alpha-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 alpha-fetoprotein, an estradiol-binding protein, rise sharply. In culture, alpha-fetoprotein inhibits the growth of estrogen-sensitive cells, including estrogen-sensitive breast cancer cells. Thus, we investigated whether a high level of alpha-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 alpha-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 alpha-fetoprotein level greater than or equal to the median value had a 41% lower risk of breast cancer than women with an alpha-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 alpha-fetoprotein were associated with a reduced incidence of aggressive disease. The most striking finding was that women with high levels of serum alpha-fetoprotein, compared with women with low levels of serum alpha-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 alpha-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.

• Authors: M Melbye, J Wohlfahrt, U Lei, B Nørgaard-Pedersen, H T Mouridsen, M Lambe, K B Michels
• Journal: Journal of the National Cancer Institute (J Natl Cancer Inst) Vol. 92 Issue 12 Pg. 1001-5 (Jun 21 2000) ISSN: 0027-8874 [Print] United States
• PMID: 10861312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Receptors, Estrogen
• alpha-Fetoproteins

Topics

• Adult
• Age Factors
• Breast Neoplasms (blood, chemistry, epidemiology, pathology)
• Denmark (epidemiology)
• Female
• Humans
• Incidence
• Lymphatic Metastasis
• Middle Aged
• Pregnancy (blood)
• Receptors, Estrogen (analysis)
• Risk
• alpha-Fetoproteins (metabolism)