Authors
Francine Laden et al., Journal of the National Cancer Institute 93(10):768-776 (2001).

1,1-Dichloro-2,2-bis(p-chlorophenyl)ethylene and polychlorinated biphenyls and breast cancer: combined analysis of five U.S. studies.

It is widely recognized that the incidence of breast cancer has been increasing over the past 50 years. However, the cause for this rise in breast cancer rates remains an enigma. It has been suggested that exposure to hormonally active agents (HAAs) in the environment may play a significant role. Consequently, the relationship between organochlorine exposure and breast cancer risk has been studied extensively. In particular, the association between exposure to organochlorine chemicals such as polychlorinated biphenyls (PCBs) and the major in vivo DDT metabolite, 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), persistent synthetic environmental toxicants that accumulate in body tissues, and breast cancer has been examined. The present study is important because it represents a combined analysis of five large U.S. studies that evaluated the association between breast cancer risk and organochlorine exposure. The studies were Western New York, Mount Sinai, Yale, Campaign Against Cancer and Stroke (CLUE I), and the Nurses' Health Study (NHS). All five studies concluded that there was no association overall; however, specific subgroup effects were observed. The authors of the present study reanalyzed the data by using a standardized approach to control for confounding factors and to assess effect modification.

The five studies included population-based and hospital-based case-control and nested case-control designs. In total, the studies comprised 1400 breast cancer patients and 1642 control subjects and the majority of the participants were postmenopausal. The combined evidence reported in this study does not support the hypothesis that elevated plasma or serum concentrations of PCB and DDE increases the risk of breast cancer. However, limitations do exist in combining studies with different designs. Yale analyzed the lipid-adjusted levels of PCB and DDE using a gravimetric determination whereas the other studies calculated total lipids from total cholesterol and triglycerides. These methods may yield different values. In addition, time of blood collection and location of participant residence differed between studies and may have influenced the observed absolute values. Furthermore, plasma and serum measurements were taken more than 10 years after the ban of these chemicals in the United States. Because of the long half-lives of these compounds, the observed levels were predicted to be indicative of past exposures. Although PCB and DDE are the most persistent and most easily detectable organochlorines, they are not necessarily the most toxic. Also, PCB congener concentrations in breast tissue are only weakly correlated with levels in blood; reliance on blood indices alone would substantially misclassify women's exposures at the tissue level, likely causing an underestimation of any association between PCBs and breast cancer. The present study does not rule out the possibility that these toxicants or other hormonally active agents in the environment may be associated with breast cancer risk.