Challenging the convictions of many advocates for patients, a large study has found no evidence that exposure to the chemicals DDT and PCB's increases the risk of breast cancer.
There has long been concern that certain chemicals, notably the pesticide DDT, which was banned in 1972, and the industrial chemicals known as polychlorinated biphenyls, or PCBs, banned in 1977, might have contributed to the slow rise in the incidence of breast cancer in this country.
The chemicals, which accumulate in body fat, can act like weak estrogens in the body. And the more estrogen a woman is exposed to, the greater her risk of breast cancer.
Previous, smaller studies led to contradictory results, and some had design flaws that made them less than definitive.
The new study, by Dr. David Hunter, an epidemiologist at the Harvard School of Public Health, and his colleagues, was larger and better designed than any before it. It involved nurses who agreed in 1976 to participate in the long-term study, in which their health would be monitored. In 1989 and 1990, 32,826 of them sent in samples of their blood, which was stored.
Hunter and his colleagues examined the levels of DDT and PCB's in the blood of 240 of those women who subsequently developed breast cancer and compared them with the levels in the blood of other study participants who were similar in every way but did not develop breast cancer.
The investigators found no relationship between the level of DDT and PCB's in women's blood and their likelihood of subsequently developing breast cancer.
The results, to be published on Thursday in The New England Journal of Medicine, came as a shock to some advocates for patients.
"I just find it very difficult to believe," said Geri Barish, president of 1 in 9: The Long Island Breast Cancer Action Coalition, based in East Meadow, N.Y. "I can't accept it at all."
A co-author of the study, Dr. Mary Wolff, a chemist at Mount Sinai School of Medicine in New York , said it was too soon to rule out the possibility of a link.
But some leading scientists who were not involved in the study said the results, along with those of several other studies, made it extremely unlikely that there was any merit to the notion that DDT and PCB's were linked to breast cancer.
Hunter's study was "pretty definitive," said Dr. Virginia Ernster, professor of epidemiology at Stanford University.
Dr. Shelia Zahm, deputy chief of the occupational epidemiology branch at the National Cancer Institute, said the new study was "certainly a strong piece of evidence against the hypothesis."
The hypothesis had been fueled by a small study in 1994 by Dr. Wolff. She measured levels of DDE, a metabolite of DDT, and of PCB's in the blood of 58 women with breast cancer and compared them with levels of the chemicals in the blood of women without cancer. The higher the level of DDE in her blood, the greater a woman's risk of breast cancer, Dr. Wolff found.
Her study was soon followed by larger studies, in Europe, Mexico and the United States, that failed to find such correlations. In the European study, the researchers even found that the higher the level of DDE in a woman's body, the lower her risk of breast cancer.
But, Dr. Zahm said, there were design problems in those studies. They were small, had too many subjects drop out or the researchers did not insist that the levels of DDT and PCB's be measured in the same year in all of the women, an important consideration since the levels of these chemicals fall every year as the body slowly rids itself of them.
And so, Dr. Zahm said, it remained possible that the negative results were spurious. Hunter, she added, had "a strong study design." And now, she concluded, the body of evidence that DDT and PCB's can cause breast cancer "is not very compelling."
Some scientists, like Dr. Bruce Ames, a biochemist who is director of environmental health science at the University of California at Berkeley, and Dr. Stephen Safe, a toxicologist at Texas A&M University in College Station, have been skeptical of the hypothesis from the beginning.
They noted that DDT and PCB's are very weak estrogens present in minuscule amounts in the body. Studies in which laboratory animals were given high doses of such compounds led to contradictory results: in some the compounds were found to caused breast cancer, in others they protected against it. Moreover, plants have so many naturally occurring estrogens and anti-estrogens that they might overwhelm any conceivable effects of environmental chemicals like DDT and PCB's.
For example, Safe said, the amount of biologically active plant estrogens in a single glass of red wine is 1,000 times greater than that of all the environmental chemicals that a person gets from pesticides in a day's food.
"And that's just in glass of wine, never mind beans, carrots, and all the other vegetables," he said.
Hunter said that perhaps it was time to question the assumption that much breast cancer is caused by unknown environmental agents. A recent study, for example, found that the high rate of breast cancer in the San Francisco Bay area can be completely attributed to known risk factors like a woman's age when she starts to menstruate, has a first child and when she begins menopause.
On the other hand, Hunter said, his new results by no means exonerated all environmental chemicals.
Dr. Zahm agreed. "Even if we suspect one chemical and the evidence doesn't bear it out, that doesn't negate the entire argument," she said.
In fact, said Dr. Wolff, who did the chemical analyses for Hunter's study, it does not even negate the DDT and PCB argument.
"I think it's premature" to abandon the DDT and PCB hypothesis, Dr. Wolff said. "It may be important in some groups of women and it may be not only how high the levels are but the time of life in which they occur. Maybe it's even different for different kinds of breast cancer, like premenopausal and postmenopausal."
Julia Brody, the executive director of the Silent Spring Institute in Newton, Mass., an advocacy group studying links between women's health and the environment, said the new study was "definitely not the last chapter."
After all, Ms. Brody said, "this is a study of two chemicals out of 80,000," in the environment.
Safe said those who believed in the hypothesis would always want "another study, another study."
"For advocates, it's never-ending," he said. "But for other people, there may be times when we want to spend our money on other things."
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