Does Cancer start in the Womb? Predisposition to Breast Cancer due to in utero Exposure to DES, EDCs

Abstract

We are now witnessing a resurgence of theories of development and carcinogenesis in which the environment is again being accepted as a major player in phenotype determination. Perturbations in the fetal environment predispose an individual to disease that only becomes apparent in adulthood. For example, gestational exposure to Diethylstilbestrol (DES)  resulted in clear cell carcinoma of the vagina and breast cancer.

In this review the effects of the endocrine disruptor bisphenol A (BPA) on mammary development and tumorigenesis in rodents is used as a paradigmatic example of how altered prenatal mammary development may lead to breast cancer in humans who are also widely exposed to it through plastic goods, food and drink packaging, and thermal paper receipts. Changes in the stroma and its extracellular matrix led to altered ductal morphogenesis. Additionally, gestational and lactational exposure to BPA increased the sensitivity of rats and mice to mammotropic hormones during puberty and beyond, thus suggesting a plausible explanation for the increased incidence of breast cancer..

Excerpts

“… Breast cancer risk at 40 years of age and older is 2.5 fold higher in DES-exposed women than in unexposed women of the same age. In rats, prenatal exposure to DES also resulted in increased mammary cancer incidence during adulthood when these animals were challenged with the chemical carcinogen dimethylbenzanthracene (DMBA) at puberty. DES was administered to rats at pharmacological doses to mimic its medical use… ”

“… The causal link between fetal exposure to estrogens and the development of breast cancer that was first suggested by epidemiologists has now been confirmed by the increased risk to develop breast cancer during adulthood of women exposed to DES during their fetal life. Fetal and neonatal exposures to EDCs cause persistent alterations in the mammary glands of rodents, including pre- and neoplastic lesions, long after the exposure ended. In the case of BPA, mammary neoplasias may have their origin in the altered mammary morphogenesis that occurs during fetal and neonatal exposure. The data obtained from laboratory animals support the extrapolation that exposure to BPA and other xenoestrogens during organogenesis in humans contributes to the increase in the incidence of breast cancer observed over recent decades….”

Sources and full study

• Does cancer start in the womb? altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors, J Mammary Gland Biol Neoplasia. PMID: 23702822, 2013 Jun;18(2):199-208. doi: 10.1007/s10911-013-9293-5. Epub 2013 May 24.
• Full study 18(2), 199–208. doi:10.1007/s10911-013-9293-5 PMC3933259, 2013 Jun.

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