David Cohen, M.D.·Published 6 June 2008·10 min read
Key points
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.
Organochlorines Epidemiologic studies of breast cancer and environmental exposure to synthetic chemicals have concentrated on biologically persistent organochlorines.
Many of these chemicals are weak estrogens and are therefore hypothesized to increase breast cancer risk by mimicking endogenous estradiol.
The organochlorines are highly lipophilic and resistant to metabolism.
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.
Organochlorines 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).
Written and revised by
David Cohen, M.D.
Our doctors write and review articles for accuracy and keep them up to date.
health.am provides general information, not medical advice. Always consult a qualified health professional about your own health.
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.{pagebreak}
The results of small case control studies of organochlorine levels and breast cancer risk have been mixed. In a large European case control study (265 cases), a significant inverse relationship between levels of adipose DDE and risk of breast cancer was observed after controlling for known breast cancer risk factors; the authors did not evaluate PCBs.
In a case control study in Buffalo, New York, lipid-adjusted serum levels of DDE, HCB, Mirex, and total PCBs were evaluated among 154 incident breast cancer cases and 192 community controls. No evidence was seen of a positive association between levels of any of these compounds and breast cancer risk, with the possible exception of the less-chlorinated PCBs. Lopez-Carrillo et al. analyzed serum DDE levels in a case control study in Mexico, where the pesticide DDT is still in use. Serum DDE levels were not associated with risk of breast cancer. In one small study, however, contrary to expectation, the levels of octachlorinated dibenzo-p-dioxin (OCDD) were slightly elevated in the cancer cases, although no differences were observed for six other polychlorinated dibenzo-p-dioxin isomers.
Three prospective studies have used stored blood samples collected before diagnosis to evaluate the relationship between DDE and total PCBs, and breast cancer. In a cohort of 14,290 women in New York City (80% of whom were white), levels in sera from 58 women diagnosed with breast cancer within 1 to 6 months of blood collection were compared with levels among 171 controls. After adjusting for known risk factors, the odds ratio for women in the tenth decile of DDE levels compared with those in the first was 4.08 (95% confidence interval, 1.49 to 11.20), and the positive trend was statistically significant.
{embed="ref/stat-menu-br-cancer"}
The equivalent odds ratio associated with PCB level was not statistically significant. In a prospective study of 57,040 San Francisco Bay area women who had provided blood in the late 1960s, when DDT and PCBs were still in production, 50 white women, 50 African-American women, and 50 Asian-American women with breast cancer occurring after blood draw and before 1991 were selected and compared with 150 control women matched for age and ethnicity. Risk of breast cancer was not associated with either DDE or PCB level when all ethnic groups were combined, although nonsignificant elevated risks were observed for DDE for African-Americans and whites. Among 236 women with breast cancer and their matched controls in the Nurses' Health Study, no evidence was found of a positive association between breast cancer and either DDE or PCBs.
The multivariate relative risks for women in the highest quintile compared with women in the lowest were 0.72 (95% confidence interval, 0.4 to 1.4) for DDE and 0.66 (95% confidence interval, 0.32 to 1.37) for PCBs. For women in the highest quintiles of both DDE and PCB levels, the relative risk was 0.43 (95% confidence interval, 0.13 to 1.44) for joint exposure.
In summary, most large studies have not found evidence of increased breast cancer risk associated with blood levels of DDE or total PCBs; however, a small effect will always be difficult to exclude. All available studies address exposure to organochlorines in the decade or two before enrollment; it will be ery difficult to obtain data to address the hypothesis that childhood or even in utero exposure is associated with breast cancer risk 50 or more years afterward. Nonetheless, organochlorines appear unlikely to be major breast cancer risk factors or the explanation for rising breast cancer rates.
Electromagnetic Fields Electromagnetic fields (EMFs) have been proposed to alter breast cancer risk, perhaps by altering melatonin secretion by the pineal gland. Although animal evidence is suggestive, few data address the relationship of melatonin levels to human breast cancer risk. Exposure to light at night has been shown to suppress melatonin secretion, and in some studies breast cancer risk has been lower among blindwomen.
Gathering high-quality epidemiologic data on EMF and nocturnal light exposure is challenging, and these questions are unlikely to be resolved definitively in the near future. Evidence of an elevated risk of male breast cancer associated with presumed occupational EMF exposure based on job title has been observed in some studies, but these results are based on small numbers of cases. No evidence of an increased risk of breast cancer was observed in the studies that also included female employees.
In case control studies designed specifically to study occupational exposure to EMF and breast cancer in women, small increases in risk have been inconsistently observed. However, in those studies, misclassification of exposure is a major concern. Because classifications are based on subjects' "usual" occupation, often obtained from death certificates, duration of exposure and personal work tasks could not be accounted for in most of the studies, and adjustment for known breast cancer risk factors was limited or entirely absent.
The general population is exposed to EMFs primarily from power lines, transformer substations, and electrical appliance use. In an initial 1987 study of mortality from all cancer subtypes and residential wiring configurations, a statistically significant elevation in female breast cancer incidence was associated with magnitude of exposure at the current residence.
Other studies in Britain, the Netherlands, and Taiwan, however, did not observe an association between female breast cancer deaths and residence in the vicinity of electricity transmission facilities. Again, these studies are limited by the indirect methods used to assess EMF exposure.
Use of electric blankets (produced before 1990) throughout the night approximately doubles an individual's average exposure to EMFs, because the blanket is placed close to the body. In one case control study, the use of electric blankets continuously throughout the night was associated with marginally significant increases for breast cancer in postmenopausal women (odds ratio, 1.46; 95% confidence interval, 0.96 to 2.20) and for premenopausal women (odds ratio, 1.43; 95% confidence interval, 0.94 to 2.17).
In a large case control study of breast cancer in women younger than age 55 years, however, no association was seen. Additional studies of electric blanket exposure and other residential exposures to EMFs and breast cancer risk are ongoing, but the biological plausibility and epidemiologic support for an important relation between EMF exposure and breast cancer risk are weak.{pagebreak}
Active and Passive Smoking The relationship between active cigarette smoking and risk of breast cancer has been extensively evaluated in both case control and cohort studies; collectively, the data provide strong evidence against any major overall relationship. Initiation of smoking early in adolescence, when breast tissue may be maximally sensitive to carcinogenic influences, has been associated with an increased risk in a large case control study. However, in the largest case control study to date, no association with smoking at an early age was observed.
Passive smoking has been suggested to be an important risk for breast cancer, in part because sidestream smoke contains more carcinogenic activity per milligram than mainstream smoke. In a cohort study of cancer mortality among Japanese women exposed to passive smoke at home, a slight and insignificant risk elevation was seen (crude relative risk, 1.3; 95% confidence interval, 0.8 to 2.0). In several case control studies, increases in risk of breast cancer have been seen, but usually without evidence of a dose response.
Despite these positive associations, the absence of an effect of heavy smoking for decades is difficult to reconcile with an effect of exposure to much lower amounts of environmental smoke. A likely explanation for the positive association seen in case control studies is methodologic bias related to the selection of controls or the retrospective recall of exposure to passive smoke. However, data from large prospective studies is required to resolve the issue.
{embed="ref/stat-menu-br-cancer"}
Silicone Breast Implants Most studies examining the relation of silicone breast implants to breast cancer risk have actually reported lower rates of breast cancer among women with implants; thus, a direct association between silicone breast implants and the occurrence of breast cancer is unlikely.
Summary of Evidence on Environmental Pollution and Breast Cancer Risk In general, evidence does not support any substantial relationship between exposure to humanmade chemicals or electrical fields in the environment and breast cancer risk. The most recent evidence in prospective analyses does not support an association between exposure to organochlorines and breast cancer risk.
Although occupational studies of EMF exposure have been inconclusive, residential studies imply that no risk is associated with overhead power lines. Measurable increases in breast cancer risk due to passive smoke seem implausible because of the lack of effect of active smoking, but prospective data are needed.
Although other environmental exposures that have not been identified may warrant evaluation, with the exception of ionizing radiation, no environmental exposure can be confidently labeled as a cause of breast cancer.
Walter C. Willett, Beverly Rockhill, Susan E. Hankinson, David J. Hunter and Graham A. Colditz
W. C. Willett: Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts B. Rockhill: Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts S. E. Hankinson: Departments of Medicine and Epidemiology, Harvard Medical School and Harvard School of Public Health, Boston Massachusetts D. J. Hunter: Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, Massachussetts G. A. Colditz: Department of Medicine, Harvard Medical School, Boston, Massachussetts
News
News
News
