WASHINGTON — Women's health advocates expressed grave concern Thursday that participants in a new study aimed at preventing breast cancer are not being warned about the serious side effects of their drug therapy, including the possible development of blood clots and liver tumors.
Testimony about the inadequate warnings as well as risks of the drug tamoxifen came as a congressional panel examined the first large-scale breast cancer prevention study, announced earlier this year by the Cancer Institute.
Dr. Bernadine P. Healy, director of the National Institutes of Health, parent agency of the Cancer Institute, responded to critics by defending the projected five-year experiment involving 16,000 women 35 and older.
"We firmly believe there are more benefits than risks in the Breast Cancer Prevention Trial," Healy told the human resources and intergovernmental relations subcommittee of the House Government Operations Committee. She said that the $68-million study "is well-grounded, well-designed and tightly monitored."
She was responding to a panel of cancer experts and others who are familiar with the study who advised women to be cautious about participating.
Dr. Michael W. DeGregorio, professor of oncology at the University of Texas at San Antonio, said that stomach and liver tumors "may result from long-term use of tamoxifen" as envisioned in the study. He added that "many tamoxifen-related side effects are associated with chronic dosing for more than six months," including such lesser effects as hot flashes and menstrual irregularities.
Dr. Peter Greenwald, director of the Cancer Institute's prevention and control division, agreed that the study is controversial because it involves giving tamoxifen, a widely used cancer drug, to healthy women as a way to prevent the disease. But he said any side effects will be closely monitored. To date, more than 26,000 women have volunteered to take a daily dosage at 270 medical sites in the United States and Canada and more than 3,000 have begun doing so.
Greenwald said that 16,000 women selected as having a high risk of breast cancer will be divided randomly into two groups, one of which will be given 20 milligrams of tamoxifen daily. The other group will take a placebo, a pill with no medical value.
Neither the women nor the physicians will know who is taking which pill, a process known as double-blinding, authorities said. This allows researchers to see the possible benefits and side effects of the drug, with minimal influence from other factors.
Greenwald said that breast cancer, which will afflict one in every nine women, will be diagnosed in an estimated 180,000 women in the United States this year and that it will cause 46,000 deaths.
Healy said that new approaches to prevent cancer are crucial because "breast cancer is the leading cancer risk for women; it is an epidemic." She said that tamoxifen has been prescribed for cancer patients for more than 20 years "and there is evidence that women at risk can benefit from this trial." Healy added that the drug holds the promise of preventing 30% to 40% of breast cancer cases.
But Dr. Adriane Fugh-Berman, medical adviser to the National Women's Health Network of Washington, was among those who said that "the risks of tamoxifen have not been adequately described," including such side effects as dizziness, headaches, nausea and depression.
She told the subcommittee that "compared to preventive health measures such as vaccination . . . tamoxifen fails the more stringent standard of safety that must be applied when a medical intervention is unleashed on a healthy population."
Fugh-Berman said that she regrets "the medical profession has created a whole new category of 'patients' who have nothing wrong with them but a statistical possibility."
Women who run an above-average risk of breast cancer, authorities said, are those over 60, women whose menstrual periods began early and women with a family history of the disease.
Although Healy and Greenwald insisted that "informed consent" by all participants is an essential element of the program, Dr. Helen Rodriguez-Trias, president-elect of the American Public Health Assn., testified that "the central weakness (of the study) lies in a consent form that may not sufficiently emphasize the probable risks."
In addition, Rodriguez-Trias said that the 270 centers taking part in the program have offered varying degrees of instruction.
"To ensure truly informed consent," she said, "it is essential that the risks and benefits be clearly spelled out and thoroughly understood by the person imparting the information, as well as the person who will enter the study."
Rep. Donald M. Payne (D-N.J.), the subcommittee chairman, said it is "important to make sure that federally funded research protects the patients who participate from unnecessary risks and makes sure they are accurately informed of the likely risks and benefits."