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Background: The aim of this study was to quantify the impact of organised mammography screening on breast cancer mortality across European regions. Therefore, a systematic review was performed including different types of studies from all European regions and stringently used clearly defined quality appraisal to summarise the best evidence., Methods: Six databases were searched including Embase, Medline and Web of Science from inception to March 2018. To identify all eligible studies which assessed the effect of organised screening on breast cancer mortality, two reviewers independently applied predefined inclusion and exclusion criteria. Original studies in English with a minimum follow-up of five years that were randomised controlled trials (RCTs) or observational studies were included. The Cochrane risk of bias instrument and the Newcastle-Ottawa Scale were used to assess the risk of bias., Results: Of the 5015 references initially retrieved, 60 were included in the final analysis. Those comprised 36 cohort studies, 17 case-control studies and 7 RCTs. None were from Eastern Europe. The quality of the included studies varied: Nineteen of these studies were of very good or good quality. Of those, the reduction in breast cancer mortality in attenders versus non-attenders ranged between 33% and 43% (Northern Europe), 43%-45% (Southern Europe) and 12%-58% (Western Europe). The estimates ranged between 4% and 31% in invited versus non-invited., Conclusion: This systematic review provides evidence that organised screening reduces breast cancer mortality in all European regions where screening was implemented and monitored, while quantification is still lacking for Eastern Europe. The wide range of estimates indicates large differences in the evaluation designs between studies, rather than in the effectiveness of screening., Competing Interests: Conflict of interest statement The authors have declared no conflicts of interest., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: In Denmark, national roll-out of a population-based, screening mammography program took place in 2007-2010. We report on outcome of the first four biennial invitation rounds., Methods: Data on screening outcome were retrieved from the 2015 and 2016 national screening quality reports. We calculated coverage by examination; participation after invitation; detection-, interval cancer- and false-positive rates; cancer characteristics; sensitivity and specificity, for Denmark and for the five regions., Results: At the national level coverage by examination remained at 75-77%; lower in the Capital Region than in the rest of Denmrk. Detection rate was slightly below 1% at first screen, 0.6% at subsequent screens, and one region had some fluctuation over time. Ductal carcinoma in situ (DCIS) constituted 13-14% of screen-detected cancers. In subsequent rounds, 80% of screen-detected invasive cancers were node negative and 40% ≤10 mm. False-positive rate was around 2%; higher for North Denmark Region than for the rest of Denmark. Three out of 10 breast cancers in screened women were diagnosed as interval cancers., Conclusions: High coverage by examination and low interval cancer rate are required for screening to decrease breast cancer mortality. Two pioneer local screening programs starting in the 1990s were followed by a decrease in breast cancer mortality of 22-25%. Coverage by examination and interval cancer rate of the national program were on the favorable side of values from the pioneer programs. It appears that the implementation of a national screening program in Denmark has been successful, though regional variations need further evaluation to assure optimization of the program.

Background: Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening., Objective: To determine the association between receipt of screening mammography or PSA and overall survival., Design: Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001-2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening., Participants: A 5 % sample of Medicare beneficiaries aged 69-90 years as of 1/1/2003 (n = 906,723)., Interventions: Receipt of screening mammography in 2001-2002 for women, or a screening PSA test in 2002 for men., Main Measures: Survival from 1/1/2003 through 12/31/2012., Key Results: Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR = 1.52; 95 % CI = 1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR = 1.23; 1.22, 1.25)., Conclusions: Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy., Competing Interests: Compliance with Ethical Standards Funders This work was supported by grants from the National Institutes of Health (P30-AG024832, UL1TR000071 and KO5 CA 134923), the Agency for Healthcare Research and Quality (R24HS022134), and the Cancer Prevention Research Institute of Texas (RP101207). The sponsors played no role in the acquisition, analysis, or interpretation of data, or in determining where to send the manuscript for publication. Prior Presentations None. Conflict of Interest The authors declare that they do not have a conflict of interest.

The degree to which observed reductions in breast cancer mortality is attributable to screening mammography has become increasingly controversial. We examined this issue with three fundamentally different approaches: (i) Chronology--the temporal relationship of the onset of breast cancer mortality decline and the national implementation of screening mammography; (ii) Magnitude--the degree to which breast cancer mortality declined relative to the amount (penetration) of screening mammography; (iii) Analogy--the pattern of mortality rate reductions of other cancers for which population screening is not conducted. Chronology and magnitude were assessed with data from Europe and North America, with three methods applied to magnitude. A comparison of eight countries in Europe and North America does not demonstrate a correlation between the penetration of national screening and either the chronology or magnitude of national breast cancer mortality reduction. In the United States, the magnitude of the mortality decline is greater in the unscreened, younger women than in the screened population and regional variation in the rate of breast cancer mortality reduction is not correlated with screening penetrance, either as self-reported or by the magnitude of screening-induced increase in early-stage disease. Analogy analysis of United States data identifies 14 other cancers with a similar distinct onset of mortality reduction for which screening is not performed. These five lines of evidence from three different approaches and additional observations discussed do not support the hypothesis that mammography screening is a primary reason for the breast cancer mortality reduction in Europe and North America., (© 2015 UICC.)

In this paper, we study breast cancer screening policies using computer simulation. We developed a multi-state Markov model for breast cancer progression, considering both the screening and treatment stages of breast cancer. The parameters of our model were estimated through data from the Canadian National Breast Cancer Screening Study as well as data in the relevant literature. Using computer simulation, we evaluated various screening policies to study the impact of mammography screening for age-based subpopulations in Canada. We also performed sensitivity analysis to examine the impact of certain parameters on number of deaths and total costs. The analysis comparing screening policies reveals that a policy in which women belonging to the 40-49 age group are not screened, whereas those belonging to the 50-59 and 60-69 age groups are screened once every 5 years, outperforms others with respect to cost per life saved. Our analysis also indicates that increasing the screening frequencies for the 50-59 and 60-69 age groups decrease mortality, and that the average number of deaths generally decreases with an increase in screening frequency. We found that screening annually for all age groups is associated with the highest costs per life saved. Our analysis thus reveals that cost per life saved increases with an increase in screening frequency., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Denmark and Norway are the best countries to study effects of mammography screening, because they are the only countries with stepwise introduction of nationwide mammography screening, enabling comparative effectiveness studies of high quality. Although Denmark and Norway are countries with similar populations and health care systems, reported reductions in breast cancer mortality (incidence-based) caused by screening differed vastly; 25% in Denmark versus 10% in Norway. This study explores reasons for this difference., Patients and Methods: We compared two published studies from the Danish and Norwegian screening programs (Olsen et al., 2005; Kalager et al., 2010) investigating biennial mammography screening for women age 50-69 years. Four comparison groups of women were constructed ('current' and 'historical screening groups'; 'current' and 'historical nonscreening groups') based on county of residence. We calculated incidence-based breast cancer mortality in the current versus the historical period for screening and nonscreening groups, using mortality rate ratios (MRR) in the two countries, accounting for concomitant changes in breast cancer mortality., Results: In the screening groups, similar reductions in breast cancer mortality were found when periods preceding and following start of screening were compared, in Denmark [25%; MRR 0.75; 95% confidence interval (CI) 0.64% to 0.88%] and in Norway (28%; MRR 0.72; 95% CI 0.63% to 0.81%). However, mortality increased in Denmark in the current nonscreening group compared with the historical nonscreening group; for women >59 years, breast cancer mortality increased by 14% (MRR 1.14, 95% CI 1.07-1.22), whereas in Norway a 19% reduction was seen (MRR 0.81, 95% CI 0.72-0.92). This increase accounts for the different relative effect of screening in Denmark and Norway; 25% breast cancer mortality reduction in Denmark, 10% in Norway., Conclusions: The seemingly larger effect of screening in Denmark may not be solely attributable to screening itself, but to increased breast cancer mortality in women older than 59 years not invited to screening., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@ oup.com.)

Background: The objective of our meta-analysis and systematic review was to analyze non-breast cancer mortality in women screened with mammography versus non-screened women to determine whether there is excess mortality caused by screening., Methods: We searched PubMed and the Web of Science up to 30 November 2010. We included randomized controlled trials with non-breast cancer mortality as the main endpoint. Two authors independently assessed trial quality and extracted data., Results: There was no significant difference between groups at 13-year follow-up (odds ratio = 1.00 (95% CI 0.98 to 1.03) with average heterogeneity I2 = 61%) regardless of the age and the methodological quality of the included studies. The meta-analysis did not reveal excess non-breast cancer mortality caused by screening. If screening does have an effect on excess mortality, it is possible to provide an estimate of its maximum value through the upper confidence interval in good-quality methodological studies: up to 3% in the screened women group (12 deaths per 100,000 women)., Conclusions: The all-cause death rate was not significantly reduced by screening when compared to the rate observed in unscreened women. However, mammography screening does not seem to induce excess mortality. These findings improve information given to patients. Finding more comprehensive data is now going to be difficult given the complexity of the studies. Individual modeling should be used because the studies fail to include all the aspects of a complex situation. The risk/benefit analysis of screening needs to be regularly and independently reassessed.

Objective: Optimal US screening strategies remain controversial. We use six simulation models to evaluate screening outcomes under varying strategies., Methods: The models incorporate common data on incidence, mammography characteristics, and treatment effects. We evaluate varying initiation and cessation ages applied annually or biennially and calculate mammograms, mortality reduction (vs. no screening), false-positives, unnecessary biopsies and over-diagnosis., Results: The lifetime risk of breast cancer death starting at age 40 is 3% and is reduced by screening. Screening biennially maintains 81% (range 67% to 99%) of annual screening benefits with fewer false-positives. Biennial screening from 50-74 reduces the probability of breast cancer death from 3% to 2.3%. Screening annually from 40 to 84 only lowers mortality an additional one-half of one percent to 1.8% but requires substantially more mammograms and yields more false-positives and over-diagnosed cases., Conclusion: Decisions about screening strategy depend on preferences for benefits vs. potential harms and resource considerations., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: To compare trends in breast cancer mortality within three pairs of neighbouring European countries in relation to implementation of screening., Design: Retrospective trend analysis., Setting: Three country pairs (Northern Ireland (United Kingdom) v Republic of Ireland, the Netherlands v Belgium and Flanders (Belgian region south of the Netherlands), and Sweden v Norway)., Data Sources: WHO mortality database on cause of death and data sources on mammography screening, cancer treatment, and risk factors for breast cancer mortality., Main Outcome Measures: Changes in breast cancer mortality calculated from linear regressions of log transformed, age adjusted death rates. Joinpoint analysis was used to identify the year when trends in mortality for all ages began to change., Results: From 1989 to 2006, deaths from breast cancer decreased by 29% in Northern Ireland and by 26% in the Republic of Ireland; by 25% in the Netherlands and by 20% in Belgium and 25% in Flanders; and by 16% in Sweden and by 24% in Norway. The time trend and year of downward inflexion were similar between Northern Ireland and the Republic of Ireland and between the Netherlands and Flanders. In Sweden, mortality rates have steadily decreased since 1972, with no downward inflexion until 2006. Countries of each pair had similar healthcare services and prevalence of risk factors for breast cancer mortality but differing implementation of mammography screening, with a gap of about 10-15 years., Conclusions: The contrast between the time differences in implementation of mammography screening and the similarity in reductions in mortality between the country pairs suggest that screening did not play a direct part in the reductions in breast cancer mortality.

Comparison of breast cancer mortality between pairs of similar countries (Sweden and Norway, Northern Ireland and the Irish Republic, the Netherlands and Belgium or Flanders), each of which had implemented its population-wide breast cancer screening programme at a different point in time, demonstrated little effect of screening on mortality. In the Netherlands, a well-organised population-wide screening programme was started in the early nineties, ten years before such a programme was introduced in Flanders. We used the 1989-1992 period as a baseline and compared breast cancer mortality in the Netherlands with that in Flanders during the 2005-2008 period. The added value of organised screening was low: 11% in the target age group of 55-79 years, or 180 prevented breast-cancer deaths annually. A total of 5000 screening mammograms were needed to prevent one death from breast cancer. Breast cancer screening is not a public health priority. Impartial and transparent information on the disadvantages and benefits of breast cancer screening is urgently needed.

Objective: To determine whether the previously observed 25% reduction in breast cancer mortality in Copenhagen following the introduction of mammography screening was indeed due to screening, by using an additional screening region and five years additional follow-up., Design: We used Poisson regression analyses adjusted for changes in age distribution to compare the annual percentage change in breast cancer mortality in areas where screening was used with the change in areas where it was not used during 10 years before screening was introduced and for 10 years after screening was in practice (starting five years after introduction of screening)., Setting: Copenhagen, where mammography screening started in 1991, and Funen county, where screening was introduced in 1993. The rest of Denmark (about 80% of the population) served as an unscreened control group., Participants: All Danish women recorded in the Cause of Death Register and Statistics Denmark for 1971-2006., Main Outcome Measure: Annual percentage change in breast cancer mortality in regions offering mammography screening and those not offering screening., Results: In women who could benefit from screening (ages 55-74 years), we found a mortality decline of 1% per year in the screening areas (relative risk (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.01) during the 10 year period when screening could have had an effect (1997-2006). In women of the same age in the non-screening areas, there was a decline of 2% in mortality per year (RR 0.98, 95% CI 0.97 to 0.99) in the same 10 year period. In women who were too young to benefit from screening (ages 35-55 years), breast cancer mortality during 1997-2006 declined 5% per year (RR 0.95, CI 0.92 to 0.98) in the screened areas and 6% per year (RR 0.94, CI 0.92 to 0.95) in the non-screened areas. For the older age groups (75-84 years), there was little change in breast cancer mortality over time in both screened and non-screened areas. Trends were less clear during the 10 year period before screening was introduced, with a possible increase in mortality in women aged less than 75 years in the non-screened regions., Conclusions: We were unable to find an effect of the Danish screening programme on breast cancer mortality. The reductions in breast cancer mortality we observed in screening regions were similar or less than those in non-screened areas and in age groups too young to benefit from screening, and are more likely explained by changes in risk factors and improved treatment than by screening mammography.

The Valencian Breast Cancer Early Detection Program (VBCEDP) started in the Valencian Community (Spain) in 1992. Up to now, 24 mammographic units have been installed all over the region. Mammography is used to aid in the diagnosis of breast cancer diseases in women. There is a health risk in the studied women due to ionising radiation that has to be estimated and controlled. A methodology to calculate approximately the radiological detriment in the VBCEDP has been developed based on Monte Carlo techniques. It has been used, as qualitative parameter, the average mean glandular dose from representative sample populations undergoing screening mammography (digital or screenfilm) from each of the twenty-four units in operation. The American College of Radiology Imaging Network reached to conclusion that digital mammography performed significantly better than film for pre and perimenopausal women younger than 50. Women who are undergoing the program are between 45 and 69. This fact allows us to study premenopausic women. Our group uses the software SCREENRISK to estimate induction and mortality rates in order to corroborate American conclusions in an European region. The obtained results confirm the American results about the application of digital mammography in pre and perimenopausal women younger than 50 years.

12,987 invasive breast cancer cases were diagnosed in women aged 50-69 upto the year 2001 in nine Italian areas where a screening programme was active. Cases were followed up in 2005 for a total of 1921 breast cancer failures. The 10-year survival rates were 85.3% for the invited group against 75.6% for the non-invited. A time dependent analysis was performed using 5-year intervals. Crude hazard ratios for the invited group in comparison to the not invited group were 0.52 and 0.64 respectively in the (0-5) year and [5-10] year time windows. Hazard ratio adjusted for tumour characteristics was 0.96 in the [5-10] year time window, suggesting minimal or any length bias. Consistent with the results of randomised trials, these analyses of service screening data document a mortality reduction of 36% at 5-10 years after diagnosis.

Comparisons of cancer mortality between users and nonusers of screening are potentially biased because of the effects of self-selection. Previous studies of breast screening have found that individuals likely to participate have lower breast cancer mortality than those unlikely to participate. This study compares the incidence, survival and mortality for all cancer types other than breast between participants and nonparticipants in a service screening mammography program. British Columbian females having their first mammogram between the ages of 40 and 79 and the years 1988 and 2004 were identified as a cohort of "participants". Person-years of follow-up of participants were aggregated by age and year. Nonparticipant person-years were obtained by subtraction from the total female population. Cancer diagnoses other than breast were identified for participants and nonparticipants. Age, calendar year, and income adjusted relative risks of cancer incidence were estimated from generalized additive models with Poisson errors. Hazard ratios were estimated by Cox regression. Observed cancer mortality in participants was compared with expected mortality generated from nonparticipant incidence and survival rates. Incidence rates of cancer showed a mixed relationship with some elevated, some decreased and others similar to nonparticipant rates. Cancer survival was higher among participants for most cancer types, with an overall hazard ratio of 0.76 (0.73-0.79). Observed mortality in participants was less than expected for most cancers, with an overall mortality ratio of 0.60 (0.58-0.62). The general cancer experience of screening program participants is different from that of the general population., (Copyright 2007 Wiley-Liss, Inc.)

The 5-year relative survival from breast cancer in Denmark is 10 percentage points lower than in Sweden. This difference has been demonstrated previously as being caused partly by more involved lymph nodes and larger tumours in Denmark. Sweden has had nationwide mammography-screening coverage since 1991, whereas this is still in its infancy in Denmark. In the search for an explanation for the remaining survival difference, patient delay was a likely candidate. This study compared patient delay and mammography-detection between two national regions. Data on patient delay and mammography were obtained from hospital records from 1989 and 1994, and analysed using Cox proportional hazard analysis of death within the first 5 years, with the factors age, country, delay/mammography detection and established patho-anatomic variables. A comparison of patient delay and mammography detection in 1989 and 1994 showed more mammography-detected tumours in south Sweden and more women with long delay in east Denmark. Mammography detection, but not long patient delay, had a significant effect on the death hazard when adjusting for patho-anatomic risk factors. The hazard ratio was not eliminated in 1989, but in 1994, the hazard ratio between east Denmark and south Sweden was reduced from 1.3 to 1.1. In conclusion, patient delay did not appear to have any effect on 5-year survival when adjusting for patho-anatomic factors, but tumour detection by mammography affected survival favourably and partly explained the survival difference between east Denmark and south Sweden.

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 rates fell between 1990 and 2000. When something positive occurs in medicine attempts are usually made to explain the observation or claim the credit. In this case, credit has been given to improvements in standard treatments and to increased use of mammography, each said to have made a contribution. Published data on the results of clinical trials utilising high-dose radiation or chemotherapy do not support this position. Improvements in breast cancer mortality are more likely to be the result of the biopositive effects of the low-dose radiation delivered during mammography, based on lower death rates from breast cancer in women subjected to repetitive mammographic screening, albeit with no significant change in all-cause death rates. This is supported by a study in which breast cancer rates were lowered by diagnostic X-rays of the chest.

Between 1976 and 1982, four randomized mammography screening trials started in five screening centres in Sweden, involving 282,777 women (156,911 invited and 125,866 controls) with the aim to study if invitation to screening reduced the breast cancer mortality. An overview of the trials was performed to reduce the confidence intervals for the relative risk estimates. All 1,296 deaths occurring in women with breast cancer detected after randomization were evaluated by an independent endpoint committee (EPC), consisting of four physicians who reviewed collected medical information that was blinded regarding mammography screening. If there was disagreement between the EPC members at the initial individual evaluation the final classification was made at consensus meetings. In only 6.9% (n = 89) of the cases was there disagreement as to whether breast cancer was or was not the underlying cause of death. It was also found that 'breast cancer as underlying cause of death' and 'breast cancer as underlying or contributory cause of death' according to Statistics Sweden resulted in relative risk estimates very similar to those based on the classification by the EPC. The study thus supports the use of official health statistics in the evaluation of randomized breast screening trials in Sweden.