Estrogenic microenvironment generated by organochlorine residues in adipose mammary tissue modulates biomarker expression in ERalpha-positive breast carcinomas.

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 (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. 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 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.

Organochlorine levels in adipose tissue of women from a littoral region of Argentina.

Organochlorine compounds (OCCs), such as pesticides and polychlorinated biphenyls (PCBs), are persistent lipophilic chemicals identified as endocrine disruptors, mainly with estrogen-like effects. Northeastern Argentina, near the Paraná River, is characterized by intensive farming and agricultural activities and industrial development, and is therefore prone to high incidences of environmental and dietary exposure to OCCs. Hence, we conducted a study to (1) estimate the organochlorine residues present in mammary fat tissue in a population of women from this littoral region and (2) identify potential sources of exposure to OCCs. Our subjects were 76 women (residing in and around Santa Fe city and not occupationally exposed to organochlorines) who underwent excision biopsy of a breast lesion or had plastic surgery. Both frequency of occurrence and levels of organochlorine residues were high in breast adipose tissue of all the participants. The organochlorine residues most frequently found were p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in all the subjects analyzed, hexachlorobenzene (HCB) in 86.8%, and beta-hexachlorocyclohexane (beta-HCH) in 75.0%. The incidence of PCB congeners was very low. p,p'-DDE and beta-HCH residues reached the highest levels, 4794 and 1780 ppb, respectively. The diet was a relevant source of exposure, consumption of animal fat and freshwater fish playing a significant role. Bioaccumulation was evidenced by the significant positive association between organochlorine levels and body mass index (p = 0.0003) and the age of the patient (p = 0.0002). The frequency and levels of OCCs found in our study population raise concerns regarding Argentinean exposure to these endocrine disruptors.