Authors of Nordic mammo study no strangers to controversy

The debate over mammography got hotter last month with the publication of a study by Nordic researchers claiming there's no evidence that mammography screening reduces death rates. Some mammography advocates have taken issue with what they say is an antiscreening bias on the part of the research group.

Last month's study, published online March 24 in the British Medical Journal, is only the latest salvo questioning mammography's benefits from a group headed by Dr. Peter Gøtzsche of the Nordic Cochrane Centre in Copenhagen and colleagues from the Norwegian Institute of Public Health in Oslo.

In the new study, the group said reductions in breast cancer death rates in regions with screening were the same or actually smaller than in areas where no women were screened.

'Crude and insensitive?'

But the study obscures whatever benefit mammography might have because of its "crude and insensitive" methodology, according to a response submitted by Robert Smith, Ph.D., director of cancer screening at the American Cancer Society (ACS), and Dr. Stephen Duffy, professor of cancer screening at the Cancer Research U.K. Centre for Epidemiology, Mathematics, and Statistics in London. The response was published March 30 on the BMJ Web site.

"While we expect to see a range of benefits from mammography ... to argue that there is no benefit from modern mammography on the basis of such flawed methods means this paper feeds the media's hunger for controversy but contributes nothing of substance to the evidence or the ongoing debate," Smith and Duffy wrote.

Last month's research is only the latest antiscreening message from Gøtzsche's group, which has been producing papers questioning mammography's value for the past decade. For example, in a 2008 study, Dr. Per-Henrik Zahl, Ph.D., co-author on last month's BMJ study, published research claiming that many breast cancers would "spontaneously disappear" if not detected.

But the arguments Gøtzsche and Zahl offer are not scientifically justified, according to Dr. Daniel Kopans, professor of radiology at Harvard Medical School in Boston.

"[Gøtzsche and his colleagues] keep getting things published that don't have scientific structure to them," Kopans told AuntMinnie.com. "To take two different populations that aren't uniform and compare them doesn't work."

Kopans also posted a formal response to the study on the BMJ Web site. He wrote: "There is, clearly, a major problem with the peer review with regard to screening mammography. ... The recent article in the British Medical Journal by Jørgensen et al is another example of the failure of peer review that permitted the publication of a methodologically unsupportable analysis."

Indeed, just a week later, a U.K. study again confirmed screening mammography's value, finding that regular mammographic screening for breast cancer saves the lives of two women for every one who is given unnecessary treatment. The study, conducted by Dr. Stephen Duffy and colleagues, was published online March 31 in the Journal of Medical Screening.

Long-term skepticism

Gøtzsche's work has met with skepticism for years:

  • In 2000, Gøtzsche and Dr. Ole Olsen published a paper in The Lancet reporting that mammography screening is not justified (January 8, 2000, Vol. 355:9198, pp. 129-134). In response, Colin Begg, Ph.D., of the Memorial Sloan-Kettering Cancer Center in New York City called into question the publication process for the article.

    Begg wrote in The Oncologist that the "study was sponsored by the Cochrane Collaboration, but it transpires that other members of the Cochrane Breast Cancer Group had disagreed with the conclusions published in The Lancet. Subsequently, The Lancet took the extremely unusual step of essentially republishing the study, this time only displaying the results from the two trials that showed no benefit for mammography" (The Oncologist, June 2002, Vol. 7:3, pp. 174-176).

  • In 2003, Gøtzsche gave a lecture at Helsinki University Hospital called "Ten Years of Cochrane Collaboration," in which he argued that accepted beliefs should be questioned, using his work on breast cancer screening as an example. In 2004, Dr. Peter Dean of Turku University Central Hospital in Turku, Finland, wrote in an opinion published in the Journal of the American College of Radiology: "Gøtzsche's actions with respect to his work on breast cancer screening have not followed the Cochrane principles. His arguments, as presented in Helsinki, were based on his own review publications. Rather than refer to the published evidence ... he selectively misused the literature to further his arguments" (JACR, January 2004, Vol. 1:1, pp. 8-14).

  • On March 9, 2006, a Gøtzsche paper titled "Results of the Two-County trial of mammography screening are not compatible with contemporaneous official Swedish breast cancer statistics" was posted online ahead of print in the European Journal of Cancer. It was removed March 29 from the journal's Web site without any formal retraction, but was later published in the Danish Medical Bulletin, accompanied by a comment from Torben Schroeder, the publication's editor in chief. The comment said, in part, that "the process that led to removal of the accepted and published paper was unilateral," and that this was harmful, as "a withdrawn or removed paper invariably leaves ... an impression of scientific fraud."

Sour grapes?

Regarding criticism that the data used in the recent BMJ study are faulty, Gøtzsche responded via e-mail to AuntMinnie.com. "The criticism is unwarranted," he said.

He and study lead author Karsten Jørgensen took critics to task in their own response, also published online in BMJ on March 30. They responded in particular to criticism published in the journal by Professor Elsebeth Lynge, from the Institute of Public Health at the University of Copenhagen, and by Kopans:

"If there had been an effect of screening, we would have expected to see a widening gap in mortality rates over time between the screened and the nonscreened areas, just as in the randomised trials, but the two curves were parallel in the relevant time period, 1997 to 2006," Gøtzsche and Jørgensen said. "Kopans offers much criticism but little substance. He is cherry picking when he refers to the effect of mammography screening as being 'as high as 44%.' The best trials showed little or no effect, and the estimate from independent researchers is a 15% effect."

A problem of peer review?

The work by Gøtzsche and colleagues confounds real debate on the merits of mammography for breast cancer screening, according to Kopans.

"We should be able to have clear scientific discourse, not biased," Kopans told AuntMinnie.com. "I have no problem with debate. But the arguments against screening keep mutating as each version is proven wrong, while the arguments for screening remain unchanged."

Gøtzsche critics point to flaws in the peer review process, questioning why the studies are published at all. Yet peer review may not be the issue, according to Dr. Leonard Berlin, professor of radiology at Rush University Medical College in Chicago.

"I certainly believe in mammography as a screening tool," he told AuntMinnie.com. "But that doesn't mean Gøtzsche's articles shouldn't be read and absorbed. Is there controversy and disagreement over their research? Of course. But the truth about screening mammography is probably found somewhere in the middle [between Gøtzsche's arguments and his critics']."

By Kate Madden Yee
AuntMinnie.com staff writer
April 6, 2010

Related Reading

Mammography advocates weigh in on Nordic study, March 26, 2010

Breast cancer screens don't save lives: Nordic study, March 25, 2010

Norwegian mammo study claims to find cancer 'spontaneous regression,' November 24, 2008

Scandinavian studies take mammography to task once again, March 3, 2006

American Cancer Society blasts Danish mammography study, January 10, 2000

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