Research article
Estrogenic microenvironment generated by organochlorine
residues in adipose mammary tissue modulates biomarkers
expression in ER????-positive breast carcinomas
Mónica Muñoz-de-Toro1, Milena Durando1, Pablo M. Beldoménico1, *, Horacio
R. Beldoménico2, Laura Kass1, Silvia R. GarcÃ*a2, Enrique H. Luque1
1
Laboratorio de EndocrinologÃ*a y Tumores Hormonodependientes, School of
Biochemistry and Biological Sciences and 2Central Laboratory, Pesticide Division, School
of Chemical Engineering, Universidad Nacional del Litoral, Santa Fe, Argentina
Running title: Estrogenic effect of organochlorine on breast carcinoma.
Keywords: Endocrine disruptors, Organochlorine pesticides, Breast Cancer, Estrogen
Receptor-?, Progesterone Receptor.
Correspondence: Enrique H. Luque, Laboratorio de EndocrinologÃ*a y Tumores
Hormonodependientes, School of Biochemistry and Biological Sciences, Casilla de
Correo 242, (3000) Santa Fe, Argentina. Phone/Fax: 54 342 4575207; E-mail:
eluque@fbcb.unl.edu.ar
*
Present address: Faculty of Sciences, University of Liverpool, U.K.
Abstract
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 (PCBs), 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 OCCs body burden in patients from an urban area adjacent to Paraná fluvial system,
Argentina.
Methods The studied patients were 55 women that had undergone excision biopsies of a
breast lesion diagnosed as invasive breast carcinoma. Analysis of OCCs residues in
breast adipose tissue was conducted by electron-capture gas liquid chromatography.
Estrogen receptor (ER)-?, progesterone receptor (PR) and proliferative activity (Ki-67)
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 (DDE), hexachlorobenzene (HCB) and ?-
hexachlorocyclohexane (?-HCH). When the whole sample was analyzed, no correlation
between ER? or PR expression and OCCs levels were found. However, in the subgroup
of ER?-positive breast carcinoma patients, there was a positive correlation between PR
expression (an estrogen induced protein) in the neoplastic cells and OCCs levels in
adipose tissue surrounding the tumor. More significant, 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 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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