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

Abstract

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.

Alpha-foetoprotein in umbilical cord in relation to severe pre-eclampsia, birth weight and future breast cancer risk

“…This finding may reinforce recent experimental evidence that AFP may be a factor with breast cancer inhibiting potential (Bennett et al, 1998, Vakharia andMizejewski, 2000). In adulthood, two studies have recently related maternal blood levels of AFP during the second or third trimester among pregnant women to these women's subsequent risk of breast cancer (Richardson et al, 1998;Melbye et al, 2000). Both studies found that high pregnancy levels of AFP were associated with lower maternal breast cancer risk, and the authors attributed their findings to an anti-oestrogenic effect of AFP.…”

“…Thus, a prospective study in Denmark has shown that high serum concentrations of maternal a-foetoprotein in pregnancy were related to lower risk of maternal breast cancer during follow-up (Melbye et al, 2000). An inverse association between third trimester levels of AFP and subsequent risk of breast cancer has also been reported by an American study (Richardson et al, 1998).…”

Preventing excessive weight gain during pregnancy – a controlled trial in primary health care

“…Several studies have shown that markers of high pregnancy estrogen levels increase mother's breast cancer risk [4][5][6][9][10][11][12]16]. Estrogen levels may correlate with high pregnancy weight gain [19], but two recent studies have not confirmed this observation [20,21].…”

Effects of Parity on Pregnancy Hormonal Profiles Across Ethnic Groups with a Diverse Incidence of Breast Cancer

“…To date, two case-control studies nested within a cohort of predominantly Caucasian pregnant women who were members of the Kaiser Health Plan and enrolled in the Child Health and Development studies (9,44), and one population-based cohort of pregnant women in Denmark (10), investigated the relationships between pregnancy levels of AFP and steroid hormones with subsequent maternal risk of breast cancer.…”