Organochlorine compounds and breast cancer risk

Abstract

A number of epidemiologic studies on organochlorines (OCs) and breast cancer risk have been published. The majority (n = 18) measured OCs in adipose tissue, primarily from mammary biopsies in cancer cases and controls with benign breast disease, and studied incident disease. Seven of these studies each included fewer than 50 cases and controls and had limited capacity for covariate adjustment. Eleven studies used serum samples collected from 6 months to 25 years prior to diagnosis. An additional 13 studies (2 with some overlap) used serum collected at or after diagnosis. Regardless of the medium used to measure OC levels, studies conducted to date do not provide consistent evidence that any of the OCs examined thus far play a role in the initial breast cancer risk. This paper provides a compound specific review with discussion of how the lack of evidence for adverse effects might be explained by factors related to study design, or by variation in risk across subgroups. The sum of the evidence does not implicate any OC compound as significantly related to risk of occurrence of breast cancer. The evidence base is greatest for dichlorodiphenyltrichloroethane (DDT) and dichlorodiphenyldichloroethylene (DDE). Limited research has been done on individual polychlorinated biphenyls (PCBs) and their isomers. The studies of OC exposure reflect current exposure levels of chemicals banned as long ago as 20 years. Although the information is extremely limited and not without major design flaws, the association between OCs and disease severity and progression is interesting and worthy of further examination. More studies are needed on OCs other than DDTs in developing countries where use is more recent or continuing, especially given that most estrogenic OCs are not persistent. It is possible that other pathways may be involved, including activity related to cytochrome P450 (CYP) and glutathione-S-transferase (GST); there is limited research to date on this hypothesis. In developed countries, a body mass index (BMI)/weight loss model may warrant further analysis, perhaps using existing data. OC exposures cannot reliably be related to trends in breast cancer incidence, as other known risk factors for breast cancer, such as childbearing and lactation, have changed along with OC residues during this timeframe. Changes in screening and treatment over time also complicate making such links. Ecologic data relating high-exposure countries to high breast cancer mortality rates do not suggest a strong link. Breast cancer rates are not generally higher in parts of the world with high DDE levels. Countries with relatively similar levels of PCBs, such as Great Britain and Japan, have very different breast cancer rates. As OCs are present in the environment as mixtures of correlated isomers and metabolites, it may be difficult to distinguish possible causal links from associations in which measured compounds are merely markers of other underlying exposures. For highly correlated compounds, traditional adjustment strategies may not be feasible. More complex analytical strategies may help to isolate potentially relevant isomers.