alpha-fetoprotein levels in maternal serum during pregnancy and maternal breast cancer incidence.
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]).


CONCLUSIONS
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.
Melbye
M
M
Department of Epidemiology Research, Danish Epidemiology Science Center, Staten Serum Institut, Copenhagen, Denmark. mme@ssi.dk
Wohlfahrt
J
J
Lei
U
U
Nørgaard-Pedersen
B
B
Mouridsen
H T
HT
Lambe
M
M
Michels
K B
KB
D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000097:blood* / Q000737:chemistry / Q000453:epidemiology* / Q000473:pathology; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011247:Pregnancy / Q000097:blood*; D011960:Receptors, Estrogen / Q000032:analysis; D012306:Risk; D000509:alpha-Fetoproteins / Q000378:metabolism*
D011960:Receptors, Estrogen; D000509:alpha-Fetoproteins