Walter Schwartz

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.

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.

Effect of population-based screening on breast cancer mortality

Although the wider scientifi c community has long embraced the benefi ts of population-based breast screening, there seems to be an active anti-screening campaign orchestrated in part by members of the Nordic Cochrane Centre. These contrary views are based on erroneous interpretation of data from cancer registries and peerreviewed articles. Their specifi c aim seems to be to support a pre-existing opposition to all forms of screening. These individuals, making claims of poor methods, selectively discount overwhelming scientifi c evidence from numerous randomised trials in diff erent countries that organised screening reduces breast cancer mortality. They claim that the signifi cant decrease in breast cancer mortality achieved by screening is due to improvements in treatment alone, discounting the benefi ts of early detection. If true, this would imply that breast cancer is an exception among adenocarcinomas in that early detection does not improve prog nosis—a claim contrary to the evidence. For women with breast cancer, early detection also results in improved quality of life from less extensive surgical treatment. Women with screen-detected breast cancer in the UK have half the mastectomy rate of women with symptomatic cancers— ie, 27% versus 53%. Organised, high-quality breast screening is an important public health initiative by numerous governments worldwide. These policies are based on robust and extensive analysis of individualised patient data from scientifi c trials, with particular attention paid to the balance of potential benefi ts and harms. To imply that such an international action is mass misrepresentation, or that screening is done for the benefi t of self-interested professionals, is as perverse as it is unjustifi ed. Comprehensive guidelines deal with the entire screening process. Organisations responsible for screening programmes regularly review published evidence on the eff ects of mammographic screening, and also contradictory interpretations. We consider the interpretation by Jorgensen, Keen, and Gotzsche, of the balance of benefi ts and harms to be scientifi cally unsound. Women would be better served by focusing eff orts on how best, and not whether, to provide breast screening. The signatories below, charged with provision and implementation of breast screening in many diff erent countries, remain convinced that the scientifi c foundation for populationbased, quality-assured, organised breast screening is one of the major accomplishments of the translation of clinical cancer research into public health practice. Early detection, in combination with appropriate treatment, signifi cantly lowers breast cancer mortality and improves the life quality of patients with the disease.

Women's patterns of participation in mammography screening in Denmark

The objective of the study is to analyse individual women’s participation patterns in mammography screening in Denmark. The study is set in the capital of Copenhagen and the county of Fyn representing around 95,000 women aged 50–69. The Central Population Register (CPR) was used to define the total target group, and supply information on migrations and deaths. Invitation and participation data came from the mammography screening programmes in Copenhagen (1991–1999) and Fyn (1993–2001), containing personal identification number, data on invitation date, participation and examination date for each screening round. In Copenhagen the coverage went from 70.5% in the first round to 63.1% in the fourth round, and the equivalent data for Fyn is 84.6% in the first round and 82.8% in the fourth round. Of the women eligible for at least three invitation rounds, 52.6% in Copenhagen and 76.4% in Fyn were faithful users, i.e. had participated in all screenings they were invited to. The conclusion is that the programme participation rates tend to overestimate the protection of the individual women covered by the programme. Behind the urban–rural gradient in programme participation is an even greater gradient in programme protection.

Decline in breast cancer mortality: how much is attributable to screening?

Objectives When estimating the decline in breast cancer mortality attributable to screening, the challenge is to provide valid comparison groups and to distinguish the screening effect from other effects. In Funen, Denmark, multidisciplinary breast cancer management teams started before screening was introduced; both activities came later in the rest of Denmark. Because Denmark had national protocols for breast cancer treatment, but hardly any opportunistic screening, Funen formed a “natural experiment”, providing valid comparison groups and enabling the separation of the effect of screening from other factors. Methods Using Poisson regression we compared the observed breast cancer mortality rate in Funen after implementation of screening with the expected rate without screening. The latter was estimated from breast cancer mortality in the rest of Denmark controlled for historical differences between Funen/rest of Denmark. As multidisciplinary teams were introduced gradually in the rest of Denmark from 1994, the screening effect was slightly underestimated. Results Over 14 years, women targeted by screening in Funen experienced a 22% (95% confidence interval 11%–32%) reduction in breast cancer mortality associated with screening (a reduction in breast cancer mortality rate from 61 to 47 per 100,000). The estimated reduction for participants corrected for selection bias was 28% (13%–41%). Excluding deaths in breast cancer cases diagnosed after end of screening, these numbers became 26% and 31%, respectively. Conclusions There is additional benefit in reducing breast cancer mortality from the early detection of breast cancer through mammographic screening over and above the benefits arising from improvements in treatment alone.

Does educational level determine screening participation

The objective of this study was to test the hypothesis that nonparticipation in organized mammography screening is due to insufficient understanding of the information in the invitation letter by relating educational level to user pattern. Data from two Danish mammography screening programmes in Copenhagen, 1991–1999, and Funen, 1993–2001 were taken for this study. The Danish Central Population Register was used to define target groups; screened participation data were provided by the health authority, and data on highest obtained education came from Statistics Denmark. Data on all breast imaging in 2000 outside organized screening were provided by radiology clinics. Included were all women eligible for at least three screens, and participation was classified into four mutually exclusive user groups. Organized mammography screening programmes in Copenhagen and Funen, Denmark were used as field of this study. Main outcome measures were age-adjusted relative risks (RR) and 95% confidence intervals (CI) of ‘never use’ versus ‘always use’ of screening by educational level, using women with secretarial/sales education as baseline. The RR of ‘never use’ was 1.65 (95% CI: 1.37–1.99) in Copenhagen and 1.93 (95% CI: 1.42–2.62) in Funen for academics, 1.60 (95% CI: 1.48–1.73) in Copenhagen and 1.26 (95% CI: 1.14–1.39) Funen for women with lower primary educational level. Taking other breast imaging into account, the RR was 1.60 (95% CI: 1.32–1.95) for academics in Copenhagen, and 1.90 (95% CI: 1.75–2.07) for women with lower primary education. In conclusion, our results did not support the hypothesis that lack of understanding the information in the invitation letter explains nonparticipation. ‘Never use’ was not inversely associated with the level of education, but showed a U-shaped association, even when use of breast imaging outside organized screening was taken into account.

Seventeen-years overview of breast cancer inside and outside screening in Denmark.

Abstract Background. Long-term data on breast cancer detection in mammography screening programs are warranted to better understand the mechanisms by which screening changes the breast cancer pattern in the population. We aimed to analyze 17 years of breast cancer detection rates inside and outside screening in two Danish regions, emphasizing the influence of organizational differences of screening programs on the outcomes. Material and methods. We used data from two long-standing population-based mammography screening programs, Copenhagen and Fyn, in Denmark. Both programs offered biennial screening to women aged 50–69 years. We identified targeted, eligible, invited and participating women. We calculated screening detection and interval cancer rates for participants, and breast cancer incidence in non-screened women (= targeted women excluding participants) by biennial invitation rounds. Tumor characteristics were tabulated for each of the three groups of cancers. Results. Start of screening resulted in a prevalence peak in participants, followed by a decrease to a fairly stable detection rate in subsequent invitation rounds. A similar pattern was found for breast cancer incidence in non-screened women. In Fyn, non-screened women even had a higher rate than screening participants during the first three invitation rounds. The interval cancer rate was lower in Copenhagen than in Fyn, with an increase over time in Copenhagen, but not in Fyn. Screen-detected cancers showed tumor features related with a better prognosis than tumors detected otherwise, as more than 80% were smaller than 20 mm and estrogen receptor positive. Conclusion. Data from two long-standing population-based screening programs in Denmark illustrated that even if background breast cancer incidence and organization were rather similar, performance indicators of screening could be strongly influenced by inclusion criteria and participation rates. Detection rates should be interpreted with caution as they may be biased by selection into the screening population.

Type of hormone therapy and risk of misclassification at mammography screening

Objective: Current users of hormone therapy (HT) are known to have a lower accuracy of mammography screening than do never users. We studied whether the risk of misclassification depends on type of hormone, administration, regimen, and dose of the therapy. Methods: We linked data from mammography screening registers with drug prescription registers from Fyn, Denmark to identify current and never HT users among screening participants. We compared false-positive risks and interval cancer proportions between current users of different HT preparations, taking womens age, breast density, screen number, and age of comparison mammogram into account. Results: Estrogen therapy users had a significantly higher false-positive risk when the administration was by injection instead of oral (relative risk [RR], 2.37; 95% CI, 1.37-4.09). Women using sequential estrogen plus progestogen therapy had a significantly higher false-positive risk (RR, 1.94; 95% CI, 1.16-3.26) and a nonsignificantly higher interval cancer proportion (RR, 4.29; 95% CI, 0.69-26.53) when the administration of both hormones was transdermal instead of oral. Using tibolone instead of comparable hormones gave a nonsignificantly lower false-positive risk and a nonsignificantly higher interval cancer proportion. Conclusions: Our data showed increased risks of misclassification at mammography screening among women using estrogen injections or transdermal, sequential estrogen plus progestogen. Tibolone seems to offer no advantage regarding accuracy of screening mammography.

Existing data sources for clinical epidemiology: the Danish Quality Database of Mammography Screening

The Danish Quality Database of Mammography Screening (DKMS) was established in 2007, when screening was implemented on a nationwide basis and offered biennially to all Danish women aged 50–69 years. The primary aims of the database are to monitor and evaluate the quality of the screening program and – after years of follow-up – to evaluate the effect of nationwide screening on breast cancer-specific mortality. Here, we describe the database and present results for quality assurance from the first round of national screening. The steering committee for the DKMS defined eleven organizational and clinical quality indicators and standards to monitor the Danish breast cancer screening program. We calculated the relevant proportions and ratios with 95% confidence intervals for each quality indicator. All indicators were assessed on a national and regional level. Of 670,039 women invited for mammography, 518,823 (77.4%) participated. Seventy-one percent of the women received the result of their mammography examination within 10 days of screening, and 3% of the participants were recalled for further investigation. Among all detected cancers, 86% were invasive cancers, and the proportion of women with node negative cancer was 67%. There were 36% women with small cancers, and the ratio of surgery for benign lesions to malignant lesions was 1:6.3. A total of 80% of women with invasive cancers were treated with breast conserving therapy. Screening interval and interval cancers were not relevant in the first round, and data regarding radiation dose were not available at the time of evaluation. Overall, the quality indicators showed satisfactory quality in the first round of national breast cancer screening in Denmark. The DKMS is a potentially valuable tool for improving quality and conducting research in the field of breast cancer screening.