Public HealthIs screening for breast cancer with mammography justifiable?
Introduction
After heated controversy, there now seems to be general acceptance that the benefit of screening for breast cancer with mammography has been well documented.1 Large randomised trials, including a total of half a million women, have been carried out in New York, USA;2 Edinburgh, Scotland;3 Canada;4, 5 and Malmö,6 Kopparberg,7 Östergötland,7 Stockholm,8 and Göteborg9 in Sweden. A meta-analysis of an update of the five Swedish trials, which used data from individual patients, was particularly influential. It showed that screening lowered mortality from breast cancer by 29% in women aged 50–69 years.10
The findings of a 1999 epidemiological study were therefore surprising. It found no decrease in breast-cancer mortality in Sweden,11 where screening has been recommended since 1985. The observed decrease in number of deaths from breast cancer was 0·8% (not significant), whereas the expected decrease was 11%. Although that study can be criticised,12, 13 it raises once again the issue of the reliability of the evidence that screening is effective.
We therefore reviewed the methodological quality of the mammography trials and the Swedish meta-analysis, and did a meta-analysis ourselves. We focused on the three most important sources of bias in randomised trials: suboptimum randomisation methods, lack of masking in outcome assessment, and exclusion after randomisation. We paid special attention to the quality of the randomisation, since bias caused by suboptimum randomisation methods can be larger14, 15 than the treatment effects that might be detected if a screening programme is beneficial.
Section snippets
Methods
We searched the Cochrane Library with the terms “breast-neoplasms/all” or “breast next cancer” and “screening” and “mammography” and extended the search with authors' names and other terms as appropriate to capture updates of the trials. When necessary, we asked the investigators for details about the randomisation method, in particular whether the assignment process was concealed so that no-one could foresee which assignment the next cluster or woman would get before actual recruitment. We
Randomisation methods and exclusions
In the New York trial, pairs of women were matched and the pairs were randomised.16 The allocation method is not clear—“every nth woman was placed in the study group, the paired (n+1) woman in the control group”.16 Because of the matching in pairs, the number of randomised women should be exactly the same in the study group and in the control group. This was not the case, and the number of women is unclear. It has been described as “about 31 000”,16 30 000,17 30 131,2 31 092,18 and 30 23919, 20
Discussion
The effect of screening programmes, if any, is small and the balance between beneficial and harmful effects is very delicate. It is therefore essential that such programmes are rigorously evaluated in properly randomised trials.
Unfortunately, the randomisation process failed to create similar groups in six of the eight trials of mammographic screening. Our analyses focused on age as a marker for imbalance, since this variable was the only baseline information we had available for the Swedish
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