"The future will depend on our wisdom not to replace one poison with another."
Why?Despite mounting evidence of environmental causes for the breast cancer explosion, our scientific and political establishments have avoided investigating them. . .
The answer is worth knowing because, in this case, knowledge could be power--the power to redirect the nation's research priorities toward a theory that might save thousands of women.
by Michael Castleman
Scientists can't find what they don't look for--or what they ignore. Maybe that's why it's taken so long for the cancer research community to acknowledge that environmental pollutants may play a key role in the current breast cancer epidemic.
As long as 30 years ago, researchers showed that organochlorines, a family of compounds including the pesticide DDT and the industrial chemicals known as polychlorinated biphenyls (PCBs), could induce mammary tumors in laboratory animals, a red flag suggesting they might do the same in women. But for more than a decade, the cancer establishment--the National Cancer Institute, the American Cancer Society, and researchers at the nation's leading cancer research centers--largely ignored these findings.
Almost two decades ago, researchers noted that human breast tumors contain higher levels of these toxic chemicals than surrounding cancer-free breast tissue. Like the earlier studies, this research didn't prove that organochlorines cause human breast cancer, but it certainly raised the possibility and cried out for follow-up studies. Still, little attention was paid to the subject for another 15 years.
Finally in 1992, Frank Falck, M.D., Ph.D., then an assistant clinical professor in the department of surgery at the University of Connecticut School of Medicine, published an analysis of tissue samples from 40 women who had biopsies of suspicious breast lumps. Compared with lumps judged benign, those that were cancerous showed much higher levels of PCBs, DDT, and DDE (a DDT breakdown product).
Falck is an ophthalmologist-toxicologist, a cancer research outsider. He received no support from the National Cancer Institute or the American Cancer Society. But he had good timing. In recent years, breast cancer has become a major political issue. The nation's breast cancer activists--including an increasing number of researchers--have become fed up with the lack of progress against the disease, and several have been pursuing the possibility that organochlorines may be contributing to the epidemic. Last October, President Clinton announced that the National Institutes of Health's 1994 breast cancer research budget would be $300 million, a 44 percent increase over 1993. And in December, Secretary of Health and Human Services Donna Shalala convened the federal government's first breast cancer summit.
But the question remains: Why has it taken the cancer establishment three long decades to get serious about the possibility that pesticides and other environmental pollutants might cause breast cancer? The answer is worth knowing because, in this case, knowledge could be power--the power to redirect the nation's research priorities toward a theory that might save thousands of women's lives.
Breast cancer strikes 182,000 American women a year and kills more than 46,000. For the last 50 years, the breast cancer rate has been rising steadily and seemingly inexorably almost everywhere in the industrialized world. From 1973 to 1988, the U.S. breast cancer rate rose 26 percent. American women now have one chance in eight of developing breast cancer at some point in their lives.
Age is by far the most significant factor in the development of breast cancer. (About three-quarters of breast tumors are diagnosed in postmenopausal women.) But enormous controversy surrounds the causes of the disease. Its major risk factors seem to fall into three categories:
Organochlorines are organic compounds containing chlorine bonded to carbon. Virtually unknown in nature, they are primarily products or byproducts of the chemical industry. Their largest single use is in the manufacture of polyvinyl chloride (PVC) plastics, but they are also used in bleaching, disinfection, dry cleaning, fire prevention, refrigeration, and such pesticides as DDT and atrazine. One hundred seventy-seven different organochlorines have been found in human tissue and fluids. (Atrazine is still widely used. PCBs and DDT were banned years ago, but are still with us because they persist in the environment. An EPA report on dioxin, another highly toxic organochlorine, was scheduled for release in January but has been repeatedly postponed. It reportedly discloses that Americans have far higher levels of dioxin in their systems than was previously thought, and raises new questions about the chemical's relationship to breast cancer and other health problems.)
Most of the research linking organochlorines to breast cancer risk has focused on pesticides and PCBs because of their persistence in the environment and because toxicological data are available for them. Other organochlorines may be equally (or more) hazardous, but less is known about their effects on human beings.
Falck's 1992 study showing elevated levels of organochlorines in cancerous breast tumors set off a quiet flurry of scientific activity. One of Falck's co-authors, Mary Wolff, Ph.D., an associate professor in the division of environmental and occupational medicine at the Mount Sinai School of Medicine in New York, subsequently analyzed archived blood specimens taken from more than 14,000 women beginning in 1985. Samples from the 58 women later diagnosed with breast cancer were compared with blood samples from 171 similar women who remained cancer-free. Those with cancer showed significantly higher blood levels of DDE. Compared with women showing the least blood contamination, women with the most DDE had four times the breast cancer risk. Wolff's study is important not only because it was larger than previous ones, but also because it more accurately took into account the accepted risk factors for breast cancer.
Organochlorines may contribute to cancer risk in several ways. Some directly mutate genetic material; others enhance the carcinogenicity of other chemicals; and some mimic or disrupt natural hormones, including estrogen. DDT, DDE, and PCBs are all "xenoestrogens," which bind to the body's estrogen receptors. Xenoestrogens add important new dimensions to two of the accepted non-hereditary risk factors, estrogen exposure and dietary fat.
At least three researchers theorize that organochlorine pesticides and other xenoestrogens may significantly increase estrogen-related risk. Ana Soto, associate professor of anatomy and cellular biology at Tufts University, points out that the body eliminates natural estrogen cyclically, causing its levels to rise and fall. Many xenoestrogens, on the other hand, are not eliminated. Instead, they accumulate in fatty tissues such as those in the breast, where they remain even after menopause, when natural estrogen levels drop.
In addition, estrogen may be metabolized along two paths, "good" and "bad," which balance each other's effects. Xenoestrogens appear to block the good estrogen path, allowing bad metabolized estrogen to promote tumor growth. This theory has been advanced by Devra Lee Davis, Ph.D., M.P.H., a senior adviser to the Department of Health and Human Services' assistant secretary of health and the founding coordinator of the Breast Cancer Prevention Collaborative Research Group, and H. Leon Bradlow, director of biochemical endocrinology at Strang Cornell Cancer Research Laboratory. Metabolism of the natural estrogen known as estradiol, they explain, produces both 2-hydroxyestrone (2-OHE1 or "good" estrogen) and 16-alpha hydroxyestrone (16 alpha-OHE1, "bad" estrogen). The 16 alpha-OHE1 stimulates uncontrolled cell division, a trait associated with cancer. Xenoestrogens appear to block the 2-OHE1 pathway and increase levels of 16 alpha-OHE1.
Organochlorines also neatly explain the dietary fat controversy. Recall that migration studies suggest a link, but that most epidemiological investigations have come up empty. "It's not the amount of fat in a woman's diet," Falck explains. "It's what's in the fat. A woman may have a low-fat diet, but if the fat she consumes is contaminated with PCBs and DDE, bingo."
The effect of organochlorines in fat tissue is cumulative. "Food animals already have a toxic load accumulated in their own fat tissue," Falck continues, "and when women eat it, they get a much larger dose than they would from eating a vegetable containing some pesticide residue. The organochlorines become more concentrated as you move up the food chain."
An organochlorine link could also explain a recent drop in the breast cancer death rate in Israel. Between 1976 and 1986, breast cancer deaths (which had been continually rising for 25 years) dropped 8 percent.
Based on the commonly accepted risk factors, Israel's breast cancer death rate should, if anything, have increased. There was a strong trend toward delayed childbearing, and alcohol and fat consumption increased significantly.
Yet the death rate declined, and Jerome Westin and Elihu Richter, environmental medicine specialists at the Hebrew University-Hadassah School of Medicine in Jerusalem, offer a possible explanation: In 1978, Israel banned three organochlorine pesticides: DDT, alpha-benzene hexachloride (BHC), and gamma-benzene hexachloride (lindane). Before the ban these pesticides had been used in cowsheds. As a result, pesticide levels in Israeli milk soared up to 100 times those in the United States. Public outcry caused Israel to ban these pesticides, and within two years, DDT, BHC, and lindane levels in milk had dropped precipitously.
Critics have challenged Westin and Richter, saying that the drop in breast cancer deaths occurred "too soon" after the ban. Scientists commonly believe it takes about 20 years for carcinogens to do their dirty work, but the significant decline in Israel's breast cancer death rate was noticed only a few years after the organochlorine ban. Westin and Richter counter that organochlorines are "complete" carcinogens, which both initiate and promote tumor growth. Scientists believe that the withdrawal of complete carcinogens affects cancer statistics in just a few years.
Statistics represent human tragedies without the tears. Individual women with breast cancer almost never know whether environmental toxins played a role, even if they're certain they were exposed to them. In 1973, a few hundred pounds of polybrominated biphenyls (PBBs), close chemical relatives of PCBs, were accidentally mixed into animal feed in Michigan. More than 30,000 cattle, 1.5 million chickens, and thousands of sheep and hogs either died or had to be slaughtered, and some 9 million Michigan residents consumed PBB-tainted meat and dairy products. By 1976, 96 percent of Michigan's nursing mothers showed PBB in their breast milk.
Among those exposed to PBBs were my wife, Anne, and myself. We lived in Michigan at the time. About 15 years later, at the unusually young age of 38, Anne was diagnosed with breast cancer. Anne is a family physician and an assistant clinical professor at the University of California's San Francisco Medical Center. She's well informed about breast cancer risk factors, and after her diagnosis, she calculated that her risk was quite low, especially given her age. Could her case have been caused by PBB exposure?
"Not based on what we know now," says Harold Humphrey, Ph.D., a public health laboratory scientist for the Michigan Health Department's division of environmental risk assessment. Humphrey, who is directing the state's ongoing study of 4,000 farm family members who were heavily exposed to PBBs, says, "The people in our study definitely have PBBs in their fat stores, but so far--and we're 20 years out now--we've seen no unexpected increases in their cancer rate."
But other experts are less sure. Janette Sherman, M.D., a toxicologist in Alexandria, Va., and author of "Chemical Exposure and Disease," believes PBBs may have contributed significantly to Anne's cancer. "Anne has no family history, but she developed breast cancer at age 38. When a late-life cancer strikes unusually early in life, you have to suspect an environmental insult."
Anne and I both wonder if PBBs played a role in her cancer. Right now, no one knows for sure, but we believe more money should be invested in finding out. Unfortunately, that's easier said than done.
Despite the studies pointing to organochlorines as contributors to the breast cancer epidemic, their role--if any--is highly controversial. Scientists agree that occupational exposures to large amounts of toxic chemicals can cause cancer (and other illnesses). But here we're dealing with non-occupational exposures to amounts so minute that, until fairly recently, they could not even be measured.
"Low-level exposure to toxic chemicals has not been shown to pose a major cancer risk," says Clark Heath, M.D., chief epidemiologist at the American Cancer Society's headquarters in Atlanta. "The Israeli study is interesting, but not scientifically convincing. As for Falck's and Wolff's studies, they raise questions, but don't answer them."
The only way to answer these questions, however, is through additional research into toxic agents, and not enough is being done. In a presentation to the National Cancer Institute on behalf of 68 scientific experts, Samuel Epstein, M.D., a professor of occupational and environmental medicine at the University of Illinois School of Public Health in Chicago, charged that the agencies that fund cancer research are "continually . . . discounting or ignoring the causal role of avoidable exposures to industrial carcinogens."
The National Cancer Institute and the American Cancer Society bristle at this accusation, saying they spend millions of dollars a year on cancer prevention studies. "The problem," Epstein says, "is that most of what they call 'prevention' is actually basic science, research at the cellular and molecular levels. They devote so little to what I'd call prevention--for example, studies of the organochlorine pesticides--that I must conclude they are indifferent to it."
Why has the cancer establishment been so slow to consider the role of environmental factors in breast cancer? Several reasons:
It's appalling that research into environmental contributors currently represents only a trickle in the rising flood of breast cancer research. And it's maddening that breast cancer detection, diagnosis, and treatment have taken precedence over prevention. But there is some room for hope. Several investigators are already following up on the Falck and Wolff studies. Michigan's Harold Humphrey recently received a $100,000 federal grant, part of which will be used to analyze the PBB content in the breast tumors of farm women in his study.
In addition, last October, the House Subcommittee on Health and the Environment held hearings on organochlorine pesticides and xenoestrogens as causes of breast cancer, and heard testimony from several of the researchers interviewed for this article. The hearings began just six days after the release of a Greenpeace report that examined the organochlorine-breast cancer connection and called for an immediate phaseout of organochlorines. Devra Lee Davis has recommended that all chemicals released into the environment be screened for estrogenic activity, pointing out that although we have more data on the effects of organochlorines, other chemicals may pose equal health risks.
Individual women can take a few steps to reduce their personal breast cancer risks, but eliminating toxic breast hazards clearly requires political action. The wheels of both science and government grind slowly, but government is more publicly accountable, and it has tremendous influence over the funding of breast cancer research. "People need to become better informed about the link between toxic chemicals and breast cancer," says Falck. "Then they should start making noise."
Michael Castleman is a San Francisco medical writer. He won the 1993 American Medical Writers Association Rose Kushner Award for his coverage of breast cancer. Research assistance provided by Michelle Cottle. For a bibliography of the studies cited in this article, send a stamped, self-addressed envelope with $2 to Mother Jones, 731 Market St., Suite 600, San Francisco, CA 94103.
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