It is well established that in humans a first full-term pregnancy occurring early in life, afford the mother a substantial lifetime protection from breast cancer. The biological reasons for such protection are unknown, but many experimental observations in rodents suggest that the extended elevation in specific circulating hormones during pregnancy and the resulting prolonged stimulus to mammary cell proliferation and differentiation play a fundamental role in reducing the effect of carcinogenic insults. The overall purpose of this study is to investigate possible protective associations between selected endogenous hormones that have relevant roles in pregnancy and maternal risk of breast cancer. We are addressing this issue in two cohorts, in Finland and Sweden. The Finnish Maternity Cohort (FMC) contains over 1.5 million blood samples obtained during the first trimester of pregnancy from over 850,000 women; the North Sweden Maternity Cohort (NSMC) contains over 110,000 first-trimester blood samples from approximately 83,000 women. Through record linkages with national cancer registries, we estimate that at least 7,000 invasive breast cancers have been diagnosed in the two cohorts. Utilizing these unique resources, we seek to address the hypothesis that a mother?s lifetime risk of breast cancer is markedly reduced after her breasts are exposed for the first time to the full impact of the proliferating and differentiating hormonal stimuli of a pregnancy conducted to term and that such protection is strong when adequate exposure to hormones occurs at a time in life that predates a first carcinogenic hit to the breasts. To test such hypothesis, we are conducting a case-control study (1890 cases, 3780 controls) nested within the two cohorts to explore putative associations between circulating concentrations of a panel of endogenous hormones measured in stored specimens obtained during a primiparous, full-term pregnancy experienced long before cancer diagnosis and the subsequent occurrence of breast cancer in the mother. In preparation for this application, we completed a preliminary case-control study (174 cases, 300 controls) nested in the NSMC, which provided us with information on the feasibility of the research proposed here and valuable preliminary data concerning human chorionic gonadotropin (hCG), one of the primary hormones of interest, suggesting that hCG is protectively associated with breast cancer. These observations, complement a large body of experimental research in rodents indicating that a pregnancy, but also exposure to hCG or estrogens and progesterone in virgin animals, drastically reduce the incidence of carcinogen-induced mammary carcinomas and that this protection is stronger the younger the age at exposure to the hormones.
Research Professor, Department of Obstetrics and Gynecology
MD from Universita degli Studi di Milano
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Pregnancy hormones and maternal risk of hormone receptor-defined breast cancer [Meeting Abstract]
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