| Lifetime estrogen exposure is considered the main risk factor for the development of breast cancer. Perturbations in the fetal environment predispose individuals to diseases which become apparent in adulthood. For these reasons, scientists have hypothesized that exposure to environmental estrogens during fetal development could increase a woman's propensity to develop breast cancer.; There is widespread human exposure to bisphenol-A (BPA), an estrogenic compound that leaches from dental materials, food and beverage containers and other plastic consumer products. BPA has been detected in human plasma, amniotic fluid, placenta, umbilical cords, and breast milk, making exposure of human neonates and infants a very real concern. Our studies on CD-1 mice revealed that perinatal exposure to environmentally relevant levels of BPA induced alterations in the mammary gland architecture that became apparent at puberty and in adulthood. We have now demonstrated that BPA alters both the epithelial and stromal compartments of the developing mammary gland at embryonic day 18, during the period of exposure, suggesting that the alterations observed later in life have their origins in fetal development.; Perinatal BPA exposure increased the number of terminal end buds at puberty and enhanced sensitivity to estradiol following ovariectomy. By 4 months of age, perinatal BPA exposure increased lateral branching, significantly increased epithelial density at 6 months of age and finally, by 9 months of age, BPA-exposed animals showed intraductal hyperplasias, preneoplastic lesions that manifest as "beaded ducts" in the mammary gland. All of these parameters are associated with an increased risk for developing breast cancer in humans. Additional studies in the rat model suggest that gestational exposure to BPA induces the development of carcinomas in situ in the absence of any additional treatment aimed at increasing tumor development.; Emerging epidemiological data reveal an increased incidence of breast cancer in women exposed to the synthetic estrogen diethylstilbestrol during gestation. These findings, together with evidence collected using experimental models and reported herein, buttress the hypothesis that exposure to environmental estrogens plays a role in the increased incidence of breast cancer observed in European and US populations over the last 50 years. |
