First full-term pregnancies occurring early in life, afford the mother a substantial lifetime protection from breast cancer. The reasons for such protection are unknown, but many experimental observations in rodents suggest that the prolonged elevation in specific circulating hormones in pregnancy play a fundamental role in mammary proliferation and differentiation and reduce the effects of carcinogenic insults. In a case-control study (1890 cases, 3780 controls) nested within two large cohorts in Finland and Sweden totaling over 1.2 million subjects we will explore putative associations between circulating concentrations of a panel of endogenous hormones measured in stored specimens obtained during a primiparous full-term pregnancy and the subsequent occurrence of breast cancer in the mother. Nordic countries provide a unique setting for such a study because of the availability of large, centralized maternity cohorts and the access to a network of high quality nationwide databases, including cancer, population and birth registries, through which most of the information needed to carry out the proposed study will be obtained.
Specific aims are the following: 1) To extend our preliminary observations on the protective role of first-trimester chronic gonadotropin (hCG). We hypothesize that the protection of hCG is maximal when the pregnancy occurs at young age and that the protection decreases with increasing age at pregnancy. Three groups of cases and controls will be studied defined on age at the pregnancy blood donation: <25 years, 25-29 years and 30-39 years 2) To determine whether or not associations similar to those hypothesized for hCG also apply to steroid hormones, as the experimental literature suggests. We will measure estradiol, progesterone, testosterone, and sex-hormone binding globulin (SHBG). With the proposed study we seek to cast light into the biological basis of the lifetime protection from breast cancer of a first full-term pregnancy experienced at young age-one of the best known protective associations in breast cancer epidemiology. A better understanding of such a protection will expand our comprehension of breast cancer and may open up new possibilities to devise and test novel preventive strategies, including chemoprevention, based on the ability to mimic the protective effect of pregnancy.
