Elsevier

The Lancet

Volume 355, Issue 9198, 8 January 2000, Pages 129-134
The Lancet

Public Health
Is screening for breast cancer with mammography justifiable?

https://doi.org/10.1016/S0140-6736(99)06065-1Get rights and content

Summary

Background

A 1999 study found no decrease in breast-cancer mortality in Sweden, where screening has been recommended since 1985. We therefore reviewed the methodological quality of the mammography trials and an influential Swedish meta-analysis, and did a meta-analysis ourselves.

Methods

We searched the Cochrane Library for trials and asked the investigators for further details. Meta-analyses were done with Review Manager (version 4.0).

Findings

Baseline imbalances were shown for six of the eight identified trials, and inconsistencies in the number of women randomised were found in four. The two adequately randomised trials found no effect of screening on breast-cancer mortality (pooled relative risk 1·04 [95% CI 0·84–1·27]) or on total mortality (0·99 [0·94–1·05]). The pooled relative risk for breast-cancer mortality for the other trials was 0·75 (0·67–0·83), which was significantly different (p=0·005) from that for the unbiased trials. The Swedish meta-analysis showed a decrease in breast-cancer mortality but also an increase in total mortality (1·06 [1·04–1·08]); this increase disappeared after adjustment for an imbalance in age.

Interpretation

Screening for breast cancer with mammography is unjustified. If the Swedish trials are judged to be unbiased, the data show that for every 1000 women screened biennially throughout 12 years, one breast-cancer death is avoided whereas the total number of deaths is increased by six. If the Swedish trials (apart from the Malmö trial) are judged to be blased, there is no reliable evidence that screening decreases breast-cancer mortality.

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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