Does Cancer Start in the Womb? Altered Mammary Gland Development and Predisposition to Breast Cancer due to in Utero Exposure to Endocrine Disruptors

Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, USA.
Journal of Mammary Gland Biology and Neoplasia (Impact Factor: 4.53). 05/2013; 18(2). DOI: 10.1007/s10911-013-9293-5
Source: PubMed


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 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.

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Available from: Cathrin Brisken, Sep 14, 2014
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    • "Thus, the impact of BPA must extend beyond immediate transcriptional regulation in both stromal and epithelial cells. Indeed, alterations of the transcriptomes of both tissue compartments observed during the period of exposure may explain the morphological and functional effects observed later in life ([61] and reviewed in [65]). Microarray analyses of rat mammary glands exposed to BPA in utero revealed a host of changes in gene expression in low (25µg/kg/day) and high (250µg/kg/day, oral gavage) dose cohorts [48]. "
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    • "Extensive use of bisphenols caused increasing concern over the potential adverse effects provoked by these substances on human health (Song et al., 2014). The results of in vitro and in vivo studies as well as epidemiological surveys have demonstrated that BPA exhibits endocrine, hepatotoxic and neurotoxic potential and may increase risk of cancer development (Cabaton et al., 2006; Soto et al., 2013). Significantly less attention has been devoted BPA analogues including the effect of these substances on blood cells. "
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    • "One study concluded that somatic sequence variants in normal cell populations could be the earliest stage of oncogenesis [12]. Evidence that altered mammary gland development and predisposition to breast cancer is due to in utero exposure to endocrine disruptors has suggested that selection of cells with different phenotypic properties, presumably as a result of very early somatic mutations, may take place at the very earliest stages of breast tissue development [13]. Thus, we may need to reconsider whether accumulation of a critical number of oncogenic mutations, e.g., the buildup of driver somatic mutations, is the reason that many cancers occur later in life. "
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