Research article
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Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ER?-positive breast carcinomas
Mónica Muñoz-de-Toro1 , Milena Durando1 , Pablo M Beldoménico1 ,2 , Horacio R Beldoménico3 , Laura Kass1 , Silvia R GarcÃ*a3 and Enrique H Luque1
1Laboratorio de EndocrinologÃ*a y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Santa Fe, Argentina
2Faculty of Sciences, University of Liverpool, UK
3Central Laboratory, Pesticide Division, School of Chemical Engineering, Universidad Nacional del Litoral, Santa Fe, Argentina
Breast Cancer Research 2006, 8:R47 doi:10.1186/bcr1534
The electronic version of this article is the complete one and can be found online at:
http://breast-cancer-research.com/content/8/4/R47
Received 13 March 2006
Revisions requested 1 June 2006
Revisions received 8 June 2006
Accepted 13 July 2006
Published 19 July 2006
© 2006 Muñoz-de-Toro et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (
http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Outline Abstract
Abstract
Introduction
Materials and methods
Results
Discussion
Conclusion
Abbreviations
Competing interests
Authors' contributions
Acknowledgements
References
Introduction
Breast cancer is the most frequent malignant disease in women. Exposure to estrogens throughout a woman's life is a risk factor for the development of breast cancer. Organochlorine compounds (OCCs), such as pesticides and polychlorinated biphenyls, are persistent lipophilic chemicals identified as endocrine disruptors, mainly with estrogenic effects. To test the hypothesis that the amount and quality of organochlorine residues in adipose tissue adjacent to breast carcinoma affect the biological behavior of the tumor, we studied biomarker expression in breast carcinoma and the OCC body burden in patients from an urban area adjacent to Paraná fluvial system, Argentina.
Methods
The studied patients were 55 women who had undergone excision biopsies of a breast lesion diagnosed as invasive breast carcinoma. Analysis of OCC residues in breast adipose tissue was conducted by electron-capture gas–liquid chromatography. Estrogen receptor alpha (ER?), progesterone receptor (PR) and proliferative activity (Ki-67) levels were measured in paraffin-embedded biopsies of breast tumors by immunohistochemistry.
Results
All patients had high levels of organochlorine pesticides in their breast adipose tissue. The most frequently detected compounds were p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene and ?-hexachlorocyclohexane. When the whole sample was analyzed, no correlation between ER? or PR expression and OCC levels were found. In the subgroup of ER?-positive breast carcinoma patients, however, there was a positive correlation between PR expression (an estrogen-induced protein) in the neoplastic cells and OCC levels in adipose tissue surrounding the tumor. More significantly, all the ER?-positive breast carcinomas from postmenopausal women exhibited high proliferation when organochlorine levels in the surrounding adipose tissue reached levels higher than 2600 ppb. No associations were found between the organochlorine body burden and any other marker of tumor aggressiveness, such as node involvement or tumor size.
Conclusion
The present results support the hypothesis that organochlorine residues in adipose tissue adjacent to breast carcinoma generate an estrogenic microenvironment that may influence the biological behavior of the tumor through ER? activation and ER?-dependent proliferation. These findings may have therapeutic implications, since interference between organochlorine compounds and hormonal therapy could be expected to occur.
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