during menarche and menstrual cycling; 3) to determine intratissue estrogens and the enzymes that regulate local estrogen production in the breast; and 4) to explore patterns of gene expression in mammary epithelium which may be modulated by soy consumption. The proposed work will provide a unique view of an otherwise inaccessible period of breast development in a primate model with high genetic and physiologic similarity to human beings.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT000639-08
Application #
7420907
Study Section
Chemo/Dietary Prevention Study Section (CDP)
Program Officer
Sorkin, Barbara C
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
8
Fiscal Year
2008
Total Cost
$575,666
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Pathology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Dewi, Fitriya N; Wood, Charles E; Willson, Cynthia J et al. (2016) Effects of Pubertal Exposure to Dietary Soy on Estrogen Receptor Activity in the Breast of Cynomolgus Macaques. Cancer Prev Res (Phila) 9:385-95
Dewi, Fitriya N; Wood, Charles E; Lees, Cynthia J et al. (2013) Dietary soy effects on mammary gland development during the pubertal transition in nonhuman primates. Cancer Prev Res (Phila) 6:832-42
Dewi, Fitriya N; Wood, Charles E; Lampe, Johanna W et al. (2012) Endogenous and exogenous equol are antiestrogenic in reproductive tissues of apolipoprotein e-null mice. J Nutr 142:1829-35
Wood, Charles E; Boue, Stephen M; Collins-Burow, Bridgette M et al. (2012) Glyceollin-elicited soy protein consumption induces distinct transcriptional effects as compared to standard soy protein. J Agric Food Chem 60:81-6
Stute, Petra; Sielker, Sonja; Wood, Charles E et al. (2012) Life stage differences in mammary gland gene expression profile in non-human primates. Breast Cancer Res Treat 133:617-34
Cline, J Mark; Wood, Charles E (2009) Estrogen/isoflavone interactions in cynomolgus macaques (Macaca fascicularis). Am J Primatol 71:722-31
Scott, Latanya M; Xu, Xia; Veenstra, Timothy D et al. (2008) Past oral contraceptive use and current dietary soy isoflavones influence estrogen metabolism in postmenopausal monkeys (Macaca fascicularis). Cancer Epidemiol Biomarkers Prev 17:2594-602
Scott, L M; Durant, P; Leone-Kabler, S et al. (2008) Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes. J Steroid Biochem Mol Biol 112:179-85
Weinbauer, Gerhard F; Niehoff, Marc; Niehaus, Michael et al. (2008) Physiology and Endocrinology of the Ovarian Cycle in Macaques. Toxicol Pathol 36:7S-23S
Wood, Charles E; Hester, Joy M; Cline, J Mark (2007) Mammary gland development in early pubertal female macaques. Toxicol Pathol 35:795-805

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