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High maternal serum alpha-fetoprotein (AFP) levels during pregnancy may be instrumental in reducing the subsequent risk of breast cancer. This hypothesis was tested in a nested case-control study using stored frozen sera accrued between 1959 and 1966 by the University of California at Berkeley Child Health and Development Studies (CHDS) group from a cohort of pregnant women. Cases with histologically confirmed breast cancer were identified from California Cancer Registry files covering their date of enrollment in the CHDS until 1994. Controls were selected from the CHDS cohort by using randomized recruitment. Third-trimester maternal serum AFP levels were analyzed by using both a radioimmunoassay and an immunoenzymatic method. After controlling for multiple confounders in logistic regression models, the authors found an inverse association between high levels of maternal serum AFP (top quartile) during the index pregnancy and the risk of breast cancer. The protective effect of high levels of maternal serum AFP varied by age at first full-term pregnancy (age 20 years or less: odds ratio (OR) = 0.43, 95% confidence interval (CI) 0.28-0.65; age 21-23 years: OR = 0.62, 95% CI 0.41-0.92). After age 27 years, the estimated risk exceeded unity (OR = 1.67, 95% CI 1.14-2.45). These study findings suggest that some of the protection against breast cancer conferred by early first full-term pregnancy may result from high levels of maternal serum AFP. After age 27 years, a high maternal serum AFP level is not protective and may increase risk.

Levels of Maternal Serum Alpha-fetoprotein (AFP) in Pregnant Women and Subsequent Breast Cancer Risk