Abstract
IntroductionBreast 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.MethodsThe 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 (ERα), progesterone receptor (PR) and proliferative activity (Ki-67) levels were measured in paraffin-embedded biopsies of breast tumors by immunohistochemistry.ResultsAll patients had high levels of organochlorine pesticides in their breast adipose tissue. The most frequently detected compounds were p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene and β-hexachlorocyclohexane. When the whole sample was analyzed, no correlation between ERα or PR expression and OCC levels were found. In the subgroup of ERα-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 ERα-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.ConclusionThe 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 ERα activation and ERα-dependent proliferation. These findings may have therapeutic implications, since interference between organochlorine compounds and hormonal therapy could be expected to occur.
Highlights
Breast cancer is the most frequent malignant disease in women
In the subgroup of ERαpositive breast carcinoma patients, there was a positive correlation between progesterone receptor (PR) expression in the neoplastic cells and Organochlorine compounds (OCCs) levels in adipose tissue surrounding the tumor
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 ERα activation and ERα-dependent proliferation
Summary
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. Exposure to estrogens throughout a woman's life, including the period of intrauterine development, is a risk factor for the development of breast cancer [1,2,3]. DDE = dichlorodiphenyldichloroethylene; DDT = dichlorodiphenyltrichloroethane; ERα = estrogen receptor alpha; GC = gas chromatography; OCC = organochlorine compound; PR = progesterone receptor; T1–T4 = tumor size. Stable and strongly lipophilic, organochlorine compounds (OCCs) have slow degradation rates and tend to bioaccumulate in lipid-rich tissues. Because some OCCs act as estrogen agonists they have been linked to an increased incidence of breast cancer [5,6], not all data have been consistent [7,8,9]
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