Objectives To assess the impact of population-based mammographic screening on breast cancer mortality in Europe, considering different methodologies and limitations of the data. Methods We conducted a systematic literature review of European trend studies (n ¼ 17), incidencebased mortality (IBM) studies (n ¼ 20) and case-control (CC) studies (n ¼ 8). Estimates of the reduction in breast cancer mortality for women invited versus not invited and/or for women screened versus not screened were obtained. The results of IBM studies and CC studies were each pooled using a random effects meta-analysis. Results Twelve of the 17 trend studies quantified the impact of population-based screening on breast cancer mortality. The estimated breast cancer mortality reductions ranged from 1% to 9% per year in studies reporting an annual percentage change, and from 28% to 36% in those comparing post-and prescreening periods. In the IBM studies, the pooled mortality reduction was 25% (relative risk [RR] 0.75, 95% confidence interval [CI] 0.69 -0.81) among invited women and 38% (RR 0.62, 95% CI 0.56 -0.69) among those actually screened. The corresponding pooled estimates from the CC studies were 31% (odds ratio [OR] 0.69, 95% CI 0.57 -0.83), and 48% (OR 0.52, 95% CI 0.42 -0.65) adjusted for self-selection. Conclusions Valid observational designs are those where sufficient longitudinal individual data are available, directly linking a woman's screening history to her cause of death. From such studies, the best 'European' estimate of breast cancer mortality reduction is 25 -31% for women invited for screening, and 38 -48% for women actually screened. Much of the current controversy on breast cancer screening is due to the use of inappropriate methodological approaches that are unable to capture the true effect of mammographic screening.

Objectives To evaluate the effect on breast cancer mortality during the first 10 years of the mammography service screening programme that was introduced in Copenhagen in 1991. Design Cohort study. Setting The mammography service screening programme in Copenhagen, Denmark. Participants All women ever invited to mammography screening in the first 10 years of the programme. Historical, national, and historical national control groups were used. Main outcome measures The main outcome measure was breast cancer mortality. We compared breast cancer mortality in the study group with rates in the control groups, adjusting for age, time period, and region. Results Breast cancer mortality in the screening period was reduced by 25% (relative risk 0.75, 95% confidence interval 0.63 to 0.89) compared with what we would expect in the absence of screening. For women actually participating in screening, breast cancer mortality was reduced by 37%. Conclusions In the Copenhagen programme, breast cancer mortality was reduced without severe negative side effects for the participants.

Objectives To estimate the impact of service mammography screening on breast cancer mortality using European incidence-based mortality (IBM) studies (or refined mortality studies). IBM studies include only breast cancer deaths occurring in women with breast cancer diagnosed after their first invitation to screening. Methods We conducted a literature review and identified 20 publications based on IBM studies. They were classified according to the method used for estimating the expected breast cancer mortality in the absence of screening: (1) women not yet invited; (2) historical data from the same region as well as from historical and current data from a region without screening; and (3) historical comparison group combined with data for non-participants. Results The estimated effect of mammography screening on breast cancer mortality varied across studies. The relative risks were 0.76 -0.81 in group 1; 0.75 -0.90 in group 2; and 0.52 -0.89 in group 3. Study databases overlapped in both Swedish and Finnish studies, adjustment for lead time was not optimal in all studies, and some studies had other methodological limitations. There was less variability in the relative risks after allowing for the methodological shortcomings. Conclusions Based on evidence from the most methodologically sound IBM studies, the most likely impact of European service mammography screening programmes was a breast cancer mortality reduction of 26% (95% confidence interval 13 -36%) among women invited for screening and followed up for 6-11 years.

Objective To estimate the cumulative risk of a false-positive screening result in European mammographic screening programmes, and examine the rates and procedures of further assessment. Methods A literature review was conducted to identify studies of the cumulative risk of a false-positive result in European screening programmes (390,000 women). We then examined aggregate data, cross-sectional information about further assessment procedures among women with positive results in 20 mammographic screening programmes from 17 countries (1.7 million initial screens, 5.9 million subsequent screens), collected by the European Network for Information on Cancer project (EUNICE). Results The estimated cumulative risk of a false-positive screening result in women aged 50-69 undergoing 10 biennial screening tests varied from 8% to 21% in the three studies examined (pooled estimate 19.7%). The cumulative risk of an invasive procedure with benign outcome ranged from 1.8% to 6.3% (pooled estimate 2.9%). The risk of undergoing surgical intervention with benign outcome was 0.9% (one study only). From the EUNICE project, the proportions of all screening examinations in the programmes resulting in needle biopsy were 2.2% and 1.1% for initial and subsequent screens, respectively, though the rates differed between countries; the corresponding rates of surgical interventions among women without breast cancer were 0.19% and 0.07%. Conclusion The specific investigative procedures following a recall should be considered when examining the cumulative risk of a false-positive screening result. Most women with a positive screening test undergo a non-invasive assessment procedure. Only a small proportion of recalled women undergo needle biopsy, and even fewer undergo surgical intervention.

Objective To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.Design Population based cohort study.Setting Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark.Participants 57 763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009. Main outcome measuresOverdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups. ResultsIn total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening. ConclusionsOn the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval −3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.

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An organized mammography screening program was gradually implemented in Norway during the period 1996-2004. Norwegian authorities have initiated an evaluation of the program. Our study focused on breast cancer mortality. Using Poisson regression, we compared the change in breast cancer mortality from before to during screening in four counties starting the program early controlling for change in breast cancer mortality during the same time in counties starting the program late. A follow-up model included death in all breast cancers diagnosed during the follow-up period. An evaluation model included only breast cancers diagnosed in ages where screening was offered. The study group had been invited for screening one to three times and followed for on average of 5.9 years. In the follow-up model, 314 breast cancer deaths were observed in the study group, and 523, 404 and 638, respectively, in the four control groups. The ratio between the changes in breast cancer mortality between early and late starting counties was 0.93 (95% confidence interval [CI] 0.77-1.12). In the evaluation model, this ratio was 0.89 (95% CI: 0.71-1.12). In Norway, where 40% of women used regular mammography prior to the program, the implementation of the organized mammography screening program was associated with a statistically nonsignificant decrease in breast cancer mortality of around 11%.In Norway, piloting of an organized mammography screening program started in four counties in 1996 offering biennial screening to women aged 50-69 years. From 1999 onward, the program was gradually implemented in the rest of Norway, becoming nationwide in 2004.The Norwegian program is currently being evaluated under the mandate of the Norwegian Research Council. As the purpose of mammography screening is to prevent death from breast cancer, determining the effect of screening on breast cancer mortality is an essential part of the evaluation. Ideally, our study should be carried out comparing women offered screening with women in an unexposed control group. In a nonrandomized setting, where all women are offered screening, this is a complicated task. The obvious possibilities are use of a historical or a regional control group. However, these control groups will also reflect historical trends or regional differences. To take account of this, a study design with three control groups consisting of women in the screening region prior to screening and women in the nonscreening regions both during and prior to screening 1 has been previously used for the evaluation of screening in Denmark. 2In addition to the nonrandomized setting, evaluation of the Norwegian program was complicated by the fact that regular mammography was widespread prior to the program3, 3 and that the implementation of screening coincided with a dramatic increase in hormone use.

The example of Norway illustrates that although monitoring of screening outcome is highly warranted, this may be seriously jeopardized if use of mammography examinations was widespread prior to implementation of an organized program.