Ramifications of screening for breast cancer: Overdiagnosis in the Malmö trial was considerably underestimated

EDITOR—Updated results from the Malmö mammography screening trial have suggested that screening caused an over-diagnosis of breast cancer of 10% in women aged 55-69 years at randomisation.1 The authors noted that evidence from randomised trials on the level of overdiagnosis was lacking. This is not correct. On the basis of data from the Malmö trial,2 and the two trials from Canada,3 we have previously estimated a level of overdiagnosis of 30% (mean follow-up 8.8 years and 7 years, respectively)4 and have also suggested an over-diagnosis of 33% in the other Swedish trials, based on number of cancers identified before the control group was screened.5

Zackrisson et al followed up the women for an additional 15 years after the trial ended and noted that they could have underestimated the level of overdiagnosis as some asymptomatic women in the control group received mammography. They did not quantify this, but in their original trial report2 they noted that 24% of a random sample of 500 women in the control group had undergone mammography during the trial period at least once. The authors now report1 that women aged 55-69 were never invited to screening after the trial ended, but it might be expected that many of them—after having belonged to the control group in a trial for so long—would have undergone mammography at least once subsequently.

If we assume (rather conservatively, compared with the 24% during the trial) that one quarter of the women had undergone mammography for the first time in their lives during these additional 15 years of follow-up then about half of the women in the control group received mammograms. This would change the estimated level of overdiagnosis from 10% to about 20%. If we assume that half of these women received mammograms after the trial the estimate becomes 40%. It is therefore essential that the authors provide data on use of mammography after the trial ended.

Because of the unavoidable screening in the control groups of the trials and the small sample size in the Malmö trial and therefore a wide confidence interval for the over-diagnosis estimate, it is necessary to look also at large and long term observational studies of the increase in the incidence of breast cancer after screening was introduced. Such data exist and they show an overdiagnosis of about 40-60%.5 These estimates could be inflated because of a possible concomitant increase in the use of hormone replacement therapy, which causes breast cancer, but this would only explain a minor part of the increases in the incidence of breast cancer. We therefore believe that our original estimate of 30% overdiagnosis with screening is still a very reasonable one.4