Mireille J. M. Broeders

Initiation of population-based mammography screening in Dutch municipalities and effect on breast-cancer mortality: a systematic review.

BACKGROUND More than a decade ago, a mammography screening programme for women aged 50-69 years was initiated in the Netherlands. Our aim was to assess the effect of this programme on breast-cancer mortality rates. METHODS We examined data for 27948 women who died of breast-cancer aged 55-74 years between 1980 and 1999 (30560 cases until 2001). We grouped individuals into 93 clusters, depending on where they lived, and analysed data by use of national population statistics. We analysed time trends in breast-cancer mortality, adjusting for gradual implementations at municipality level, taking as year 0 the month and year in which screening began in a particular municipality. We used a Poisson regression model to estimate the time at which the trend started to turn. We assessed indirectly whether this turning point was related to initiation of screening or adjuvant systemic therapy in four clusters defined according to when screening was implemented. FINDINGS Compared with rates in 1986-88, breast-cancer mortality rates in women aged 55-74 years fell significantly in 1997 and subsequent years as predicted, reaching -19.9% in 2001. Mortality rates had been increasing by an annual 0.3% until screening was introduced; thereafter we noted a decline of 1.7% per year (95% CI 2.39-0.96) in women aged 55-74 years and of 1.2% in those aged 45-54 (2.40 to 0.07). The turning point in mortality trends arose at around year 0. Adjuvant systemic therapy is unlikely to be the cause of this turning point, since the mortality rates continued to rise up to 1 year after implementation in municipalities where screening began after 1995. INTERPRETATION Routine mammography screening can reduce breast-cancer mortality rates in women aged 55-74 years.

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 Screening Results 5 Years after Introduction of Digital Mammography in a Population-based Screening Program

PURPOSE To compare full-field digital mammography (FFDM) using computer-aided diagnosis (CAD) with screen-film mammography (SFM) in a population-based breast cancer screening program for initial and subsequent screening examinations. MATERIALS AND METHODS The study was approved by the regional medical ethics review board. Informed consent was not required. In a breast cancer screening facility, two of seven conventional mammography units were replaced with FFDM units. Digital mammograms were interpreted by using soft-copy reading with CAD. The same team of radiologists was involved in the double reading of FFDM and SFM images, with differences of opinion resolved in consensus. After 5 years, screening outcomes obtained with both modalities were compared for initial and subsequent screening examination findings. RESULTS A total of 367,600 screening examinations were performed, of which 56,518 were digital. Breast cancer was detected in 1927 women (317 with FFDM). At initial screenings, the cancer detection rate was .77% with FFDM and .62% with SFM. At subsequent screenings, detection rates were .55% and .49%, respectively. Differences were not statistically significant. Recalls based on microcalcifications alone doubled with FFDM. A significant increase in the detection of ductal carcinoma in situ was found with FFDM (P < .01). The fraction of invasive cancers with microcalcifications as the only sign of malignancy increased significantly, from 8.1% to 15.8% (P < .001). Recall rates were significantly higher with FFDM in the initial round (4.4% vs 2.3%, P < .001) and in the subsequent round (1.7% vs 1.2%, P < .001). CONCLUSION With the FFDM-CAD combination, detection performance is at least as good as that with SFM. The detection of ductal carcinoma in situ and microcalcification clusters improved with FFDM using CAD, while the recall rate increased.

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.

Comparison of Digital Screening Mammography and Screen-Film Mammography in the Early Detection of Clinically Relevant Cancers: A Multicenter Study

PURPOSE To compare screen-film mammography with digital mammography in a breast cancer screening program, with a focus on the clinical relevance of detected cancers. MATERIALS AND METHODS The study was approved by the regional medical ethics review board. Informed consent was not required. Before the nationwide transition to digital mammography in the Dutch biennial screening program, the performance of digital mammography was studied in three screening regions. For initial screening examinations, mediolateral oblique and craniocaudal views were obtained of each breast. In subsequent examinations, the mediolateral oblique view was standard. A craniocaudal view was added if indicated. Screening outcomes obtained with screen-film mammography and digital mammography, including radiologic and pathologic characteristics, were compared for initial and subsequent examinations. RESULTS A total of 1,198,493 screening examinations were performed between 2003 and 2007. Recall was indicated in 18 896 cases (screen-film mammography: 2.6% at initial examinations, 1.3% at subsequent examinations; digital mammography: 4.4% at initial examinations, 2.1% at subsequent examinations; P < .001 for both). Breast cancer was diagnosed in 6410 women (detection rate per 1000 women with screen-film mammography: 5.6 at initial examinations, 5.2 at subsequent examinations; detection rate per 1000 women with digital mammography: 6.8 at initial examinations, 6.1 at subsequent examinations; P = .02 and P < .001, respectively). Digital mammography depicted significantly more ductal carcinoma in situ (DCIS) lesions, irrespective of screening round. Invasive carcinoma was detected significantly more often in subsequent examinations, particularly when associated with microcalcifications (P = .047). The distribution of the histopathologic differentiation grades for DCIS and invasive carcinoma were similar with both modalities. However, with digital mammography more high-grade DCIS lesions were detected at subsequent examinations (P = .013). CONCLUSION In a population-based breast screening program, the performance of digital mammography in the detection of DCIS and invasive carcinoma was substantially better than that of screen-film mammography. There is no sign of an increase in detection of low-grade DCIS lesions-indicative of possible overdiagnosis-with digital breast cancer screening. Rather, digital mammography appears to add to the detection of high-grade DCIS.

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.

Mammography Screening and Risk of Breast Cancer Death: A Population-Based Case–Control Study

Background: Because the efficacy of mammography screening had been shown in randomized controlled trials, the focus has turned on its effectiveness within the daily practice. Using individual data of women invited to screening, we conducted a case–control study to assess the effectiveness of the Dutch population–based program of mammography screening. Methods: Cases were women who died from breast cancer between 1995 and 2003 and were closely matched to five controls on year of birth, year of first invitation, and number of invitations before cases diagnosis. ORs and 95% confidence intervals (CI) for the association between attending either of three screening examinations prior to diagnosis and the risk of breast cancer death were calculated using conditional logistic regression and corrected for self-selection bias. Results: We included 755 cases and 3,739 matched controls. Among the cases, 29.8% was screen-detected, 34.3% interval-detected, and 35.9% never-screened. About 29.5% of the never-screened cases had stage IV tumor compared with 5.3% of the screen-detected and 15.1% of the interval-detected cases. The OR (95% CIs), all ages (49–75 years), was 0.51 (0.40–0.66) and for the age groups 50–69, 50–75, and 70–75 years were 0.61 (0.47–0.79), 0.52 (CI 0.41–0.67), and 0.16 (0.09–0.29), respectively. Conclusion: The study provides evidence for a beneficial effect of early detection by mammography screening in reducing the risk of breast cancer death among women invited to and who attended the screening. Impact: This is the first case–control study that accurately accounts for equal screening opportunity for both cases and matched controls by number of invitations before cases diagnosis. Cancer Epidemiol Biomarkers Prev; 21(1); 66–73. ©2011 AACR.

Breast cancer screening in 21 countries: delivery of services, notification of results and outcomes ascertainment.

Following clinical trial evidence of mammography screenings efficacy and effectiveness, data are needed from organized population-based programmes to determine whether screening in these programmes results in breast cancer mortality reductions comparable to those demonstrated in controlled settings. The International Breast Cancer Screening Network (IBSN) conducted two international programme assessments: in 1990 among nine countries and in 1995 among 22 countries, obtaining information on the organization and process for screening within breast cancer screening programmes. This manuscript describes procedures for recruitment, service delivery, interpretation and communication of results, case ascertainment, and quality assurance. Practices in more established programmes are compared with pilot programmes. Each IBSN country defined a unique programme of population-based breast cancer screening. Some programmes were sub-national rather than national in scope, while others were in pilot stages of development. Screening took place in dedicated centres in established programmes and in both dedicated and general radiology centres in pilot programmes. Although most countries used personal invitation systems to recruit women to screening, other recruitment mechanisms were used. Most countries used two-view mammography in their screening programmes. About half had implemented independent double reading of mammograms, considering it a key component of high-quality mammography screening. In conclusion, diversity exists in the organization and delivery of screening mammography internationally. Quality assurance activities are a priority and are being evaluated in the IBSN.

Breast cancer in Swedish women before age 50: evidence of a dual effect of completed pregnancy

We set out to detect a transient increase in risk of breast cancer following childbirth, the existence of which has been postulated, but for which empirical evidence is contradictory. Breast cancers and births occurring among the cohort of Swedish women born after 1939 were linked, yielding 3,439 cases and 25,140 age-matched controls with at least two children. Within three years of their last childbirth, women had an estimated rate of breast cancer of 1.21 (95 percent confidence interval [CI]=1.02–1.44) times that of women whose last birth was 10 or more years earlier, after adjustment for parity and age at first birth. Further analyses suggested that this effect reflected, in part, a small transient increase in breast cancer risk that lasts for about three years following completed pregnancy. The effect of age at first birth on breast cancer risk appears to be confounded by time since last birth; the parity-adjusted rate ratio for having a first birth at age 35 years or more compared with under 20 years is reduced from 1.72 (CI=1.14–2.58) to 1.36 (CI=0.88–2.09) on additional adjustment for time since last birth. A transient increase in breast cancer risk after childbirth thus appears to account for part of the effect of age at first birth on breast cancer risk.

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.