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Early Life Exposure to Bisphenol A and Breast Neoplasia

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Environment and Breast Cancer

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Abstract

Excess estrogen exposure in developing individuals increases the risk of developing breast cancer later in life. This excess estrogen can originate from high levels of maternal endogenous estrogens or from exposure to exogenous endocrine disrupting compounds that mimic estrogen actions. One of those ­compounds is the ubiquitous bisphenol A or BPA, a chemical that has been found in over 90% of the American population tested and that mimics the actions of estradiol both in vitro and in vivo. The breast is a target organ for both estradiol and BPA. In this chapter we will discuss the effects of BPA on the developing mammary gland and its long-lasting consequences on the organ’s health, and we will argue that prenatal and early life exposure to endocrine disrupting chemicals contributes to the increased incidence of breast cancer observed during the last decades.

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References

  • Anbazhagan R, Bartek J, Monaghan P, Gusterson BA (1991) Growth and development of the human infant breast. Am J Anat 192:407–417

    Article  PubMed  CAS  Google Scholar 

  • Andersen M, Kiel P, Larsen H, Maxild U (1975) Mutagenic action of arobatic epoxy resins. Nature 276:391–392

    Article  Google Scholar 

  • Ashby J, Tennant RW (1988) Chemical structure, Salmonella mutagenicity, and extent of carcinogenicity as indicators of genotoxic carcinogenesis among 222 chemicals tested in rodents by the US NCI/NTP. Mutat Res 204:17–115

    Article  PubMed  CAS  Google Scholar 

  • Bartow SA (1998) Use of the autopsy to study ontogeny and expression of the estrogen receptor gene in human breast. J Mammary Gland Biol Neoplasia 3:37–48

    Article  PubMed  CAS  Google Scholar 

  • Betancourt AM, Mobley JA, Russo J, Lamartiniere CA (2010) Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A. J Proteomics 73:1241–1253

    Article  PubMed  CAS  Google Scholar 

  • Biles JE, McNeal TP, Begley TH, Hollifield HC (1997) Determination of bisphenol-A in reusable polycarbonate food-contact plastics and migration to food simulating liquids. J Agric Food Chem 45:3541–3544

    Article  CAS  Google Scholar 

  • Boylan ES, Calhoon RE (1983) Transplacental action of diethylstilbestrol on mammary carcinogenesis in female rats given one or two doses of 7,12-dimethylbenz(a)anthracene. Cancer Res 43:4879–4884

    PubMed  CAS  Google Scholar 

  • Bromer JG, Zhou Y, Taylor MB, Doherty L, Taylor HS (2010) Bisphenol-A exposure in utero leads to epigenetic alterations in the developmental programming of uterine estrogen response. FASEB J 24:2273–2280

    Article  PubMed  CAS  Google Scholar 

  • Brotons JA, Olea-Serrano MF, Villalobos M, Olea N (1994) Xenoestrogens released from lacquer coating in food cans. Environ Health Perspect 103:608–612

    Article  Google Scholar 

  • Calafat AM, Kuklenyik Z, Reidy JA, Caudill SP, Ekong J, Needham JL (2005) Urinary concentrations of bisphenol A and 4-nonylphenol in a human reference population. Environ Health Perspect 113:391–395

    Article  PubMed  CAS  Google Scholar 

  • Cohn BA, Wolff MS, Cirillo PM, Sholtz RI (2007) DDT and breast cancer in young women: new data on the significance of age at exposure. Environ Health Perspect 115:1406–1414

    PubMed  CAS  Google Scholar 

  • Cunha GR, Bigsby RM, Cooke PS, Sugimura Y (1985) Stromal-epithelial interactions in adult organs. Cell Differ 17:137–148

    Article  PubMed  CAS  Google Scholar 

  • Durando M, Kass L, Piva J, Sonnenschein C, Soto AM, Luque EH, Munoz de Toro MM (2007) Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect 115:80–86

    Article  PubMed  CAS  Google Scholar 

  • Fenton SE, Hamm JT, Birnbaum L, Youngblood GL (2002) Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol Sci 67:63–74

    Article  PubMed  CAS  Google Scholar 

  • Fenton SE, Rudel RA (2010) A multi-laboratory round robin comparison of mammary gland whole mounts contributes to protocol standardization. Society of Toxicology Annual Meeting Abstract #2372

    Google Scholar 

  • Ho S-M, Tang WY, Belmonte de Frausto J, Prins GS (2006) Developmental exposure to estradiol and bisphenol a increases susceptibility to prostate carcinogenesis and epigenetically regulates phosphodiesterase type 4 variant 4. Cancer Res 66:5624–5632

    Article  PubMed  CAS  Google Scholar 

  • Humphreys RC, Krajewska M, Krnacik S, Jæger R, Weiher H, Krajewski S, Reed JC, Rosen JM (1996) Apoptosis in the terminal end bud of the murine mammary gland: a mechanism of ductal morphogenesis. Development 122:4013–4022

    PubMed  CAS  Google Scholar 

  • Izzotti A, Kanitz S, D’Agostini F, Camoirano A, De Flora S (2009) Formation of adducts by bisphenol A, an endocrine disruptor, in DNA in vitro and in liver and mammary tissue of mice. Mutat Res 679:28–32

    PubMed  CAS  Google Scholar 

  • Keeling JW, Özer E, King G, Walker F (2000) Oestrogen receptor alpha in female fetal, infant, and child mammary tissue. J Pathol 191:449–451

    Article  PubMed  CAS  Google Scholar 

  • Lemmen JG, Broekhof JLM, Kuiper GGJM, Gustafsson JA, Van Der Saag PT, van der Burg B (1999) Expression of estrogen receptor alpha and beta during mouse embryogenesis. Mech Dev 81:163–167

    Article  PubMed  CAS  Google Scholar 

  • Ma L, Benson GV, Lim H, Dey SK, Maas RL (1998) Abdominal B (AbdB) Hoxa genes: regulation in adult uterus by estrogen and progesterone and repression in mullerian duct by the synthetic estrogen diethylstilbestrol (DES). Dev Biol 197:141–154

    Article  PubMed  CAS  Google Scholar 

  • Ma R, Sassoon DA (2006) PCBs exert an estrogenic effect through repression of the Wnt7a signaling pathway in the female reproductive tract. Environ Health Perspect 114:898–904

    Article  PubMed  CAS  Google Scholar 

  • Maffini MV, Sonnenschein C, Soto AM (2010) Breast. In: Woodruff TJ, Janssen SJ, Guillette LJ Jr, Giudice LC (eds) Environmental impacts on reproductive health and fertility. Cambridge University Press, Cambridge

    Google Scholar 

  • Markey CM, Luque EH, Munoz de Toro MM, Sonnenschein C, Soto AM (2001a) In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland. Biol Reprod 65:1215–1223

    PubMed  CAS  Google Scholar 

  • Markey CM, Michaelson CL, Sonnenschein C, Soto AM (2001b) Alkylphenols and bisphenol A as environmental estrogens. In: Metzler M (ed) The handbook of environmental chemistry, vol 3, part L, Endocrine disruptors – part I. Springer, Berlin

    Google Scholar 

  • Markey CM, Rubin BS, Soto AM, Sonnenschein C (2003) Endocrine disruptors from Wingspread to environmental developmental biology. J Steroid Biochem Mol Biol 83:235–244

    Article  Google Scholar 

  • Masuda S, Terashima Y, Sano A, Kuruto R, Sugiyama Y, Shimoi K, Tanji K, Yoshioka H, Terao Y, Kinae N (2005) Changes in the mutagenic and estrogenic activities of bisphenol A upon treatment with nitrite. Mutat Res 585:137–146

    PubMed  CAS  Google Scholar 

  • Medina D (2000) The preneoplastic phenotype in murine mammary tumorigenesis. J Mammary Gland Biol Neoplasia 5:393–407

    Article  PubMed  CAS  Google Scholar 

  • Moral R, Wang R, Russo IH, Lamartiniere CA, Pereira J, Russo J (2008) Effect of prenatal ­exposure to the endocrine disruptor bisphenol A on mammary gland morphology and gene expression signature. J Endocrinol 196:101–112

    Article  PubMed  CAS  Google Scholar 

  • Munoz de Toro MM, Markey CM, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM (2005) Perinatal exposure to bisphenol A alters peripubertal mammary gland development in mice. Endocrinology 146:4138–4147

    Article  PubMed  CAS  Google Scholar 

  • Murray TJ, Maffini MV, Ucci AA, Sonnenschein C, Soto AM (2007) Induction of mammary gland ductal hyperplasias and carcinoma in situ following fetal bisphenol A exposure. Reprod Toxicol 23:383–390

    Article  PubMed  CAS  Google Scholar 

  • Myers JP, vom Saal FS, Akingbemi BT et al (2009) Why public health agencies cannot depend on good laboratory practices as a criterion for selecting data: the case of bisphenol A. Environ Health Perspect 117:309–315

    PubMed  CAS  Google Scholar 

  • Nandi S, Guzman R, Yang J (1995) Hormones and mammary carcinogenesis in mice, rats, and humans: a unifying hypothesis. Proc Natl Acad Sci U S A 92:3650–3657

    Article  PubMed  CAS  Google Scholar 

  • Narbaitz R, Stumpf WE, Sar M (1980) Estrogen receptors in the mammary gland primordia of fetal mouse. Anat Embryol 158:161–166

    Article  PubMed  CAS  Google Scholar 

  • Nikaido Y, Yoshizawa K, Danbara N, Tsujita-Kyutoku M, Yuri T, Uehara N, Tsubura A (2004) Effects of maternal xenoestrogen exposure on development of the reproductive tract and ­mammary gland in female CD-1 mouse offspring. Reprod Toxicol 18:803–811

    Article  PubMed  CAS  Google Scholar 

  • National Toxicology Program (2008) NTP-CERHR monograph on the potential human reproductive and developmental effects of Bisphenol A. http://cerhr.niehs.nih.gov/evals/bisphenol/bisphenol.pdf

  • Olea N, Pulgar R, Perez P, Olea-Serrano F, Rivas A, Novillo-Fertrell A, Pedraza V, Soto AM, Sonnenschein C (1996) Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Perspect 104:298–305

    Article  PubMed  CAS  Google Scholar 

  • Palmer JR, Wise LA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter W, Kaufman R, Herbst AL, Noller KL, Hyer M, Hoover RN (2006) Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15:1509–1514

    Article  PubMed  CAS  Google Scholar 

  • Potischman N, Troisi R (1999) In-utero and early life exposures in relation to risk of breast cancer. Cancer Causes Control 10:561–573

    Article  PubMed  CAS  Google Scholar 

  • Rayner JL, Enoch RR, Fenton SE (2005) Adverse effects of prenatal exposure to atrazine during a critical period of mammary gland growth. Toxicol Sci 87:255–266

    Article  PubMed  CAS  Google Scholar 

  • Robinson GW, Karpf ABC, Kratochwil K (1999) Regulation of mammary gland development by tissue interaction. J Mammary Gland Biol Neoplasia 4:9–19

    Article  PubMed  CAS  Google Scholar 

  • Rosen PP (2008) Anatomy and physiologic morphology. In: Rosen’s breast pathology. Lippincott, Williams, and Wilkins, New York

    Google Scholar 

  • Rudel RA, Euling SY, Makris SL, Fenton SE (2010) Mammary gland development as a sensitive indicator of early life exposures: recommendations from an interdisciplinary workshop. Society of Toxicology Annual Meeting Abstract #2404

    Google Scholar 

  • Russo IH, Russo J (1996) Mammary gland neoplasia in long-term rodent studies. Environ Health Perspect 104:938–967

    Article  PubMed  CAS  Google Scholar 

  • Saji S, Jensen EV, Nilsson S, Rylander T, Warner M, Gustafsson J-A (2000) Estrogen receptors a and b in the rodent mammary gland. Proc Natl Acad Sci U S A 97:337–342

    Article  PubMed  CAS  Google Scholar 

  • Schweikl H, Schmalz G, Rackebrandt K (1998) The mutagenic activity of unpolymerized resin monomers in Salmonella typhimurium and V79 cells. Mutat Res 415:119–130

    PubMed  CAS  Google Scholar 

  • Shyamala G, Chou Y-C, Louie SG, Guzman RC, Smith GH, Nandi S (2002) Cellular expression of estrogen and progesterone receptors in mammary glands: regulation by hormones, development and aging. J Steroid Biochem Mol Biol 80:137–148

    Article  PubMed  CAS  Google Scholar 

  • Singh M, McGinley JN, Thompson HJ (2000) A comparison of the histopathology of premalignant and malignant mammary gland lesions induced in sexually immature rats with those occurring in the human. Lab Invest 80:221–231

    Article  PubMed  CAS  Google Scholar 

  • Sonnenschein C, Soto AM (1999) The enormous complexity of cancer. In: The society of cells: cancer and control of cell proliferation. Springer, New York

    Google Scholar 

  • Soto AM, Sonnenschein C (2010) Environmental causes of cancer: endocrine disruptors as carcinogens. Nat Rev Endocrinol 6:363–370

    Article  PubMed  CAS  Google Scholar 

  • Tomooka Y, Bern HA (1982) Growth of mouse mammary glands after neonatal sex hormone treatment. J Natl Cancer Inst 69:1347–1352

    PubMed  CAS  Google Scholar 

  • Trichopoulos D (1990) Is breast cancer initiated in utero? Epidemiology 1:95–96

    PubMed  CAS  Google Scholar 

  • Tsutsui T, Tamura Y, Yagi E, Hasegawa K, Takahashi M, Maizumi N, Yamaguchi F, Barrett JC (1998) Bisphenol-A induces cellular transformation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells. Int J Cancer 75:290–294

    Article  PubMed  CAS  Google Scholar 

  • Tyl RW, Myers CB, Marr MC, Sloan CS, Castillo NP, Veselica MM, Seely JC, Dimond SS, Van Miller JP, Shiotsuka RN, Beyer D, Hentges SG, Waechter JM Jr (2008) Two-generation reproductive toxicity study of dietary bisphenol A in CD-1 (Swiss) mice. Toxicol Sci 104:362–384

    Article  PubMed  CAS  Google Scholar 

  • Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJ, Schoenfelder G (2010) Urinary, circulating and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect 118:1055–1070

    Article  PubMed  CAS  Google Scholar 

  • Vandenberg LN, Maffini MV, Schaeberle CM, Ucci AA, Sonnenschein C, Rubin BS, Soto AM (2008) Perinatal exposure to the xenoestrogen bisphenol-A induces mammary intraductal hyperplasias in adult CD-1 mice. Reprod Toxicol 3–4:210–219

    Article  Google Scholar 

  • Vandenberg LN, Maffini MV, Sonnenschein C, Rubin BS, Soto AM (2009) Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr Rev 30:75–95

    Article  PubMed  CAS  Google Scholar 

  • Vandenberg LN, Maffini MV, Wadia PR, Sonnenschein C, Rubin BS, Soto AM (2007) Exposure to the xenoestrogen bisphenol-A alters development of the fetal mammary gland. Endocrinology 148:116–127

    Article  PubMed  CAS  Google Scholar 

  • Vandenberg LN, Wadia PR, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM (2006) The mammary gland response to estradiol: monotonic at the cellular level, non-monotonic at the tissue-level of organization? J Steroid Biochem Mol Biol 101:263–274

    Article  PubMed  CAS  Google Scholar 

  • Veltmaat JM, Mailleux AA, Thiery JP, Bellusci S (2003) Mouse embryonic mammogenesis as a model for the molecular regulation of pattern formation. Differentiation 71:1–17

    Article  PubMed  CAS  Google Scholar 

  • Wadia PR, Vandenberg LN, Schaeberle CM, Rubin BS, Sonnenschein C, Soto AM (2007) Perinatal bisphenol-A exposure increases estrogen sensitivity of the mammary gland in diverse mouse strains. Environ Health Perspect 115:592–598

    Article  PubMed  CAS  Google Scholar 

  • Warner M, Eskenazi B, Mocarelli P, Gerthoux PM, Samuels S, Needham L, Patterson D, Brambilla P (2002) Serum dioxin concentrations and breast cancer risk in the Seveso Women’s Health Study. Environ Health Perspect 110:625–628

    Article  PubMed  CAS  Google Scholar 

  • Weihua Z, Saji S, Makinen S, Cheng G, Jensen EV, Warner M, Gustafsson J-A (2000) Estrogen receptor (ER) beta, a modulator of ER alpha in the uterus. Proc Natl Acad Sci U S A 97:5936–5941

    Article  PubMed  CAS  Google Scholar 

  • White SS, Calafat AM, Kuklenyik Z, Villanueva L, Zehr RD, Helfant L, Strynar MJ, Lindstrom AB, Thibodeaux JR, Wood C, Fenton SE (2007) Gestational PFOA exposure of mice is associated with altered mammary gland development in dams and female offspring. Toxicol Sci 96:133–144

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA

    Maricel V. Maffini

  2. Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA

    Carlos Sonnenschein & Ana M. Soto

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  1. Maricel V. Maffini
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  2. Carlos Sonnenschein
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  3. Ana M. Soto
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Correspondence to Maricel V. Maffini .

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  1. Lab. Breast Cancer Research, Fox Chase Cancer Center, Burholme Avenue 7701, Philadelphia, 19111, Pennsylvania, USA

    Jose Russo

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Maffini, M.V., Sonnenschein, C., Soto, A.M. (2011). Early Life Exposure to Bisphenol A and Breast Neoplasia. In: Russo, J. (eds) Environment and Breast Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9896-5_4

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