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

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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 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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Notes

  1. Laplacian determination is the one operating in computers where complete knowledge of the state at one moment completely determines its state at all future moments.

  2. A dose of 250 μg/kg/day resulted in unconjugated BPA serum levels in the range of those found in humans (unpublished data, AMS and CS)

Abbreviations

EDC:

Endocrine disrupting chemical

BPA:

Bisphenol-A

DES:

diethylstilbestrol

FDA:

United States Food and Drug Administration

DMBA:

dimethylbenzanthracene

DDT:

dichlorodiphenyltrichloroethane

PCB:

polychlorinated biphenyl

SMT:

somatic mutation theory

TOFT:

tissue organization field theory

bw:

bodyweight

CDC:

United States Centers for Disease Control and Prevention

GD:

Gestational day

E:

embryonic day

ERs:

Estrogen receptors

PR:

progesterone receptor

PND:

postnatal day

ECM:

extracellular matrix

TEB:

terminal end bud

SPARC:

secreted protein acidic and rich in cysteine

EPA:

United States Environmental Protection Agency

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Acknowledgments

We thank Tessie Paulose and Nicole Acevedo for their editorial assistance. This research was supported by The Avon Foundation grant #02-2009-093, and 02-2011-095 as well as by the National Institute of Environmental Health Sciences, Award Numbers R01ES08314, RC2ES018822 and U01ES020888. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Environmental Health Sciences or the National Institutes of Health.

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Correspondence to Carlos Sonnenschein.

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Soto, A.M., Brisken, C., Schaeberle, C. et al. 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 18, 199–208 (2013). https://doi.org/10.1007/s10911-013-9293-5

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