Danish study questions value of mammography screening

A study published in the Jan. 8 Lancet that questions the value of screening mammography has ruffled some feathers in the mammography community, but appears unlikely to knock the procedure out of its position as a front-line defense against breast cancer.

The study, published by two researchers at Nordic Cochrane Centre in Copenhagen, Denmark, concludes that screening for breast cancer with mammography is unjustified, based on analysis of trials conducted since the 1960s. Professional and lobbying groups such as the American College of Radiology and the American Cancer Society, as well as individual clinicians around the world, vigorously contested the study’s conclusions and affirmed the value of mammography screening as a preventative tool against breast cancer mortality.

Researchers Dr. Peter Gøtzsche and Ole Olsen performed an analysis of eight mammography screening trials conducted with more than 500,000 women in North America and Europe over the past 35 years. Gøtzsche and Olsen asked investigators of these trials for details about the trials’ randomization method—the way patients were assigned to the screening versus control groups—and determined what basic criteria were used to establish study groups, such as age of the patient, presenting symptoms, family history of breast cancer, socioeconomic status, and previous examinations for breast cancer.

According to the study, inconsistencies in baseline criteria appeared in six of the eight trials, and discrepancies in the number of women randomized were found in four. Of the eight trials, Gøtzsche and Olsen found only two, one in Canada and one in Sweden, to be sufficiently randomized. They interpreted the results from these two trials as finding that screening had no effect on breast cancer mortality.

Mammography experts’ responses to the study were immediate. In an editorial published in the same issue of Lancet, Dr. Harry de Koning, member of the Netherlands’ National Evaluation Team for breast cancer screening and the department of health at Erasmus University Rotterdam, critiqued the study’s framework, arguing that, since Gøtzsche and Olsen have experience with meta-analyses of therapeutic trials, not screening trials, their conclusions are skewed. Screening trials have more variables than therapeutic trials, which the researchers perhaps did not take into account, de Koning said.

“In therapeutic trials participants have the disease, the main variables are treatment or no treatment and doses of treatment, study populations are much smaller than those in screening trials, and age differences are more crucial than in screening trials,” de Koning wrote. “In screening, the attendance rate, quality of the mammograms, accuracy in reading of the films, decisions for referral, and distribution of clinical stage before the start of the programme are all crucial factors influencing effect of screening.”

The authors were also criticized for their endorsement of the Canadian trial, which they lauded as an example of unbiased randomization. This trial, however, has long been considered to be the most poorly designed of the eight, according to Dr. Daniel Kopans, director of breast imaging at Massachusetts General Hospital.

“The credibility of (the authors’) analysis is lost in the fact that they emphasize that the Canadian study is an example of a properly performed and unbiased randomization, when the data clearly suggest that the Canadian randomization was likely significantly compromised,” Kopans said in a statement issued by the American College of Radiology. “Contrary to appropriate trial performance, the Canadian randomization was not blinded. All women were examined first, and they were assigned to the screened group or control group on open lists. At least for the women aged 40 to 49, this resulted in a ‘statistically significant’ excess of women with advanced breast cancer allocated to the screening arm.”

Mammography experts stressed that screening programs have reduced breast cancer mortality rates worldwide. In the U.S., mammography screening has been used since the early 1980s. Since 1990, mortality from breast cancer has dropped by 15% in the U.S., according to Joann Schellenbach, national media relations director of the American Cancer Society. Since screening for breast cancer was instituted, there has been a shift from a preponderance of stage II disease to the majority of cases being diagnosed before the cancer spreads to lymph nodes, Schellenbach said. In the 1970s, the average size of a tumor was 3.2 cm; now the average size is 2 cm.

One of clinicians’ concerns is that the study could confuse women and cause them to avoid screening mammography.

“(The study’s) analysis is inappropriate,” said Dr. David Dershaw, director of breast imaging at Memorial Sloan-Kettering Cancer Center and a member of the Society for Breast Imaging’s executive board. “It missed the point of the data that were included in these trials. The publication of this kind of flawed study is dangerous in that it could potentially discourage women from having a test that could save their lives.”

But in the U.K., where the study was published, it has had little impact, according to Dr. Alan Robin Muir Wilson, clinical director of breast services at Nottingham City Hospital.

“The screening units in the U.K. had very few inquiries from women and none have reported any change in screening. The media have forgotten the paper already,” Wilson said. “The Government Department of Health and our national screening office issued detailed statements supporting screening and even suggested extending the invitation range. Women appear to have been reassured.”

Similarly, Dr. Lázló Tabár, an internationally known mammography educator based in Sweden, had doubts the study would change anything.

“The scientific material published supporting screening is so monumental that some new guys on the block with their strange, unfounded ideas cannot disturb it,” he said.

CorrectionWe incorrectly stated the title of Dr. Daniel Kopans (SCAN 1/12/99). Dr. Kopans is director of breast imaging at Massachusetts General Hospital.