Breast cancer, oestrogens and environmental pollutants: a re-evaluation from a mixture perspective

The continuing rise in breast cancer incidence rates in almost all Western countries cannot be explained entirely in terms of known risk factors of the disease process. Additional determinants need to be examined, among them exposure to environmental pollutants. With the demonstration that elevated levels of endogenous sex hormones and the use of hormones for the relief of menopausal symptoms are associated with the disease, the oestrogen hypothesis of breast cancer has received further empirical support. This has led to heightened concerns about the possible involvement of oestrogen-like pollutants, such as p,p'-Dichlorodiphenyldichloroethane (DDE). Case-control studies assessing whether women with breast cancer have elevated burdens of p,p'-DDE have produced results not suggestive of a link with cancer risks. However, possible effects of p,p'-DDE and other pollutants cannot be seen in isolation from sex hormones also present in serum. In view of the low potency of p,p'-DDE, and its low levels in serum, it seems unlikely that the chemical on its own will add significantly to the action of sex hormones. However, chemical analyses show that numerous pollutants with oestrogen-like effect profiles can be found in human tissues. Thus, the oestrogen hypothesis of breast cancer should be extended to encompass the multitude of these agents. Viewed from such a perspective, a putative role of organochlorines and other agents in breast cancer should not be dismissed prematurely. Instead, breast cancer epidemiology should face the reality of combined exposures and should take account of recent evidence from in vitro models demonstrating that a large number of oestrogen-like pollutants, all present at low levels, can act together to add to the internal oestrogenic load.