© 2000 by Oxford University Press
Journal of the National Cancer Institute, Vol. 92, No. 12, 1001-1005,
June 21, 2000
© 2000 Oxford University Press
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-Fetoprotein Levels in Maternal Serum During Pregnancy and Maternal Breast Cancer Incidence
Affiliations of authors: M. Melbye, J. Wohlfahrt, U. Lei (Department of Epidemiology Research, Danish Epidemiology Science Center), B. Nørgaard-Pedersen (Department of Clinical Biochemistry), Staten Serum Institut, Copenhagen, Denmark; H. T. Mouridsen, Danish Breast Cancer Cooperative Group, Rigshospitalet, Copenhagen; M. Lambe, Department of Medical Epidemiology, Karolinska Institute, Stockholm, Sweden; K. B. Michels, Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health, Boston, MA.
Correspondence to: Mads Melbye, M.D., Department of Epidemiology Research, Statens Serum Institut, 5 Artillerivej, DK-2300 Copenhagen S, Denmark (e-mail: mme{at}ssi.dk).
Background: A full-term pregnancy is associated with a reduced risk of breast cancer, but the underlying biologic mechanism has not been elucidated. During pregnancy, maternal serum levels of 
-fetoprotein, an estradiol-binding protein, rise sharply. In culture, -fetoprotein inhibits the growth of estrogen-sensitive cells, including estrogen-sensitive breast cancer cells. Thus, we investigated whether a high level of -fetoprotein in maternal serum during pregnancy is associated with a reduced risk of breast cancer. Methods: From a population-based cohort of 42057 pregnant women in Denmark, enrolled in an -fetoprotein-screening program from 1978 through 1996, we obtained a complete reproductive history, vital status, and a possible diagnosis of breast cancer (in 117 women) to the end of follow-up on September 1, 1998. Results: During pregnancy, women with an -fetoprotein level greater than or equal to the median value had a 41% lower risk of breast cancer than women with an -fetoprotein level below the median value (relative risk [RR] = 0.59; 95% confidence interval [CI] = 0.41–0.85). RRs for breast cancer by mother's age at childbirth were as follows: 29 years or younger, RR = 0.21 (95% CI = 0.08–0.56); 30–34 years, RR = 0.61 (95% CI = 0.32–1.14); 35–37 years, RR = 0.96 (95% CI = 0.49–1.89); and 38 years or older, RR = 0.71 (95% CI = 0.29–1.75) (P for trend = .02). Further analyses suggested that high levels of -fetoprotein were associated with a reduced incidence of aggressive disease. The most striking finding was that women with high levels of serum -fetoprotein, compared with women with low levels of serum -fetoprotein, showed a particularly reduced incidence of large tumors (>2 cm; RR = 0.24 [95% CI = 0.11–0.50]). Conclusion: A high level of -fetoprotein in maternal serum during any pregnancy is associated with a low overall incidence of breast cancer and, in particular, with a low incidence of advanced breast cancer at diagnosis. This association appears particularly strong for a pregnancy occurring at a young age.
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