) Epidemiologic studies have highlighted the relationship between hormones and carcinogenesis in the breast by identifying endocrine risk factors for breast cancer that are related to the timing of reproductive endocrine events. This relationship is illustrate by the observation that women who undergo an early first full-term pregnancy have a significantly reduced lifetime risk of breast cancer. The recognition that specific reproductive endocrine events alter breast cancer risk in a predictable fashion raises the possibility that events associated with a decrease in breast cancer risk, such as early first full-term pregnancy, might be mimicked pharmacologically. As such, understanding the mechanisms by which these events influence breast cancer risk would facilitate the design of safe and effective hormonal chemoprevention regimens. In addition, the testing of such regimens would be facilitated by the identification of biomarkers that accurately reflect early biological changes in the breast associated with reproductive endocrine events that alter breast cancer susceptibility. We hypothesize that understanding the biological mechanisms by which endogenous hormones exposures influence breast cancer susceptibility will require a thorough understanding of the cell types present in the breast and the manner in which hormones affect their normal programs of differentiation and development.
The specific aims of this proposal are designed to develop molecular biomarkers for parity-induced changes in the breast using an established rodent model for parity-induced protection against breast cancer, to evaluate the utility of these biomarkers in human breast tissue, and to use these biomarkers to explore the molecular and cellular changes that occur in the breast a result of parity. Ultimately, these studies are intended as a step towards determining the mechanisms by which breast cancer susceptibility is modulated by reproductive history.
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