Updated breast screening study revives controversy

October 31, 2006

The validity of population-based breast screening has once again been called into question by the world’s media. The negative headlines have, ironically, been triggered by a report that finds mammography screening saves lives. But it is the concurrent likelihood of overdiagnosis that has captured journalists’ attention.

The validity of population-based breast screening has once again been called into question by the world's media. The negative headlines have, ironically, been triggered by a report that finds mammography screening saves lives. But it is the concurrent likelihood of overdiagnosis that has captured journalists' attention.

The flurry of media interest concerns a report by the Nordic Cochrane Center in Copenhagen analyzing the latest data from randomized clinical trials on mammography screening (Cochrane Database Syst Rev 2006;4:CD001877. DOI:10.1002/14651858.CD001877.pub2). Investigators identified seven completed trials involving over half a million women. They subsequently discounted data from one trial, because of undue bias.

Analysis of the remaining six trials showed that screening produced a 20% reduction in breast cancer mortality. The report's investigators argued that this figure would be reduced in practice, given that "the highest quality trials" demonstrated a lower effect. They settled on a relative risk reduction of 15% (absolute risk reduction 0.05%). The team additionally proposed an estimated 30% increase in overdiagnosis and overtreatment from screening (0.5% absolute risk increase).

The researchers concluded that for every 2000 women invited to join a screening program over 10 years, one would have her life prolonged. During this same period, however, another 10 healthy women would be diagnosed as having breast cancer and referred for unnecessary treatment. They estimated that more than 200 screening participants would experience "important psychological distress for many months" due to false-positive findings.

"The chance that a woman will benefit from attending screening is very small, and considerably smaller than the risk she will experience harm. It is thus not clear whether screening does more good than harm," the authors wrote.

The report's findings update a Cochrane Review published in 2001 that questioned the mortality benefit from screening altogether. Inclusion of the new data has now allowed investigators to draw a slightly more positive conclusion. But identification of the screening benefit was not entirely unexpected, according to statistician Dr. Peter Gøtzsche, the study's lead author.

"The new evidence we found merely consisted of data from longer follow-up of the old trials, so there were no surprises," Gøtzsche said. "No one knows for certain what the effect [of screening] really is. But as it is likely that there is a small effect; for example, some women get what could be called 'prophylactic mastectomy' because of overdiagnosis. We tried to estimate what that effect was."

Gøtzsche would like materials given to women invited for mammography screening to be updated. Participants cannot give truly informed consent without information on the harm screening can cause as well as the benefits, he said.

Many advocates for breast screening have endorsed Gøtzsche's call for openness, while stressing the merits of early cancer detection through screening.

"Certainly, women invited for screening should be made aware of both potential benefits and downsides such as possible initial misdiagnoses. But, overall, we continue to encourage U.K. women to participate in the NHS breast screening program," said Prof. John Toy, medical director of Cancer Research U.K.

Others are less convinced that more emphasis is needed on possible "overtreatment." Some cancers will never kill, while other potentially lethal lesions need to be detected even earlier, said Dr. Daniel Kopans, director of breast imaging at Massachusetts General Hospital. At the moment, women get treated according to the best available knowledge.

"The bottom line is that mammography screening prevents a significant number of women from dying from breast cancer. This is the best way that we have at the present moment to decrease deaths. Efforts are intensively trying to determine tailoring therapy, but the fact that treatment has not caught up with earlier detection is not the fault of mammography," he said.

The Cochrane report may be revised again in the future, but as yet no timetable for reappraisal has been set, according to Gøtzsche.

"We will update when it is relevant, but the data now published should be sufficient for rational decision making, so there is no hurry," he said.

For more information from the Diagnostic Imaging archives:

Conflicting breast screening reviews cause confusion

Danish mammography study causes a stir, but will probably have little impact

Laser system, dedicated breast scanner show promise as adjuncts

Screening mammography data provide yardstick to guide U.S. practices

Screening mammography: Practitioners consider Europe in the quest for better quality