Evidence of geographic variation in incidence and mortality rates of breast cancer within the United States, the steady increase in incidence over time, and the identification of suspected breast cancer clusters have stimulated interest in the possibility that industrial chemicals or electromagnetic fields may be environmental risk factors for breast cancer. The experimental and epidemiologic evidence for associations of certain specific synthetic chemicals with breast cancer are considered in the following sections and have been comprehensively reviewed with detailed citations elsewhere.
Epidemiologic studies of breast cancer and environmental exposure to synthetic chemicals have concentrated on biologically persistent organochlorines. This class of compounds includes pesticides such as DDT, chlordane, hexachlorocyclohexane (HCH, lindane), hexachlorobenzene (HCB), kepone, and mirex; industrial chemicals such as polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs); and dioxins [polychlorinated dibenzofurans (PCDFs) and polychlorinated dibenzodioxins (PCDDs)], compounds produced as combustion by-products of PCBs or contaminants of pesticides.
Many of these chemicals are weak estrogens and are therefore hypothesized to increase breast cancer risk by mimicking endogenous estradiol. Furthermore, they are excreted in breast milk, which suggests that ductal and other cells in the breast are directly exposed. Other compounds, specifically the dioxins and some PCB congeners, exhibit antiestrogenic activity; therefore, despite the established carcinogenicity of dioxin at other anatomic sites in animal tests, they might be protective against breast cancer.
The organochlorines are highly lipophilic and resistant to metabolism. Thus, many of these compounds bioaccumulate in the food chain and persist in the body. These chemicals can be measured in breast milk, adipose tissue, and blood.Most of the epidemiologic literature on organochlorines focuses on DDT, DDE [1,1-dichloro-2,2,-bis(p-dichlorophenyl)ethylene, the main metabolite of DDT], and PCBs, because they are among the most persistent in humans.
The general population was thought to be exposed to these compounds predominantly through ingestion of fish, dairy products, and meat. Almost everyone in the United States has had some measurable exposure; however, the average body burden of some of these chemicals (e.g., DDT) has been decreasing with time since the cessation of their production in this country (1972 for DDT and 1977 for PCBs).
Although a positive correlation of age-specific breast cancer mortality rates in Israel with trends in DDT and other pesticide contamination in milk has been reported, estimates were based on only 2 years of data. When more extensive mortality and incidence data were analyzed, no association was observed.
In a study of PCB-contaminated fatty fish from the Baltic Sea, breast cancer rates among fishermen’s wives from the contaminated east coast were higher than rates among fishermen’s wives from the noncontaminated west coast (relative risk, 1.35; 95% confidence interval, 0.98 to 1.86).
However, there was no control for other known breast cancer risk factors. An accidental explosion in 1976 at a chemical plant near Seveso, Italy, provided the opportunity to evaluate exposure to high levels of dioxin. Breast cancer incidence during the decade after the accident in the areas closest to the accident was slightly but not significantly lower than expected.
Studies of occupational exposure to organochlorines have not supported an association with increased breast cancer risk. Fewer cases were observed than expected in studies of women occupationally exposed to phenoxy herbicides and PCBs. A twofold increase in breast cancer mortality was found in facilities with herbicide and dioxin exposures, but only 7% of the subjects worked in high-exposure areas. These studies are limited by difficulties of exposure assessment and the small numbers of women employed in the occupations with greatest exposure.