α-fetoprotein levels in maternal serum during pregnancy and maternal breast cancer incidence

Abstract

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 α-fetoprotein, an estradiol- binding protein, rise sharply. In culture, α-fetoprotein inhibits the growth of estrogen-sensitive cells, including estrogen-sensitive breast cancer cells. Thus, we investigated whether a high level of α-fetoprotein in maternal serum during pregnancy is associated with a reduced risk of breast cancer. Methods: From a population-based cohort of 42 057 pregnant women in Denmark, enrolled in an α-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 α-fetoprotein level greater than or equal to the median value had a 41% lower risk of breast cancer than women with an α-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 α-fetoprotein were associated with a reduced incidence of aggressive disease. The most striking finding was that women with high levels of serum α-fetoprotein, compared with women with low levels of serum α-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 α-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.