Pregnancy Hormonal Profile/Biomarker Breast Cancer Risk

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DESCRIPTION (provided by applicant): A large body of epidemiological evidence indicates that an early first full-term pregnancy (before age 25) confers a lasting protection against breast cancer in the mother. Protection increases with decreasing age at pregnancy and is by and large independent of parity. Long-term protective effect of early full-term pregnancy could arise through pregnancy-related hormonal changes causing proliferation and full differentiation of mammary glandular epithelium in preparation for lactation. Fully differentiated mammary glandular cells are less susceptible to neoplastic transformation, while the vast majority of breast carcinomas arise from undifferentiated glandular cells. Experimental evidence revealed that specific hormones, such as human chorionic gonadotropin (hCG), relaxin (RLX) and alpha-fetoprotein (AFP), may play a role in breast tissue differentiation, and may be responsible for the protective effect of pregnancy on breast cancer risk. Recent data demonstrate that compared to Caucasian women in the US, Asian women had significantly higher second and third trimester levels of hormones affecting breast proliferation, such as estradiol (E2), estriol (E3), prolactin (PRL), and growth hormone (GH). These data support the hypothesis that women at low risk of breast cancer may have a specific hormonal profile during their pregnancies than women at high risk of breast cancer. We propose to expand these observations in a cross-sectional study by comparing pregnancy hormone levels affecting breast differentiation (hCG, RLX, AFP) and proliferation (E2, E3, PRL, GH) in women at high risk (Caucasian and African-American women in New York), intermediate risk (Latina immigrants in New York) and low risk (Asian immigrants in New York) of breast cancer. If the study hypothesis is confirmed, hormonal profile during pregnancy can be used for determination of a woman?s risk of breast cancer later in life. Moreover, specific hormone(s) or its analogues responsible for protective effect of pregnancy against breast cancer could be used for development of novel strategies for primary chemoprevention of breast cancer.