The High Risk of Prevention; Tamoxifen on Trial

Article excerpt

Would you take a potentially dangerous drug in the hope of lowering your risk of developing a deadly disease? Last spring the National Cancer Institute of the National Institutes of Health began recruiting 16,000 healthy women to take part in a five-year, $60 million study to determine whether tamoxifen, a drug used with some success to treat breast cancer, can prevent the disease as well. To many, it seemed that the government was finally heeding advocates who have argued for years that it systematically neglects research into women's health, and women were quick to respond: In the first three days following announcement of the study, the N.C.I.'s hotline (1-800-4-CANCER) was jammed with almost 4,000 calls from would-be participants.

Their eagerness is understandable. Although the commonly cited statistic that one in nine women will contract breast cancer is misleading--it's based on a life expectancy of 85 years--the disease is a grave and, until recently, slighted public health concern. This year 180,000 women will be diagnosed with breast cancer; for about one-third of them, it will be fatal. Despite advances in early detection, medicine has made little progress in either treatment or prevention. The number of cases continues to rise, while the death rate has declined only minimally in the past fifty years. Although we know that certain factors increase one's chances of getting breast cancer--family history, early menarche, late menopause, not having a baby by age 30, obesity-70 percent of women with the disease have no known risk factors. No wonder women are frightened.

In this gloomy context, the Breast Cancer Prevention Trial, as the tamoxifen study is called, is being promoted as a bold new approach. And it is indeed something new in the world of public health research. Arthur Caplan, director of the Center for Biomedical Ethics, told a Congressional subcommittee looking into the tamoxifen trial in October that it will be the first major government study in which a substance known to have significant harmful effects will be given to healthy people to obtain information about its preventive properties. It is true that tamoxifen is an effective treatment (although not a cure) for breast cancer. It is also true that compared with other cancer therapies it looks as innocuous as a vitamin. But these are not the standards by which a preventive strategy ought to be judged. Unlike other public health measures, vaccination, fluoridation, iodized salt, encouragement of life-style changes--tamoxifen is a toxic substance inappropriate for dissemination to well people.

The premise that tamoxifen may prevent breast cancer is based on a 30-40 percent reduction in cancer of the second breast among women with breast cancer who have been treated with the drug. This success rate may, however, have no relevance for women who do not have cancer at all. The second breast of a woman with breast cancer has been exposed to exactly the same genetic, hormonal, dietary and toxic influences that the cancerous breast received. While our society commonly views women as collections of body parts, surely using one half of a woman's body as a "healthy control" for the other half is taking things a bit far.

Besides believing that treatment with tamoxifen will result in a reduction in breast cancer incidence, researchers also claim that the drug may fend off osteoporosis and heart disease. There is, however, skimpy evidence for either of these claims. Out of eight studies on tamoxifen and osteoporosis, five have found no beneficial effect on bone, and no study has shown a decreased rate of fractures.

The National Heart, Lung, and Blood Institute is contributing an additional $8 million to the Breast Cancer Prevention Trial in order to examine the effect of tamoxifen on the rate of cardiovascular disease. Only one of eight controlled trials has found a reduction in cardiac disease among women who were treated with tamoxifen, and even this finding is problematic because it is not clear that the control group and the intervention group were initially equivalent in terms of cardiovascular risk factors: Results would be affected if, for example, there were a preponderance of smokers or women with high blood pressure in the control group. …