Dietary lignan effects on hormone, growth, and signaling factors in breast tumors

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DESCRIPTION (provided by applicant): Several epidemiologic studies have shown reduced breast cancer risks associated with higher exposure to dietary lignans. Recently, we and others have further shown reduced risks of estrogen receptor (ER) negative breast cancer in women with high versus low dietary intakes, suggesting that the protective effects might be more effective in certain sub-types of cancer. ER status, as well as a number of other tumor characteristics, has been associated with breast cancer prognosis. Although experimental evidence supports the potential for dietary lignans to favorably affect many of these tumor markers, much of the laboratory work has used pharmacologic doses of lignans from flaxseed. Besides the limited data regarding lignan intakes and ER status, an examination of the effect of commonly consumed ranges of dietary lignan intakes on other prognostic and predictive tumor characteristics has not been conducted. Lignans constitute the largest contribution to phytoestrogen intakes among Western populations where soy intake is generally low, and intakes can range widely depending upon which foods are consumed. The wide range of possible intakes is important as experimental evidence suggests that phytoestrogen actions often are concentration dependent, and it is unclear whether amounts consumed via diet produce the same effects as pharmacologic doses available as dietary supplements. Elucidation of the effects of a wide range of phytoestrogen levels is necessary to adequately understand the mechanisms by which lignan intake can affect tumor growth and development. Roswell Park Cancer Institute (RPCI) has developed a core resource for cancer related research. The Data Bank and Biorepository (DBBR) is a comprehensive information and sample bank containing biospecimens and associated clinical and epidemiologic data. The data and biospecimens are donated by RPCI patients who have cancer, or who are at risk for cancer, and their accompanying family and friends. The Breast Clinic at RPCI actively enrolls patients into the DBBR with accruals of approximately 300 women with breast cancer per year. Tumor tissue is available for the majority of the DBBR participants, and a majority also provides extensive epidemiologic data, including a detailed food frequency questionnaire. Within the framework of this unique and rich resource, we propose to conduct an investigation of dietary lignan intakes with a number of tumor characteristics associated with prognosis in breast cancer. Using tissue blocks from 500 women with incident, primary, histologically-confirmed invasive breast cancer enrolled in the DBBR, and measures of dietary lignan intakes from the DBBR food frequency questionnaire, we will evaluate the following specific aims: 1) examine tumor proliferation (Ki-67), apoptosis (caspase), and tumor growth (Ki- 67:caspase ratio) rates associated with lignan intakes; 2) examine growth factor and signaling pathway protein expression (ERa, ER¿, ERa: ER¿ ratio, PgR, HER2, IGF1, IGFIR) associated with dietary lignan intakes; and 3) examine the association of breast tumor subtype (luminal A, luminal B, HER2, and basal-like) with dietary lignan intakes. We will also investigate the potential modification of the associations between dietary lignan intakes and tumor characteristics by characteristics such as age, body mass index, reproductive history, nutrient intakes, and other related data. Lignans are plant compounds that can act as hormones or restrict cancer growth through other mechanisms. The proposed study will investigate the association of dietary lignan intakes, as amounts commonly consumed in usual diets, with several hormone and growth-related tumor characteristics, many of which are related to breast cancer prognosis. The results of this study may provide us with important information that can be useful in understanding the effect of diet on development of different breast cancer sub-types.