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Breast Cancer Research
Published in: Breast Cancer Research 3/2013

Open Access 01-06-2013 | Research article

Circulating serum xenoestrogens and mammographic breast density

Authors: Brian L Sprague, Amy Trentham-Dietz, Curtis J Hedman, Jue Wang, Jocelyn DC Hemming, John M Hampton, Diana SM Buist, Erin J Aiello Bowles, Gale S Sisney, Elizabeth S Burnside

Published in: Breast Cancer Research | Issue 3/2013

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Abstract

Introduction

Humans are widely exposed to estrogenically active phthalates, parabens, and phenols, raising concerns about potential effects on breast tissue and breast cancer risk. We sought to determine the association of circulating serum levels of these chemicals (reflecting recent exposure) with mammographic breast density (a marker of breast cancer risk).

Methods

We recruited postmenopausal women aged 55 to 70 years from mammography clinics in Madison, Wisconsin (N = 264). Subjects completed a questionnaire and provided a blood sample that was analyzed for mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, butyl paraben, propyl paraben, octylphenol, nonylphenol, and bisphenol A (BPA). Percentage breast density was measured from mammograms by using a computer-assisted thresholding method.

Results

Serum BPA was positively associated with mammographic breast density after adjusting for age, body mass index, and other potentially confounding factors. Mean percentage density was 12.6% (95% confidence interval (CI), 11.4 to 14.0) among the 193 women with nondetectable BPA levels, 13.7% (95% CI, 10.7 to 17.1) among the 35 women with detectable levels below the median (<0.55 ng/ml), and 17.6% (95% CI, 14.1 to 21.5) among the 34 women with detectable levels above the median (>0.55 ng/ml; Ptrend = 0.01). Percentage breast density was also elevated (18.2%; 95% CI, 13.4 to 23.7) among the 18 women with serum mono-ethyl phthalate above the median detected level (>3.77 ng/ml) compared with women with nondetectable BPA levels (13.1%; 95% CI, 11.9 to 14.3; Ptrend = 0.07). No other chemicals demonstrated associations with percentage breast density.

Conclusions

Postmenopausal women with high serum levels of BPA and mono-ethyl phthalate had elevated breast density. Further investigation of the impact of BPA and mono-ethyl phthalate on breast cancer risk by using repeated serum measurements or other markers of xenoestrogen exposure are needed.
Appendix
Available only for authorised users
Literature
1.
Committee on the Health Risks of Phthalates: Phthalates and Cumulative Risk Assessment: the Tasks Ahead. 2008, Washington, DC: National Research Council
2.
Soni MG, Carabin IG, Burdock GA: Safety assessment of esters of p-hydroxybenzoic acid (parabens). Food Chem Toxicol. 2005, 43: 985-1015. 10.1016/j.fct.2005.01.020.CrossRefPubMed
3.
Vandenberg LN, Chahoud I, Heindel JJ, Padmanabhan V, Paumgartten FJ, Schoenfelder G: Urinary, circulating, and tissue biomonitoring studies indicate widespread exposure to bisphenol A. Environ Health Perspect. 2010, 118: 1055-1070. 10.1289/ehp.0901716.CrossRefPubMedPubMedCentral
4.
Calafat AM, Ye X, Wong LY, Bishop AM, Needham LL: Urinary concentrations of four parabens in the U.S. population: NHANES 2005-2006. Environ Health Perspect. 2010, 118: 679-685. 10.1289/ehp.0901560.CrossRefPubMedPubMedCentral
5.
Silva MJ, Barr DB, Reidy JA, Malek NA, Hodge CC, Caudill SP, Brock JW, Needham LL, Calafat AM: Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999-2000. Environ Health Perspect. 2004, 112: 331-338.CrossRefPubMedPubMedCentral
6.
Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL: Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Perspect. 2008, 116: 39-44.CrossRefPubMed
7.
Jobling S, Reynolds T, White R, Parker MG, Sumpter JP: A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. Environ Health Perspect. 1995, 103: 582-587. 10.1289/ehp.95103582.CrossRefPubMedPubMedCentral
8.
Harris CA, Henttu P, Parker MG, Sumpter JP: The estrogenic activity of phthalate esters in vitro. Environ Health Perspect. 1997, 105: 802-811. 10.1289/ehp.97105802.CrossRefPubMedPubMedCentral
9.
Laws SC, Carey SA, Ferrell JM, Bodman GJ, Cooper RL: Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats. Toxicol Sci. 2000, 54: 154-167. 10.1093/toxsci/54.1.154.CrossRefPubMed
10.
Borch J, Ladefoged O, Hass U, Vinggaard AM: Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats. Reprod Toxicol. 2004, 18: 53-61. 10.1016/j.reprotox.2003.10.011.CrossRefPubMed
11.
12.
Anderson D, Yu TW, Hincal F: Effect of some phthalate esters in human cells in the comet assay. Teratog Carcinog Mutagen. 1999, 19: 275-280. 10.1002/(SICI)1520-6866(1999)19:4<275::AID-TCM4>3.0.CO;2-1.CrossRefPubMed
13.
Kang SC, Lee BM: DNA methylation of estrogen receptor alpha gene by phthalates. J Toxicol Environ Health A. 2005, 68: 1995-2003. 10.1080/15287390491008913.CrossRefPubMed
14.
Sugiura-Ogasawara M, Ozaki Y, Sonta S, Makino T, Suzumori K: Exposure to bisphenol A is associated with recurrent miscarriage. Hum Reprod. 2005, 20: 2325-2329. 10.1093/humrep/deh888.CrossRefPubMed
15.
Lang IA, Galloway TS, Scarlett A, Henley WE, Depledge M, Wallace RB, Melzer D: Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008, 300: 1303-1310. 10.1001/jama.300.11.1303.CrossRefPubMed
16.
Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM: DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod. 2007, 22: 688-695.CrossRefPubMed
17.
Reddy BS, Rozati R, Reddy S, Kodampur S, Reddy P, Reddy R: High plasma concentrations of polychlorinated biphenyls and phthalate esters in women with endometriosis: a prospective case control study. Fertil Steril. 2006, 85: 775-779. 10.1016/j.fertnstert.2005.08.037.CrossRefPubMed
18.
Wolff MS, Teitelbaum SL, Pinney SM, Windham G, Liao L, Biro F, Kushi LH, Erdmann C, Hiatt RA, Rybak ME, Calafat AM: Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect. 2010, 118: 1039-1046. 10.1289/ehp.0901690.CrossRefPubMedPubMedCentral
19.
Colon I, Caro D, Bourdony CJ, Rosario O: Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ Health Perspect. 2000, 108: 895-900.CrossRefPubMedPubMedCentral
20.
Lopez-Carrillo L, Hernandez-Ramirez RU, Calafat AM, Torres-Sanchez L, Galvan-Portillo M, Needham LL, Ruiz-Ramos R, Cebrian ME: Exposure to phthalates and breast cancer risk in northern Mexico. Environ Health Perspect. 2010, 118: 539-544.CrossRefPubMed
21.
Boyd NF, Martin LJ, Bronskill M, Yaffe MJ, Duric N, Minkin S: Breast tissue composition and susceptibility to breast cancer. J Natl Cancer Inst. 2010, 102: 1224-1237. 10.1093/jnci/djq239.CrossRefPubMedPubMedCentral
22.
Cummings SR, Tice JA, Bauer S, Browner WS, Cuzick J, Ziv E, Vogel V, Shepherd J, Vachon C, Smith-Bindman R, Kerlikowske K: Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst. 2009, 101: 384-398. 10.1093/jnci/djp018.CrossRefPubMedPubMedCentral
23.
Buist DS, Anderson ML, Reed SD, Aiello Bowles EJ, Fitzgibbons ED, Gandara JC, Seger D, Newton KM: Short-term hormone therapy suspension and mammography recall: a randomized trial. Ann Intern Med. 2009, 150: 752-765. 10.7326/0003-4819-150-11-200906020-00003.CrossRefPubMedPubMedCentral
24.
McTiernan A, Martin CF, Peck JD, Aragaki AK, Chlebowski RT, Pisano ED, Wang CY, Brunner RL, Johnson KC, Manson JE, Lewis CE, Hulka BS: Estrogen-plus-progestin use and mammographic density in postmenopausal women: Women's Health Initiative randomized trial. J Natl Cancer Inst. 2005, 97: 1366-1376. 10.1093/jnci/dji279.CrossRefPubMed
25.
Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW: Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004, 96: 621-628. 10.1093/jnci/djh106.CrossRefPubMed
26.
Sprague BL, Trentham-Dietz A, Gangnon RE, Buist DS, Burnside ES, Aiello Bowles EJ, Stanczyk FZ, Sisney GS, Skinner HG: The vitamin D pathway and mammographic breast density among postmenopausal women. Breast Cancer Res Treat. 2012, 131: 255-265. 10.1007/s10549-011-1726-5.CrossRefPubMed
27.
Sprague BL, Trentham-Dietz A, Gangnon RE, Buist DS, Burnside ES, Bowles EJ, Stanczyk FZ, Sisney GS: Circulating sex hormones and mammographic breast density among postmenopausal women. Horm Cancer. 2011, 2: 62-72. 10.1007/s12672-010-0056-0.CrossRefPubMedPubMedCentral
28.
Silva MJ, Malek NA, Hodge CC, Reidy JA, Kato K, Barr DB, Needham LL, Brock JW: Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003, 789: 393-404. 10.1016/S1570-0232(03)00164-8.CrossRefPubMed
29.
Ye X, Tao LJ, Needham LL, Calafat AM: Automated on-line column-switching HPLC-MS/MS method for measuring environmental phenols and parabens in serum. Talanta. 2008, 76: 865-871. 10.1016/j.talanta.2008.04.034.CrossRefPubMed
30.
Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ: The quantitative analysis of mammographic densities. Phys Med Biol. 1994, 39: 1629-1638. 10.1088/0031-9155/39/10/008.CrossRefPubMed
31.
Schafer JL: Analysis of Incomplete Multivariate Data. 1997, London: Chapman and HallCrossRef
32.
Rubin DB: Multiple Imputation for Nonresponse in Surveys. 1987, New York: John Wiley & SonsCrossRef
33.
Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ: Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst. 1995, 87: 670-675. 10.1093/jnci/87.9.670.CrossRefPubMed
34.
Maskarinec G, Meng L: A case-control study of mammographic densities in Hawaii. Breast Cancer Res Treat. 2000, 63: 153-161. 10.1023/A:1006486319848.CrossRefPubMed
35.
Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G: Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst. 2003, 95: 30-37. 10.1093/jnci/95.1.30.CrossRefPubMed
36.
Koch HM, Preuss R, Angerer J: Di(2-ethylhexyl)phthalate (DEHP): human metabolism and internal exposure: an update and latest results. Int J Androl. 2006, 29: 155-165. 10.1111/j.1365-2605.2005.00607.x. discussion 81-85CrossRefPubMed
37.
Stahlhut RW, Welshons WV, Swan SH: Bisphenol A data in NHANES suggest longer than expected half-life, substantial nonfood exposure, or both. Environ Health Perspect. 2009, 117: 784-789.CrossRefPubMedPubMedCentral
38.
Fernandez MF, Arrebola JP, Taoufiki J, Navalon A, Ballesteros O, Pulgar R, Vilchez JL, Olea N: Bisphenol-A and chlorinated derivatives in adipose tissue of women. Reprod Toxicol. 2007, 24: 259-264. 10.1016/j.reprotox.2007.06.007.CrossRefPubMed
39.
Keri RA, Ho SM, Hunt PA, Knudsen KE, Soto AM, Prins GS: An evaluation of evidence for the carcinogenic activity of bisphenol A. Reprod Toxicol. 2007, 24: 240-252. 10.1016/j.reprotox.2007.06.008.CrossRefPubMedPubMedCentral
40.
National Toxicology Program: NTP-CERHR Monograph on the Potential Human Reproductive and Development Effect of Bisphenol A. 2008, Research Triangle Park, NC, NIH Publication No. 08-5994
41.
Durando M, Kass L, Piva J, Sonnenschein C, Soto AM, Luque EH, Munoz-de-Toro M: Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats. Environ Health Perspect. 2007, 115: 80-86. 10.1289/ehp.115-a80.CrossRefPubMed
42.
Munoz-de-Toro M, Markey CM, Wadia PR, Luque EH, Rubin BS, Sonnenschein C, Soto AM: Perinatal exposure to bisphenol-A alters peripubertal mammary gland development in mice. Endocrinology. 2005, 146: 4138-4147. 10.1210/en.2005-0340.CrossRefPubMedPubMedCentral
43.
Melzer D, Harries L, Cipelli R, Henley W, Money C, McCormack P, Young A, Guralnik J, Ferrucci L, Bandinelli S, Corsi AM, Galloway T: Bisphenol A exposure is associated with in vivo estrogenic gene expression in adults. Environ Health Perspect. 2011, 119: 1788-1793. 10.1289/ehp.1103809.CrossRefPubMedPubMedCentral
44.
Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N: Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect. 2008, 116: 1642-1647. 10.1289/ehp.11537.CrossRefPubMedPubMedCentral
45.
46.
Hauser R, Meeker JD, Park S, Silva MJ, Calafat AM: Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect. 2004, 112: 1734-1740. 10.1289/ehp.7212.CrossRefPubMedPubMedCentral
47.
Peck JD, Sweeney AM, Symanski E, Gardiner J, Silva MJ, Calafat AM, Schantz SL: Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age. J Expo Sci Environ Epidemiol. 2010, 20: 90-100. 10.1038/jes.2009.4.CrossRefPubMed
48.
Nepomnaschy PA, Baird DD, Weinberg CR, Hoppin JA, Longnecker MP, Wilcox AJ: Within-person variability in urinary bisphenol A concentrations: measurements from specimens after long-term frozen storage. Environ Res. 2009, 109: 734-737. 10.1016/j.envres.2009.04.004.CrossRefPubMedPubMedCentral
49.
Braun JM, Smith KW, Williams PL, Calafat AM, Berry K, Ehrlich S, Hauser R: Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy. Environ Health Perspect. 2012, 120: 739-745. 10.1289/ehp.1104139.CrossRefPubMedPubMedCentral
50.
Baird DD, Saldana TM, Nepomnaschy PA, Hoppin JA, Longnecker MP, Weinberg CR, Wilcox AJ: Within-person variability in urinary phthalate metabolite concentrations: measurements from specimens after long-term frozen storage. J Exposure Sci Environ Epidemiol. 2010, 20: 169-175. 10.1038/jes.2009.17.CrossRef
Metadata
Title
Circulating serum xenoestrogens and mammographic breast density
Authors
Brian L Sprague
Amy Trentham-Dietz
Curtis J Hedman
Jue Wang
Jocelyn DC Hemming
John M Hampton
Diana SM Buist
Erin J Aiello Bowles
Gale S Sisney
Elizabeth S Burnside
Publication date
01-06-2013
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2013
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr3432

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