Sorting through the arguments on breast screening.

VIEWS ON THE BENEFITS AND HARMS OF BREAST cancer screening are sharply polarized and increasingly vocal. Allegations of harming women are flung in both directions. The antiscreeners claim that benefit is minimal and overdiagnosis is so frequent that women are being subject to unnecessary interventions and treatment. The proscreeners claim that if the critics win the day, women will be deprived of the benefits that screening brings of early diagnosis and reductions in mortality from breast cancer. To those coming fresh to the argument, such disagreement seems surprising. Given the large body of evidence evaluating breast screening, it seems that the evidence would settle the issue. Such naivete does not allow for the fact that people interpret evidence and, indeed, influence its generation. Judgments often reflect more about starting assumptions than they do about the nature of the evidence. Into this somewhat raucous debate came the Independent UK Panel on Breast Screening. Given that views about the benefits and hazards of breast screening are so polarized that one only has to look at the author of an article to make a reasonable guess whether it will be pro or con, members of the breast screening panel were selected only if they had no prior publications on breast screening. It was hoped, therefore, that the only prior experiences shared by panel members were a desire to reach judgments based on sound science and to improve women’s health. Characteristically, the United Kingdom has a more cautious screening program than the United States. Breast cancer screening in the United Kingdom is recommended for women aged 50 through 70 years, every 3 years—the focus of the UK panel— rather than annual screening starting at age 40 years that is usual in the United States. The purpose of screening is to advance the timing of diagnosis and thereby improve prognosis. Even were screening not to alter the natural history of breast cancer, screening would lead to an apparent prolongation of the time between diagnosis and death—lead time. Therefore, the appropriate end point to evaluate the benefits of screening is mortality from breast cancer. In the panel’s judgment, the best evidence for the relative benefit of screening on mortality reduction is based on 11 randomized controlled trials (RCTs) of breast screening. Meta-analysis of these trials with 13 years of follow-up estimated a 20% reduction in breast cancer mortality among women invited for screening. The panel based its metaanalysis on data reported in a Cochrane review. The Cochrane review came to a similar estimate of relative reduction but, because of concerns about quality of some of the trials, reduced that estimate to 15%. The UK panel did not follow this procedure. Some have claimed that being in the screening group of a trial could be harmful. The correct end point, therefore, should be not breast cancer mortality but all-cause mortality. The power of the trials simply does not allow that: a 20% reduction in breast cancer mortality would translate into a 3% reduction in all cancer mortality and a 1.6% reduction in all-cause mortality. There has been a remarkable range in estimates of absolute benefit of screening, varying from 1 breast cancer death avoided for 2000 women invited to screening to 1 breast cancer death avoided for about 100 women screened, about a 20-fold difference. Major determinants of that large variation are the age of women screened and the durations of screening and follow-up. The panel applied the relative mortality reduction of 20% to achieve the observed cumulative absolute risk of breast cancer mortality over the ages of 55 through 79 years for women in the United Kingdom— assuming that women who began screening at 50 years would gain no benefit in the first 5 years but assuming that the mortality reduction would continue for 10 years after screening ended. This yielded the estimate that for every 235 women invited to screening, 1 breast cancer death would be prevented; correspondingly for 180 actually screened, 1 breast cancer death would be prevented. This seems relatively straightforward—randomized controlled trials show benefit. Yet questions have been raised about the internal and external validity of the trials. One argument against relying on the trials is that they were conducted 20 to 30 years ago and are therefore out of date. However, this criticism applies to all trials—their findings apply to the past. It is a judgment call whether conditions in