title: Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERalpha-positive breast carcinomas.
abstract: BACKGROUND
  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 (ERalpha), 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 beta-hexachlorocyclohexane. When the whole sample was analyzed, no correlation between ERalpha or PR expression and OCC levels were found. In the subgroup of ERalpha-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 ERalpha-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.
  
  
  CONCLUSIONS
  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 ERalpha activation and ERalpha-dependent proliferation. These findings may have therapeutic implications, since interference between organochlorine compounds and hormonal therapy could be expected to occur.
authors.affiliation: Laboratorio de Endocrinología y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Santa Fe, Argentina. monicamt@fbcb.unl.edu.ar
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-de-Toro
authors.forename: Milena
authors.initials: M
authors.lastname: Durando
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Beldoménico
authors.forename: Horacio R
authors.initials: HR
authors.lastname: Beldoménico
authors.forename: Laura
authors.initials: L
authors.lastname: Kass
authors.forename: Silvia R
authors.initials: SR
authors.lastname: García
authors.forename: Enrique H
authors.initials: EH
authors.lastname: Luque
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000368:Aged; D001118:Argentina; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001940:Breast / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D003430:Cross-Sectional Studies; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D008875:Middle Aged; D010573:Pesticide Residues; D017698:Postmenopause; D014505:Urban Population
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D004967:Estrogens; D006843:Hydrocarbons, Chlorinated; D010573:Pesticide Residues