Pesticides
What are environmental estrogens?
Many people immediately think of synthetic chemicals when they read or hear about environmental risks for cancer. Such usage could easily lead to misinterpretations of what research reports actually say. In the research community, the word "environmental" refers to everything that is not part of the body and so includes everything that is eaten, drunk, breathed, or absorbed through the skin.
Environmental risks for breast cancer may arise from both natural and synthetic chemicals. Pesticides are among the environmental exposures that can cause cancer and other diseases. For example, severe problems of the central nervous system can be caused by acute exposure to high doses of some pesticides -- as might happen in industrial accidents -- or by mishandling of pesticides. But what about exposure to pesticides as they ordinarily occur in our environment?
Scientific research asks three questions to find out if a substance can cause breast cancer or disrupt the endocrine system. (1) Could the substance cause breast cancer, given what is known from biochemistry, test tube experiments, and the effects in laboratory animals? (2) Does the substance affect the risk of breast cancer in women? (3) If the substance does increase risk, by how much?
Natural versus synthetic pesticides in the diet Plants cannot run away from predators, which is why they have developed powerful chemical defenses over millions of years. We eat these detrimental substances (natural pesticides) in large quantities. Overall, the average American adult consumes about 1,500 mg of pesticides daily, of which only 0.09 mg are synthetic pesticides. Of these synthetic pesticides, 0.04 mg consist of chemicals that have shown no ability to induce cancer in cancer-prone rats or other rodent species. The remaining 0.05 mg have not been tested in animal feeding studies. The amount of natural pesticides in the diet is thus more than 10,000 times greater than that of synthetic pesticides. Several of the natural pesticides are known to cause cancer in high-dose feeding studies of rats and are therefore potential human carcinogens.
Natural pesticides have been identified in cruciferous vegetables (cabbage, cauliflower, brussel sprouts, etc.); mushrooms; celery; tea; fruit juices; apples, carrots, lettuce, potatoes; and many fruits. Highly mutagenic flavonoids are found in fruits, fruit juices, soy foods, many vegetables, red wines, and tea. Still, people who frequently eat any or all of these foods develop cancer less often than people who eat lower amounts. This occurs because plant foods also contain protective substances, including many anticarcinogens. Fortunately, protective substances found in plant foods outweigh the carcinogenic potential of their pesticides by a large margin.
Since all of the cumulative evidence shows a net reduction in rates of breast cancer among the women who eat the largest quantities of foods containing these substances, it is highly unlikely that pesticides act as a direct carcinogen that initiates breast cancer in humans. Recent research is examining the role of pesticides as potential promoters (rather than initiators) of cancer through their activity as weak estrogens.
What does the laboratory evidence show?
Several preliminary studies of the actions of some pesticides on individual cells within a test tube (in vitro) show estrogen-like activity. On this basis, some synthetic pesticides such as dichlorodiphenyltrichloroethane (DDT), endosulfan, chlordane, dieldrin, and toxaphene, and related chemicals including the polychlorinated biphenyls (PCBs) have been classified as environmental weak estrogens. This category also includes phytoestrogens such as the genistein in soy foods or the phenol resveratrol in red wine.
Most weak estrogens have been shown to increase the proliferation of breast cancer cells in vitro, particularly in the absence of stronger estrogens. Few studies have compared the relative estrogenic activity of various environmental estrogens, but the evidence to date shows that phytoestrogens are more efficient at stimulating estrogen responses than synthetic estrogens by a factor of 100:1. A mixture of organochlorines (a broad category of chlorinated hydrocarbons) in an amount equal to an average adult's daily consumption of pesticide residues on food showed estrogenic activity at a level equivalent to 1/1000th of a glass of red wine.
Because considerable evidence indicates that some pesticides, other chemicals, and natural/organic food products display estrogenic properties in test tubes, it is at least theoretically possible that weak estrogens could be associated with breast cancer. For this reason, several studies conducted among human populations have looked for such an association. The environmental estrogen genistein (contained in tofu and other soy products) appears to be connected with a reduced risk of breast cancer in observational studies, although there have been no intervention trials to prove that the weak-estrogen actions of genistein are causally related to the lower risk.
What is the evidence from human studies?
DDT and breast cancer The insecticide DDT was banned in the United States decades ago because of concerns about its long-term effects on the environment. Rachel Carson's book, "Silent Spring," provided powerful evidence that DDT affected reproductive patterns of birds and other animals. DDT is stored in fat and has a long half-life, so it remains present in detectable levels in blood, breast milk, and fat tissue samples.
Several moderately large studies have examined stored levels of DDT (or its breakdown product, DDE) in women with and without breast cancer. One study showed no difference in risk, and the other two studies reported a somewhat lower risk of breast cancer among the women with the highest levels of stored DDT; these differences, however, were not significant. Asian women in the California study had higher levels of stored DDE than Caucasian women, although the risk of breast cancer for Asian women is much lower than average. DDT continues to be used in warmer climates, where malaria is a major threat to health. A Mexican study reported that the one-third of women with the highest blood levels of DDT had a lower risk of breast cancer than the one-third with the lowest DDT levels; the difference was not statistically significant.
In the largest study of serum levels of DDT, the tested persons were followed for 10 years to compare rates of all cancers by blood levels of DDT. There were no differences. The authors reviewed all available published reports of DDT and cancer and concluded that DDT is not a carcinogen in humans.
Dioxin and breast cancer Dioxin is an herbicide and defoliant that was banned in 1983 in the United States. Dioxin levels persist for years in the environment, and in serum and fat tissue. Samples of fatty tissue show that stored dioxin levels have declined by 75% since 1975, a year of peak environmental exposure. High exposure to dioxin causes chloracne, a form of dermatitis (skin rash). There is evidence of a somewhat higher cancer risk among some pre-1983 chemical plant employees who received extremely high and frequent exposure to dioxin, with blood levels averaging more than 1,000 times those of people with lower or no occupational exposure. A major industrial accident in Seveso, Italy, in July of 1976 led to a community-wide dioxin contamination and the highest blood levels of dioxins ever reported in humans. However, after 20 years, the 2,200 women with the greatest exposure, and with the highest blood levels of dioxin, develop breast cancer less frequently than women in the unexposed control community, where blood samples contain little or no measurable dioxin. Since a potential association between dioxin and cancer rates is too small to be identified in studies of general human populations, data from high-dose animal experiments have been used to extrapolate the possible effect of dioxin and dioxin-like compounds (including some PCBs) on all forms of cancer. The hazard assessment figures project a maximum possible contribution of one per 10,000 of total human cancers, if such an association is present at all.
PCBs and breast cancer Polychlorinated biphenyls are not pesticides. They were used in the United States between 1929 and 1977 as coolants and lubricants in electrical equipment, because they are resistant to fire. They degrade very slowly in the environment and are stored in fatty tissue in animals, including humans. Because high-dose feeding of some PCBs to rats produced an excess of liver tumors, the manufacture of PCBs was banned in 1979. All three moderately large studies of PCB levels in the blood of breast cancer patients and controls revealed no differences in the risk of breast cancer.
Phytoestrogens Phytoestrogens are natural chemicals in plant foods that have estrogen-like effects in the body. This source accounts for more than 99.9% of environmental estrogen exposure in humans. In test tubes and in laboratory animals, different types of phytoestrogens can either suppress or increase the growth of breast cancer cells, promote cell proliferation that permits cancer growth, increase or reduce the total amount of estrogens circulating in the blood, or show opposite effects under different circumstances.
Soy foods are a rich source of several phytoestrogens. Researchers are attempting to discover if the higher consumption of soy foods by Asian women is one of the reasons for their lower risk of breast cancer. Several studies of the usual dietary intake of soy foods have shown that the women who eat soy foods most frequently develop breast cancer less often. Consumption patterns during childhood and the early teen years are believed to make the most difference in the risk of breast cancer. It is not certain which phytoestrogens, which other components of soy foods, or whether total consumption of more plant foods in general may contribute to the lower breast cancer risk. It is also uncertain if a particular phytoestrogen, or combination of phytoestrogens, would have a net effect of reducing or increasing the risk of breast cancer in adult women.
Other organochlorines and breast cancer One of the studies that examined blood levels of organochlorine compounds other than DDT and PCBs reported the pesticide dieldrin to be associated with the risk of breast risk. The 50% of women with the highest levels of dieldrin had twice the risk as the 25% with the lowest levels of dieldrin. Some news media reported that dieldrin, but not DDT or PCBs, was therefore associated with an increased risk of breast cancer. Because of the way these data were grouped and analyzed, it is likely that the results were due to chance. We will not know if exposure to dieldrin increases the risk of breast cancer until other independent studies are performed.
Combinations of chemicals at high exposure levels The long-term consequences of routine exposure to high doses of chemical carcinogens or endocrine disrupters are examined by looking at disease rates among occupational groups with different amounts of exposure to full-strength pesticides and related chemicals. Groups at the highest potential risk include farmers, professional pesticide applicators, and people who live in farming communities where large amounts of pesticides are used on a routine basis. Cancer rates among farmers have been measured in large studies conducted in Iowa, Minnesota, the central United States, 23 states as a group, the entire United States, and in other countries. In each study, men and women who farm have below-average rates of total cancers. One type of cancer, non-Hodgkin's lymphoma, may occur at elevated rates among farmers. There is no suggestion of an increased risk of breast cancer or other cancers of the reproductive system.
Among men and women who manufacture or apply pesticides on a regular basis, the risk of all cancers is the same as, or lower than, that for people with no occupational exposure to pesticides. The risk of some less common cancers (non-Hodgkin's lymphoma, multiple myeloma, and soft tissue sarcoma) appears to be elevated, although the difference in risk is not connected to exposure to any particular chemical. Use of pesticides before 1965, and without using masks or other protective garments, is associated with this elevated risk of total pesticide use. There is no difference in the risk of breast cancer or other cancers of the reproductive system according to history and intensity of pesticide use. A possible connection between non-Hodgkin's lymphoma or multiple myeloma and direct body contact with chemical carcinogens is supported by other lines of evidence. Women who have used black (not dark brown) permanent hair coloring for 20 or more years have a higher risk of these same specific cancers, although not for breast or reproductive cancers.
The risk of breast cancer for women who live on farms is the same as for women who do not. The risk for farm and non-farm residents of a Michigan community with the highest levels of pesticide use in the state is the same as for women in Michigan communities with no pesticide use.
How large is the potential risk of breast cancer from pesticides and environmental estrogens?
All studies of women with high occupational or accidental exposures to a variety of full-strength pesticides and related chemicals show no increased risk of breast cancer. The most likely interpretation of the findings is that there is no association in humans. A very small increase in risk could be ruled out only if even more studies involving millions of woman-years also showed no differences in risk at all.
Since the potential risk to women with direct and long-term exposure to full-strength pesticides and similar chemicals is too small to be detectable, then the risk to other women with exposures to microscopic quantities of pesticide residues on food products is so very much smaller that it could never be detected. For all practical purposes, there is no reason to consider these exposures as a contributor to the risk of breast cancer.
