Sisse Helle Njor

The impact of mammographic screening on breast cancer mortality in Europe: a review of observational studies

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 = 17), incidence-based mortality (IBM) studies (n = 20) and case-control (CC) studies (n = 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 womans 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.

Breast cancer mortality in Copenhagen after introduction of mammography screening: cohort study

Abstract 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.

Breast cancer mortality in mammographic screening in Europe: a review of incidence-based mortality studies

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.

False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes

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.

The impact of mammographic screening on breast cancer mortality in Europe: a review of trend studies

Objective Analysing trends in population breast cancer mortality statistics appears a simple method of estimating the effectiveness of mammographic screening programmes. We reviewed such studies of population-based screening in Europe to assess their value. Methods A literature review identified 17 papers, of which 12 provided quantitative estimates of the impact of screening. Due to differences in comparisons and outcome measures, no pooled estimate of effectiveness was calculated. Results Comparisons included breast cancer mortality before and after the introduction of screening, trends in early and late starting areas and trends in age groups affected and unaffected by screening. Studies that calculated the percentage annual change after the start of screening found reductions of 1–9% per year (1%, 2.3–2.8% and 9% for those with adequate follow-up). Of studies that compared mortality in time periods before and after introduction of screening, three single country studies all had adequate follow-up and estimated mortality reductions ranging from 28% to 36%. Limitations of studies of population mortality rates include the inability to exclude deaths in women with breast cancer diagnosed before invitation to screening, diluting any observable impact of screening, and the gradual implementation of screening in a country or region. Conclusions Although analysing population breast cancer mortality rates over time can be a first step in examining changes following the introduction of screening, this method is of limited value for assessment of screening impact. Other methods and individual data are necessary to properly quantify the effect.

Socio-demographic determinants of participation in mammography screening

Our objective was to use individual data on socio‐demographic characteristics to identify predictors of participation in mammography screening and control to what extent they can explain the regional difference. We used data from mammography screening programmes in Copenhagen, 1991–1999, and Funen, 1993–2001, Denmark. Target groups were identified from the Population Register, screening data came from the health authority, and socio‐demographic data from Statistics Denmark. Included were women eligible for at least 3 screens. The crude RR of never use versus always use was 3.21 (95%CI, 3.07–3.35) for Copenhagen versus Funen, and the adjusted RR was 2.55 (95%CI, 2.43–2.67). The adjusted RR for never use among women without contact to a primary care physician was 2.50 (95% CI, 2.31–2.71) and 2.89 (95% CI, 2.66–3.14), and for women without dental care 2.94 (95% CI, 2.77–3.12) and 2.88 (95% CI, 2.68–3.10) for Copenhagen and Funen, respectively. Other important predictive factors for nonparticipation were not being married and not being Danish. In conclusion, to enhance participation in mammography screening programmes special attention needs to be given to women not using other primary health care services. All women in Copenhagen, irrespective of their socio‐demographic characteristics, had low participation. Screening programmes have to find ways to handle this urbanity factor.

Overdiagnosis in screening mammography in Denmark: population based cohort study

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 measures Overdiagnosis 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. Results In 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. Conclusions On 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.

Do nonattenders in mammography screening programmes seek mammography elsewhere

The objectives of our study were to analyse the use of diagnostic mammography among nonattenders and attenders in organised mammography screening in Denmark in 2000, to assess the contamination from organised screening of noninvited age groups and to measure the impact of local policy on opportunistic screening. Data on all diagnostic mammographies performed in Denmark in 2000 and data on women targeted by the 2 organised mammography screening programmes in Copenhagen and the county of Fyn were collected. All data were linked by the Danish personal identification number. Information on the official policy in 2000 with regard to opportunistic screening was collected from all counties. The proportion of women using diagnostic mammography was only 1–3% for both attenders and nonattenders in organised mammography screening, but it was significantly higher in Copenhagen than in Fyn, due to availability of mammography in private clinics. The proportion of women using diagnostic mammography varied from 1–4% across counties. The official policy on access to diagnostic mammography and contamination from organised mammography screening of adjacent age groups had no impact on the use. Instead, urbanisation was positively correlated with use of diagnostic mammography. In conclusion, our results clearly showed that nonattenders in organised mammography screening programmes do not seek mammography outside the programme. Since a positive policy toward opportunistic screening did not have any effect, our results add further evidence to existing knowledge that the only reasonable way to achieve high mammography coverage is through a well‐organised screening programme.

Breast cancer mortality in Norway after the introduction of mammography screening

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%.

Mammography activity in Norway 1983 to 2008.

Abstract Background. In Norway, an organized screening mammography program, the Norwegian Breast Cancer Screening Program (NBCSP) started in four counties in 1996 and became nationwide in 2004. We collected data on pre-program screening activity, and in view of this activity we evaluated the potential impact of the program on breast cancer mortality in Norway. Methods. We searched data sources on mammography activity in Norway. Three data sources reported on examination activity, and two on self-reported examinations. We aimed at calculating annual number of women examined by mammography from 1983 to 2008, and coverage rate in program and non-program Norwegian counties. Results. The annual number of women examined increased from 5000 in 1983 to 110 000 in 1993 to reach its maximum of 131 000 in 2002, excluding program examinations. The annual number of women examined in the organized program increased from 1996 to a steady state about 190 000 in 2004. Prior to start of the organized program, 40% of women in target age groups reported to have had mammography examination. During the years 1996–2002, 64% of first participants in the organized program reported to have been examined previously. Assuming that the Norwegian program would in absence of prior screening have decreased breast cancer mortality by 25%, and that the activity in- and outside the organized program were equally effective, the measured effect of the organized program would under actual circumstances be a reduction of 11%. Conclusion. 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.