Effect of Reproductive History on Mammary Epithelial Biology
Annual rept. 1 May 1999-30 Apr 2000
PENNSYLVANIA UNIV PHILADELPHIA
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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, such as menarche and menopause. This relationship is illustrated by the observation that women who undergo an early first full-tern pregnancy have a significantly reduced lifetime risk of breast cancer. We hypothesize that an early first full-term pregnancy results in a permanent change in the breast that confers a decreased risk for the subsequent development of breast cancer. We further hypothesize that parity-induced changes in the number and distribution of specific epithelial cell subtypes in the breast may contribute to parity-induced changes in breast cancer risk. To address these hypotheses, we are identifying and evaluating molecular biomarkers for parity-induced changes in the breast by isolating genes that are differentially expressed between the parous and nulliparous rodent breast using DNA chip technology. These differentially expressed genes are being used as biomarkers to determine the molecular and cellular changes that occur in the mammary gland as a result of parity. Ultimately, these studies will serve as a step towards determining the mechanisms by which breast cancer susceptibility is modulated by reproductive history.
- Medicine and Medical Research