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

  • Ana M. Soto
  • Cathrin Brisken
  • Cheryl Schaeberle
  • Carlos Sonnenschein
Article

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.

Keywords

Xenoestrogen Progesterone receptor Beaded duct Ecological developmental biology Tissue organization field theory Neoplasia 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ana M. Soto
    • 1
    • 2
  • Cathrin Brisken
    • 3
  • Cheryl Schaeberle
    • 1
  • Carlos Sonnenschein
    • 1
    • 2
  1. 1.Tufts University School of MedicineBostonUSA
  2. 2.Sackler School of Graduate Biomedical SciencesTufts University School of MedicineBostonUSA
  3. 3.Ecole polytechnique fédérale de Lausanne, ISREC - Swiss Institute for Experimental Cancer ResearchNCCR Molecular OncologyLausanneSwitzerland

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