Is there an association between exposure to environmental estrogens and breast cancer?

It was initially reported that levels of polychlorinated biphenyls (PCBs) or p,p'-DDE were elevated in breast cancer patients (serum or tissue) versus controls. These results, coupled with reports that selected environmental estrogens decreased 17β-estradiol (E₂) 2-hydroxylase activity and increased the ratio of 16α-hydroxyestrone/2-hydroxyestrone metabolites in MCF-7 human breast cancer cells, have led to the hypothesis that xenoestrogens are a preventable cause of breast cancer. More recent studies and analysis of organochlorine levels in breast cancer patients versus controls show that these contaminants are not elevated in the latter group. Moreover, occupational exposure to relatively high levels of PCBs and DDT/DDE are not associated with an increased incidence of breast cancer. A reexamination of the radiometric E₂ 2-hydroxylase assay in MCF-7 cells with diverse estrogens, antiestrogens, and carcinogens showed that the mammary carcinogen benzo[a]pyrene induced this response and the antiestrogen ICI 164,384 decreased E₂ 2-hydroxylase activity. Thus, E₂ 2-hydroxylase activity and the 16α-hydroxyestrone/2-hydroxyestrone metabolite ratio in MCF-7 cells does not predict xenoestrogens or mammary carcinogens.