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Objective: To analyze differences between screen-detected and non-screen-detected invasive breast cancers by tumour characteristics and age at diagnosis in the nationwide population-based mammography screening program in Sweden., Methods: Data were retrieved from the National Quality Register for Breast Cancer for 2008-2017. Logistic regression analysis was used to estimate the likelihood for a tumour to be screen-detected by tumour characteristics and age group at diagnosis., Results: In total there were 51,429 invasive breast cancers in the target age group for mammography screening of 40-74 years. Likelihood of screen detection decreased with larger tumour size, lymph node metastases, higher histological grade and distant metastasis. Odds ratios (ORs) for negative oestrogen (ER) and progesterone (PgR) were 0.41 and 0.57; for positive HER2, 0.62; for Ki-67 high versus low, 0.49. Molecular sub-types had OR of 0.56, 0.40 and 0.28, respectively, for luminal B-like, HER2-positive and triple negative versus luminal A-like. Adjusting for tumour size (T), lymph node status (N), age, year and county at diagnosis slightly elevated the ORs. Statistically significant interactions between tumour characteristics and age were found ( p  < 0.05) except for ER and PgR. The age group 40-49 deviated most from the other age groups., Conclusions: Our study demonstrates that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected after adjusting for age, year and county of diagnosis, and even after adjusting for T and N. The trend towards favourable tumour characteristics was less pronounced in the 40-49 age group compared to the other age groups, except for ER and PgR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Adjuvant endocrine treatment (AET) is crucial in early oestrogen receptor (ER)-positive breast cancer (BC), providing reduced recurrence rate and increased overall survival. The aim of this study was to estimate AET adherence rates by age at diagnosis and region in Sweden., Patients and Methods: In total, 10,422 women diagnosed with ER-positive BC in 2008-2010 were identified in the Swedish National BC Registry. Information on prescriptions and dispensation of AET was gathered through record linkage to the Swedish Prescription Registry. 1, 3- and 5-year medication possession ratios (MPRs) were calculated. Good adherence was set as MPR ≥ 80%., Results: The 1-, 3- and 5-year AET age-adjusted adherence rates were 94.4, 87.6 and 81.6%, respectively. The 1-, 3- and 5- year adherence rate was significantly highest in the South region (96.2, 90.5 and 86.2%). Regions with an oncologic clinic had higher adherence rate than regions without, 82.8% versus 75.5% at 5-year FU. Women at age 40-64 years (95.6, 89.9 and 84.1%) and 65-74 years at diagnosis (95.7, 89.5 and 84.6%) had significantly higher adherence rate than women ≥ 75 years at diagnosis (89.1, 79.2 and 68.3%)., Interpretations: Despite guidelines being national, there were significant differences in adherence between regions in Sweden. As the largest differences were between age groups invited and not invited to mammography screening intervention should focus on women < 40 and ≥ 75 years at diagnosis. Further studies are needed to find strategies to increase overall adherence to AET in early BC.

Background and Purpose: We have recently demonstrated that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected. The objective of the study was to analyse differences in breast cancer treatment between screen-detected and non-screen-detected cases by age at diagnosis, with and without adjustment for tumour (T) and nodal (N) status, within a nationwide, population-based mammography screening programme utilising register data., Material and Methods: Data spanning 2008-2017 were collected from the National Quality Register for Breast Cancer. Multivariable logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for treatment disparities between screen-detected and non-screen-detected breast cancer., Results: Among 46,481 women diagnosed with invasive breast cancer aged 40-74 and invited for mammography screening, significant differences in treatment were observed. Screen-detected cases showed higher likelihoods of partial mastectomy compared to mastectomy, endocrine therapy, and radiotherapy, whereas chemotherapy and antibody therapy were less likely compared to non-screen-detected cases. However, when adjusting for surgery type, screen-detected cases showed lower likelihoods of radiotherapy. Age at diagnosis significantly influenced treatment odds ratios, with interactions observed for all treatments except radiotherapy adjusted for surgery. Differences increased with age, except for endocrine therapy. Radiotherapy adjusted for surgery type showed no age-related interaction. Adjusting for T and N did not alter these patterns., Interpretation: In general, screen-detected cases received less aggressive treatment, such as mastectomy, chemotherapy, and antibody therapy, compared to non-screen-detected cases. Disparities increased with age, except for endocrine therapy and radiotherapy adjusted for surgery. Differences persisted after adjusting for T and N, suggesting that these factors cannot solely explain the results.

Objectives: To estimate the impact on the effectiveness of Swedish breast cancer screening program in women aged 40-49 years of shortening the screening interval from 21 months to 18 or 12 months., Methods: The reduction in breast cancer mortality among participants in screening with mammography was previously estimated in the Swedish SCReening of Young women (SCRY) study to be 29%. The expected increased effectiveness with a hypothetical shorter screening interval than the average of 21 months in SCRY was calculated using data about the women who died from breast cancer even though they participated in the SCRY program., Results: During the study period, 547 women who participated in the index screening round died from breast cancer. Shortening the screening interval to 18 months led to an improved effectiveness of 0.7-3.9% considering interval cancers only and of 1.3-7.6% considering screening-detected cancers only, and for both interval and screening-detected cancers the improvement was 1.9-11.5% when the assumed mortality reduction for the deceased cases varied from 5% to 30%. Shortening the screening interval to 12 months increased the effectiveness by 1.6-9.8% for interval cancers and by 2.9-17.4% for both interval and screening-detected cancers., Conclusion: Shortening the screening interval for women aged 40-49 years to 18 or 12 months might further reduce the breast cancer mortality rate.

Background: Consensus has been reached on the effectiveness of inviting women aged 50 to 69 years to mammography screening, but for older women, the evidence is scarce. The aim of this study was to estimate the marginal effectiveness of inviting women to mammography screening with an upper age limit of 74 years versus stopping at age 69 using data from the Swedish service-screening program., Methods: A cohort design was used to compare the breast cancer mortality in the period 1986 to 2012 between geographic areas and periods where women were invited to screening up to the age of 74 years (study group) with those where women were invited up to age 69 (control group). The study group and the control group were compared using the incidence-based breast cancer mortality rate ratio where only breast cancer deaths in cases diagnosed at 70 to 74 years of age were counted., Results: After 20 years of follow-up, there were 1,040 and 1,173 breast cancer deaths in the study and the control group, respectively. The breast cancer mortality rate ratio for women invited up to age 74 versus women invited up to age 69 was 0.80 [95% confidence interval (CI): 0.75-0.85] after bias adjustments. The corresponding rate ratio for participating women was 0.73 (95% CI: 0.66-0.81)., Conclusions: Continuing to screen women up to 74 years of age is effective compared with stopping screening at 69 years., Impact: This large long-term study will add to the knowledge of the effect of mammography screening for women 70 to 74 years., (©2020 American Association for Cancer Research.)

Background: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection., Methods: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries., Results: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate., Conclusion: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers., Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence., Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.

Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission (EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.

Background: Overdiagnosis, defined as the detection of a cancer that would not become clinically apparent in a woman's lifetime without screening, has become a growing concern. Similar underlying risk of breast cancer in the screened and control groups is a prerequisite for unbiased estimates of overdiagnosis, but a contemporary control group is usually not available in organized screening programs., Methods: We estimated the frequency of overdiagnosis of breast cancer due to screening in women 50-69 years old by using individual screening data from the population-based organized screening program in Stockholm County 1989-2014. A hidden Markov model with four latent states and three observed states was constructed to estimate the natural progression of breast cancer and the test sensitivity. Piecewise transition rates were used to consider the time-varying transition rates. The expected number of detected non-progressive breast cancer cases was calculated., Results: During the study period, 2,333,153 invitations were sent out; on average, the participation rate in the screening program was 72.7% and the average recall rate was 2.48%. In total, 14,648 invasive breast cancer cases were diagnosed; among the 8305 screen-detected cases, the expected number of non-progressive breast cancer cases was 35.9, which is equivalent to 0.43% (95% confidence interval (CI) 0.10%-2.2%) overdiagnosis. The corresponding estimates for the prevalent and subsequent rounds were 15.6 (0.87%, 95% CI 0.20%-4.3%) and 20.3 (0.31%, 95% CI 0.07%-1.6%), respectively. The likelihood ratio test showed that the non-homogeneous model fitted the data better than an age-homogeneous model (P <0.001)., Conclusions: Our findings suggest that overdiagnosis in the organized biennial mammographic screening for women 50-69 in Stockholm County is a minor phenomenon. The frequency of overdiagnosis in the prevalent screening round was higher than that in subsequent rounds. The non-homogeneous model performed better than the simpler, traditional homogeneous model.

Objectives: Overdiagnosis is regarded as a harm of screening. We aimed to develop a non-homogeneous multi-state model to consider the age-specific transition rates for estimation of overdiagnosis, to validate the model by a simulation study where the true frequency of overdiagnosis can be calculated, and to compare our estimate with the cumulative incidence method., Methods: We constructed a four-state model to describe the natural history of breast cancer. The latent disease progression and the observed states for each individual were simulated in a trial with biennial screening of women aged 51-69 and a control group of the same size without screening. We performed 100 repetitions of the simulation with one million women to evaluate the performance of estimates. A sensitivity analysis with reduced number of controls was performed to imitate the data from the service screening programme., Results: Based on the 100 repetitions, the mean value of the true frequency of overdiagnosis was 12.5% and the average estimates by the cumulative incidence method and the multi-state model were 12.9% (interquartile range: 2.46%) and 13.4% (interquartile range: 2.16%), respectively. The multi-state model had a greater bias of overdiagnosis than the cumulative incidence method, but the variation in the estimates was smaller. When the number of unscreened group was reduced, the variation of multi-state model estimates increased., Conclusions: The multi-state model produces a proper estimate of overdiagnosis and the results are comparable with the cumulative incidence method. The multi-state model can be used in the estimation of overdiagnosis, and might be useful for the ongoing service screening programmes.

Objective To analyze the age- and trial-specific effects of the breast cancer screening trials with mammography in Malmö, Stockholm, and Göteborg. Methods The original trial files were linked to the Swedish Cancer and Cause of Death Registers to obtain date of breast cancer diagnosis and date and cause of death. Relative risks and 95% confidence intervals were calculated using the evaluation model (only breast cancers diagnosed between date of randomization and date when the first screening round of the control group was completed were included in the analysis). Results Women aged 40-70 at randomization in the Malmö I and II, Stockholm, and Göteborg trials were followed-up for an average of 30, 22, 25, and 24 years, respectively. The overview of all trials resulted in a significant decrease of 15% in breast cancer mortality. The variation by consecutive 10-year age group at randomization was small-from 21% in the age group 40-49 to 11% in the age group 50-59. After adjustment for age, there was a significant reduction in breast cancer mortality in the Göteborg trial (26%), and a non-significant reduction in the Malmö I and II and Stockholm trials (12%, 15%, and 5.8%, respectively). Conclusions The overview showed a 15% significant relative reduction in breast cancer mortality due to invitation to mammography screening. Heterogeneity in age, trial time, attendance rates, and length of screening intervals may have contributed to the variation in effect between the trials.

Background: Invitation to mammography screening of women aged 40 to 49 years is a matter of debate in many countries and a cost-effective alternative in countries without screening among women aged 40 to 49 years could be inviting those at higher risk. The relative effectiveness of mammography screening was estimated for subgroups based on the breast cancer risk factors parity, age at time of birth of first child, and socioeconomic status (SES)., Methods: The SCReening of Young Women (SCRY) database consists of all women aged 40 to 49 years in Sweden between 1986 and 2005 and was split into a study and control group. The study group consisted of women residing in areas in which women aged 40 to 49 years were invited to screening and the control group of women in areas in which women aged 40 to 49 years were not invited to screening. Rate ratio (RR) estimates were calculated for 2 exposures: invitation and attendance., Results: There were striking similarities noted in the RR pattern for women invited to and attending screening and no statistically significant difference or trend in the RR was noted by risk group. The RR estimates increased by increasing parity for parity of 0 to 2 and ranged from 0.55 (95% confidence interval [95% CI], 0.38-0.79) to 0.79 (95% CI, 0.65-0.95) for attending women. The RR for women with high SES was lower than that for women with low SES (RR, 0.72 [95% CI, 0.60-0.86] and RR, 0.79 [95% CI, 0.63-0.99], respectively). For women aged 20 to 24 years at the time of the birth of their first child, the RR was 0.73 (95% CI, 0.58-0.91) and estimates for other ages were similar., Conclusions: There was no statistically significant difference noted in the relative effectiveness of mammography screening by parity, age at the time of birth of the first child, or SES., (© 2014 American Cancer Society.)

Background: Breast cancer is the most common cancer afflicting women in Jordan. This study aimed to assess the effects of an educational intervention through home visits, including offering free mammography screening vouchers, on changing women's breast health knowledge and screening practices for early detection of breast cancer in a less privileged area in Jordan., Methods: Two thousand four hundred breast health awareness home visits were conducted and 2363 women aged 20-79 years (median: 41) answered a pre-test interview-administrated questionnaire to assess their breast health knowledge and practices at the baseline. After a home-based educational session, 625 women aged 40 years or older were referred to free mammography screening. Five hundred and ninety six homes were revisited six months later and out of these 593 women participated in a post-test. The women's retained breast health knowledge, the changes in their reported breast health practices and their usage of the free mammography voucher, were assessed., Results: The mean knowledge score increased significantly (p < 0.001) from 11.4 in the pre-test to 15.7 in the post-test (maximum score: 16). At the six month follow-up the post-test showed significant (p < 0.001) improvement in women's perceived breast self-examination (BSE) knowledge, reported BSE practice and mammography screening. Out of 625 women that received a voucher for free mammography screening 73% attended the mammography unit, while only two women without a voucher went for mammography screening at the assigned unit. Women who received a follow-up visit were more likely to use the free mammography voucher compared to those who were not followed-up (83% vs. 67%; p < 0.001)., Conclusions: Home visits by local community outreach workers that incorporated education about breast cancer and breast health in addition to offering free mammography screening vouchers were effective in improving women's breast health knowledge and practices in a less privileged area in Jordan.

Background: Breast cancer is the most common malignancy afflicting women, and the most common cancer overall in Jordan. A woman's decision to go for screening is influenced by her social support network. This study aims to explore Jordanian men's individual and contextual perspectives on women's breast cancer and their own role in the breast health of the females within their families., Methods: An explorative qualitative design was used to purposively recruit 24 married men aged 27 to 65 years (median 43 years) from four governorates in Jordan. Data in the form of interviews transcriptions was subjected to qualitative content analysis., Results: Three themes were identified: a) Supporting one's wife; b) Marital needs and obligations; c) Constrained by a culture of destiny and shame. The first theme was built on men's feelings of responsibility for the family's health and well-being, their experiences of encouraging their wives to seek health care and their providing counselling and instrumental support. The second theme emerged from men's views about other men's rejection of a wife inflicted by breast cancer, their own perceptions of diminished femininity due to mastectomy and their own concerns about protecting the family from the hereditary risk of breast cancer. The third theme was seen in men's perception of breast cancer as an inevitable act of God that is far away from one's own family, in associating breast cancer with improper behaviour and in their readiness to face the culture of Eib (shame)., Conclusions: Jordanian men perceive themselves as having a vital role in supporting, guiding and encouraging their wives to follow breast cancer early detection recommendations. Breast health awareness campaigns could involve husbands to capitalize on family support.

Background: Breast cancer is the leading cause of cancer mortality among Jordanian women. Breast malignancies are detected at late stages as a result of deferred breast health-seeking behaviour. The aim of this study was to explore Jordanian women's views and perceptions about breast cancer and breast health., Methods: We performed an explorative qualitative study with purposive sampling. Ten focus groups were conducted consisting of 64 women (aged 20 to 65 years) with no previous history and no symptoms of breast cancer from four governorates in Jordan. The transcribed data was analysed using latent content analysis., Results: Three themes were constructed from the group discussions: a) Ambivalence in prioritizing own health; b) Feeling fear of breast cancer; and c) Feeling safe from breast cancer. The first theme was seen in women's prioritizing children and family needs and in their experiencing family and social support towards seeking breast health care. The second theme was building on women's perception of breast cancer as an incurable disease associated with suffering and death, their fear of the risk of diminished femininity, husband's rejection and social stigmatization, adding to their apprehensions about breast health examinations. The third theme emerged from the women's perceiving themselves as not being in the risk zone for breast cancer and in their accepting breast cancer as a test from God. In contrast, women also experienced comfort in acquiring breast health knowledge that soothed their fears and motivated them to seek early detection examinations., Conclusions: Women's ambivalence in prioritizing their own health and feelings of fear and safety could be better addressed by designing breast health interventions that emphasize the good prognosis for breast cancer when detected early, involve breast cancer survivors in breast health awareness campaigns and catalyse family support to encourage women to seek breast health care.

Objectives: To estimate the level of overdiagnosis of all breast cancers and of invasive breast cancers in women aged 40-49 invited to the subsequent screening rounds in the Swedish service-screening programme 1986-2005., Methods: To estimate the level of overdiagnosis in subsequent screening, the rate ratios (RR) of the breast cancer incidence in the study group (women in areas with screening in ages 40-49) and the control group (women in areas with no screening in ages 40-49) were calculated for all breast cancers and for invasive breast cancers. The RR estimates were adjusted for the prescreening difference in incidence between study and control group and for lead time., Results: The prescreening incidence rate ratio was estimated at 0.92 (95% confidence interval [CI]: 0.88-0.97). The number of breast cancer cases and person-years were 6047 and 3.8 million, and 7790 and 5.2 million, in the study group and control group respectively during the study period. The RR estimate for all cancers was 1.01 (95% CI: 0.94-1.08) when adjusted for prescreening difference and a lead time of 1.2 years. The corresponding estimate for invasive breast cancers was 0.95 (95% CI: 0.88-1.02)., Conclusions: We found no significant overdiagnosis for women aged 40-49 in the Swedish service screening programme with mammography.

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 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 summarize participation and coverage rates in population mammographic screening programmes for breast cancer in Europe., Methods: We used the European Network for Information on Cancer (EUNICE), a web-based data warehouse (EUNICE Breast Cancer Screening Monitoring, EBCSM) for breast cancer screening, to obtain information on programme characteristics, coverage and participation from its initial application in 10 national and 16 regional programmes in 18 European countries., Results: The total population targeted by the screening programme services covered in the report comprised 26.9 million women predominantly aged 50-69. Most of the collected data relates to 2005, 2006 and/or 2007. The average participation rate across all programmes was 53.4% (range 19.4-88.9% of personally invited); or 66.4% excluding Poland, a large programme that initiated personal invitations in 2007. Thirteen of the 26 programmes achieved the European Union benchmark of acceptable participation (>70%), nine achieved the desirable level (>75%). Despite considerable invitation coverage across all programmes (79.3%, range 50.9-115.2%) only 48.2% (range 28.4-92.1%) of the target population were actually screened. The overall invitation and examination coverage excluding Poland was 70.9% and 50.3%, respectively., Conclusions: The results demonstrate the feasibility of European-wide screening monitoring using the EBCSM data warehouse, although further efforts to refine the system and to harmonize standards and data collection practices will be required, to fully integrate all European countries. The more than three-fold difference in the examination coverage should be taken into account in the evaluation of service screening programmes.

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: 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.

Background: The effectiveness of mammography screening for women ages 40 to 49 years still is questioned, and few studies of the effectiveness of service screening for this age group have been conducted., Methods: Breast cancer mortality was compared between women who were invited to service screening at ages 40 to 49 years (study group) and women in the same age group who were not invited during 1986 to 2005 (control group). Together, these women comprise the Mammography Screening of Young Women (SCRY) cohort, which includes all Swedish counties. A prescreening period was defined to facilitate a comparison of mortality in the absence of screening. The outcome measure was refined mortality, ie, breast cancer death for women who were diagnosed during follow-up at ages 40 to 49 years. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated., Results: There was no significant difference in breast cancer mortality during the prescreening period. During the study period, there were 803 breast cancer deaths in the study group (7.3 million person-years) and 1238 breast cancer deaths in the control group (8.8 million person-years). The average follow-up was 16 years. The estimated RR for women who were invited to screening was 0.74 (95% CI, 0.66-0.83), and the RR for women who attended screening was 0.71 (95% CI, 0.62-0.80)., Conclusions: In this comprehensive study, mammography screening for women ages 40 to 49 years was efficient for reducing breast cancer mortality., (Copyright © 2010 American Cancer Society.)

Background: Breast cancer is the most common cancer among women in Jordan and on average 70% of the cases present at advanced stages. The aim of this study was to assess the effectiveness of a public educational campaign conducted by the Jordan Breast Cancer Program to improve breast health knowledge among Jordanian women and to relate their knowledge to breast health practices., Methods: The campaign was conducted in five governorates in Jordan with a total of 105 public group lectures about breast cancer focusing on early detection. The total number of participants was 2,554 women with a median age of 37 years (range: 15-73 years). Median number of women per lecture was 24 (range: 9-38). Before the lectures, the women answered a structured questionnaire about their knowledge and practices. After the intervention 2,418 of them filled a post-test questionnaire with the same content. Correct answers on the 15 knowledge questions yielded a maximum score of 15. Determinants of breast health practices were identified using multivariable logistic regression analysis., Results: The mean knowledge score increased significantly from 10.9 in the pre-test to 13.5 in the post-test (p<0.001). The percentage with a minimum of 14 correct answers to the 15 questions increased from 18 to 63% (p<0.001). Adequate breast health practices were generally low but increased significantly with increasing age and attendance at a previous lecture on breast cancer. Breast health practices were also higher among married women and housewives, and significantly associated with older age and greater breast health knowledge (p<0.001)., Conclusions: Group educational lectures appeared effective for improving breast health knowledge among Jordanian women. However, even with the noticeable level of knowledge at the baseline, there were low breast health practices among the study participants. This necessitates further in-depth research to explore womens experiences and socio-cultural barriers to breast health seeking behaviour in Jordan.

Objectives: To estimate the interval cancer incidence, its determinants and the episode sensitivity in the Norrbotten Mammography Screening Programme (NMSP)., Setting: Since 1989, women aged 40-74 years (n = 55,000) have been invited to biennial screening by the NMSP, Norrbotten county, Sweden., Methods: Data on 1047 invasive breast cancers from six screening rounds of the NMSP (1989-2002) were collected. We estimated the invasive interval cancer rates, rate ratios and the episode sensitivity using the detection and incidence methods. A linear Poisson-model was used to analyse association between interval cancer incidence and sensitivity., Results: 768 screen-detected and 279 interval cancer cases were identified. The rate ratio of interval cancer decreased with age. The 50-59 year age group showed the highest rate ratio (RR = 0.52, 95% CI 0.41-0.65) and the 70-74 year age group the lowest (RR = 0.23, 95% CI 0.15-0.36). The rate ratios for the early (0-12 months) and late (13-24 months) interval cancers were similar (RR = 0.18, 95% CI 0.15-0.22 and 0.20, 95% CI 0.17-0.24). There was a significantly lower interval cancer incidence in the prevalence round as compared with the incidence rounds. According to the detection method the episode sensitivity increased with age from 57% in the age group 40-49 years to 84% in the age group 70-74 years. The corresponding figures for the incidence method were 50% and 77%, respectively., Conclusion: Our study showed an interval cancer incidence of 38% and the episode sensitivity of 62-73%, depending on the method of calculation. Our results are of clinically acceptable level and concert with the reference values of the European guidelines.

Background: Both adjuvant therapy and mammography screening can decrease breast cancer mortality and there is a need of knowing to what extent those two modalities are used in the population. Screening coverage is well documented but there is a scarcity of population-based data on use of systemic adjuvant treatment., Aim: To describe the introduction, and trends in the use of adjuvant systemic therapy for breast cancer in two of six public health regions in Sweden., Material & Methods: Population-based data on use of adjuvant therapy were available from databases with documented high quality and high coverage data for Stockholm (1976-2005) and North Sweden (1980-2003, and 2005)., Results: The use of systemic treatment was infrequent before the late 1980s in both regions, but increased during the 1990s. In 2005, the proportion of operable breast cancer patients treated with adjuvant endocrine therapy in the ages 40-59 was around 60 to 80%. The proportion adjuvant chemotherapy was less than 15% for the ages 70-74. For the north region the use of endocrine therapy increased successively over time, with an exception for age group 40-49 were a more rapidly increase occurred in the late 1990s. In Stockholm the increment was higher and more rapidly. There was no clear difference in chemotherapy use between the regions, and the use increased from the mid 1980s in age group 40-49, and in the early 1990s for women aged 50-59. In age group's 60-69 and 70-74 the use was relatively infrequent., Conclusions: Trends in, and levels of the use of adjuvant systemic therapy for breast cancer varied over time in the two study regions, particularly for endocrine therapy. We consider that the differences between the regions mainly reflect different interpretations of new scientific evidence. We stress the importance of a good documentation of all new treatment protocols.

Objectives: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention., Setting: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination., Method: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths., Results: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest., Conclusions: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

In cancer screening, it is considered mandatory not only to prove the efficacy of the screening test, but also, as a permanent commitment, to demonstrate and quantify the effectiveness of service screening in terms of mortality reduction when the test becomes part of a screening programme. In Germany, a nationwide organized and quality-assured mammography screening programme among 50-69-year-old women, a target population of about 10 million women, is currently implemented. The envisaged short implementation period of about 2 years raises the issue of how to estimate the effectiveness of the programme in terms of long-term mortality reduction. On the basis of sample size calculations, a strategy for evaluation of mortality reduction is outlined. Our approach compares breast cancer mortality in different geographical areas or temporally within geographical areas. The latter design appears useful also for established programmes to examine site-specific mortality reduction by screening in late-starting areas, which are frequently used as control areas of a geographical comparison, but rarely a subject of evaluation on their own. Emphasis has to be put on the collection of the required data from the very beginning of the programme. For this, performance of cancer registration and proper linkage with the screening programme must be enhanced. In the trade-off between data protection and public interest in quality-assurance of medical care, emphasis should be put on assurance of high-level medical care whose relevance may be counted in terms of the numbers of deaths prevented. It is from this the individual truly benefits.

The aim of this study was to estimate breast cancer survival according to detection mode for 5120 women with invasive breast cancer, in particular for those detected in the screening intervals. We found a significant survival difference in favour of women with cancer detected in the screening intervals (n=729) compared with those uninvited (n=1879) during the 13-year follow-up. Detection mode was proven to modify the prognostic effect of stage. Women with stage I interval cancer had shorter survival and those with stage II had longer survival than expected. It is suggested that interval cancers might consist of two subgroups with different behaviour: one of fast-growing tumours presenting as stage I cases and another of slow-growing tumours presenting as stage II+ cases. A hypothesis related to this observation is discussed.

Objectives: To study the effectiveness of service screening with mammography in Northern Sweden., Setting: Two counties which invited women aged 40-74 years to service screening with mammography were compared with two counties where service screening started 5-7 years later. There were 109,000 and 77,000 women in the study and control counties, respectively., Methods: Cohorts in the study group were defined to include only breast cancer cases diagnosed after their first invitation to screening. Two outcome measures for breast cancer mortality were used; excess mortality and underlying cause of death (UCD). Detection mode was used to estimate the efficacy of screening for those women who actually attended screening. The cohorts were followed for 11 years., Results: The relative rate (RR) of breast cancer death as excess mortality and UCD for women aged 40-74 years invited to screening, compared with women not yet invited, was 0.70 (95% confidence interval [CI] 0.56-0.87) and 0.74 (95% CI 0.62-0.88), respectively. The largest effect was seen in women aged 40-49 years (RR = 0.64 and RR = 0.62 for excess mortality and UCD, respectively). RR in age 40-74 years for women actually screened was 0.65 (95% CI 0.51-0.84) and 0.70 (95% CI 0.57-0.86) for excess mortality and UCD, respectively. The number of women needed to screen to save one life was 912 after 11 years of follow-up., Conclusions: This study confirms previous findings in the earlier follow-up and indicates a long-term reduction of breast cancer mortality by 26-30%. The efficacy among those who actually attended screening was about 5% larger.

The aim of the present study was to relate the time trends in breast cancer incidence and mortality to the introduction of mammography screening in the Nordic capitals. Helsinki offered screening to women aged 50-59 starting in 1986. The other three capitals offered screening to women aged 50-69 starting in 1989 in Stockholm, 1991 in Copenhagen, and 1996 in Oslo. Prevalence peaks in breast cancer incidence depended on the age groups covered by the screening, the length of the implementation of screening, and the extent of background opportunistic screening. No mortality reduction following the introduction of screening was visible after seven to 12 years of screening in any of the three capitals where significant effects of the screening on the breast cancer mortality had already been demonstrated by using other analytical methods for the evaluation. No visible effect on mortality reduction was expected in Oslo due to too short an observation period. The study showed that the population-based breast cancer mortality trend is too crude a measure to detect the effect of screening on breast cancer mortality during the first years after the start of a programme.

Although incidence, mortality, and survival rates vary fourfold in the world's regions, in the world as a whole, the incidence of breast cancer is increasing, and in regions without early detection programs, mortality is also increasing. The growing burden of breast cancer in low-resource countries demands adaptive strategies that can improve on the too common pattern of disease presentation at a stage when prognosis is very poor. In January 2005, the Breast Health Global Initiative (BHGI) held its second summit in Bethesda, MD. The Early Detection and Access to Care Panel reaffirmed the core principle that a requirement at all resource levels is that women should be supported in seeking care and should have access to appropriate, affordable diagnostic tests and treatment. In terms of earlier diagnosis, the panel recommended that breast health awareness should be promoted to all women. Enhancements to basic facilities might include the following, in order of resources: effective training of relevant staff in clinical breast examination (CBE) both for symptomatic and asymptomatic women; opportunistic screening with CBE; demonstration projects or trials of organized screening using CBE or breast self-examination; and finally, feasibility studies of mammographic screening. Ideally, for complete evaluation, such projects require notification of deaths among breast cancer cases and staging of diagnosed tumors.

In 1989 the European Breast Cancer Network (EBCN) was established by the first pilot projects for breast cancer screening, co-funded by the Europe Against Cancer programme. We report early performance indicators for these EBCN projects while taking into account their organizational setting. Out of 17 projects in the network, 10 projects from six European countries contributed aggregated data on number of invitations, screening examinations, and breast cancers detected over the period 1989-2000. Results were summarized separately for projects in centralized versus decentralized health care environments. The European Guidelines for quality assurance in mammography screening provided reference values for the performance indicators. The most prominent finding in this study was the higher participation rate in centralized versus decentralized projects (average participation in 1998: 74 versus 33%; P<0.001), whereas the invitation system and screening policy in these projects were similar. Detection rates and characteristics of cancers detected at initial and subsequent screening examinations showed no significant differences between centralized and decentralized projects. Even though early performance indicators for centralized versus decentralized projects were similar, the impact of breast screening on mortality from this disease at the population level will differ since the decentralized projects reach only part of the target population.

The aim of this study was to analyse individual cases of lethal breast cancer and not to evaluate the screening programme. Women aged 40-74 years who were diagnosed with breast cancer in 1990-94 and died on or before 31 December 1998, during the gradual introduction of organised mammography service screening in north Sweden, were included in the study. Out of 342 breast cancer deaths, 280 (82%) were in symptomatic patients whose cancers were clinically detected. Most breast cancers that proved fatal were already in an advanced stage and/or of high histological grade at the time of detection. A shift towards a lower stage was seen among screen-detected and interval-detected fatal cases. In a few of the cases with fatal outcome, in patients primarily presenting with histological grade I tumours of various sizes or small screen-detected tumours less than 10mm in size, early diagnosis by mammography followed by state-of-the-art treatment did not seem to have been enough to prevent death.

In the current study the long-term effects of a pilot service screening programme in the Swedish county of Gävleborg were studied. Women aged 40-64 years in 13 sub-areas were followed from start of screening between 1974 and 1979. Two control groups were used for comparison; the neighbouring counties and all of Sweden. A reference period prior to the study period was used to facilitate an adjustment for possible differences in baseline breast cancer mortality. Only deaths from breast cancer diagnosed after the first invitation to screening were analysed. Two outcome measures were used for breast cancer mortality; the underlying cause of death and excess mortality. Using the neighbouring counties as a control group, the relative risk, after 22 years of follow-up, of 10 years of screening was estimated at 0.84 (95% CI 0.71-1.00) using excess mortality. Due to lead time bias the relative risk was overestimated by 4%. Hence, a significant 20% reduction of breast cancer excess mortality was found.

Background: Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening, some doubts have been expressed, and there is still uncertainty regarding the age specific effects., Methods: The authors report on a randomized, controlled trial of mammographic screening for breast carcinoma that was conducted among 51,611 women (21,650 women who were invited to a screening [the study group] and 29,961 women in a control group) ages 39-59 years in Gothenburg, Sweden. Among women in the study group, the screening interval was 18 months. The screening phase of the trial took place in 1982-1991, and follow-up for breast carcinoma mortality continued until December 31, 1996. Mortality from breast carcinoma was analyzed using a Poisson regression model. Overall and age specific effects of invitation to mammography screening on breast carcinoma mortality were calculated. Three mortality effects were estimated: the effect on deaths from breast tumors diagnosed during the screening phase of the trial, as assessed by an independent Endpoint Committee (the EPC evaluation model); the effect on deaths from breast carcinoma diagnosed during the screening phase of the trial, as determined by data from the National Cancer Registry and the National Cause of Death Register (the SCB evaluation model); and the effect on deaths from all breast carcinomas diagnosed up to December 31, 1996, as determined by the National Cancer Registry and the National Cause of Death Register (the SCB follow-up model)., Results: A nonsignificant, 21% reduction in the rate of mortality from breast carcinoma with invitation to screening was observed using the EPC evaluation model (relative risk [RR], 0.79; 95% confidence interval [95% CI], 0.58-1.08; P = 0.14); and a borderline significant, 23% rate reduction was observed using the SCB follow-up model (RR, 0.77; 95% CI, 0.60-1.00; P = 0.05). Age specific analyses yielded greater mortality rate reductions for the groups of women ages 39-44 years, 45-49 years, and 55-59 years, but there was no mortality rate reduction in the group of women ages 50-54 years. The effects of invitation to mammographic screening on the incidence of lymph node-positive disease closely paralleled the effects of invitation on breast carcinoma mortality. The effect on breast carcinoma mortality was consistent with the effect on all-cause mortality, suggesting no bias in classification of cause of death. Breast carcinoma incidence in the study group was almost identical to the incidence in the control group after trial by screening had ended in the control group (RR, 0.98; 95% CI, 0.88-1.09; P = 0.7)., Conclusions: The current results support the commonly observed 20-30% reduction in breast carcinoma mortality with invitation to screening. The impression that screening is less effective in women younger than 50 years may be an oversimplification. Age specific effects should be a target for further research., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11361)

Since the benefit of mammography screening for women 70 years and older is unclear, the aim of the present study was to evaluate the effect on breast cancer mortality of the population-based service-screening program in Sweden inviting women 70-74 years. Among the counties with service-screening programs in Sweden which started 1986-1990 those with upper age limit 74 years were compared to counties with 69 years as upper age limit with respect to refined breast cancer mortality. Allowance was made for potential biases namely inclusion of cases diagnosed before invitation and lead time. Two methods for estimation of breast cancer mortality were used; underlying cause of death (UCD) and excess mortality. With a mean follow-up of 10.1 years a reduction of the breast cancer excess mortality was estimated at 24%. Using the underlying cause of death the corresponding result was 6%. A non-significant reduction in breast cancer mortality was found in the counties with service-screening program including the age group 70-74 years in Sweden. The estimated reduction was larger when using excess mortality compared to the use of individual underlying cause of death.

Background: There has been much debate about the value of screening mammography. Here we update the overview of the Swedish randomised controlled trials on mammography screening up to and including 1996. The Kopparberg part of the Two-County trial was not available for the overview, but the continuation of the Malmö trial (MMST II) has been added. The article also contains basic data from the trials that have not been presented before. Methods The trials (n=247010, invited group 129750, control group 117260) have been followed up by record linkage to the Swedish Cancer and Cause of Death Registers. The relative risks (RR) for breast cancer death and mortality were calculated for the invited and the control groups. The trial-specific as well as the age-specific effects were analysed. RRs were calculated by the density method, with total person-time experience of the cohort by time interval of follow-up as a basis for estimating mortality rates. We calculated weighted RRs and 95% CI with the Mantel-Haenszel procedure., Findings: The median trial time-the time from randomisation until the first round was completed for the control group or if the control group was not invited, until end of follow-up-was 6.5 years (range 3.0-18.1). The median follow-up time, the time from randomisation, to the end of follow-up, was 15.8 years (5.8-20.2). There were 511 breast cancer deaths in 1864770 women-years in the invited groups and 584 breast cancer deaths in 1688440 women-years in the control groups, a significant 21% reduction in breast cancer mortality (RR=0.79, 95% CI 0.70-0.89). The reduction was greatest in the age group 60-69 years at entry (33%). Looking at 5-year age groups, there were statistically significant effects in the age groups 55-59, 60-64, and 65-69 years (RR=0.76, 0.68, and 0.69, respectively). There was a small effect in women 50-54 years at randomisation (RR=0.95). The benefit in terms of cumulative breast cancer mortality started to emerge at about 4 years after randomisation and continued to increase to about 10 years. Thereafter the benefit in absolute terms was maintained throughout the period of observation. The age-adjusted relative risk for the total mortality was 0.98 (0.96-1.00)., Interpretation: The advantageous effect of breast screening on breast cancer mortality persists after long-term follow-up. The recent criticism against the Swedish randomised controlled trials is misleading and scientifically unfounded.

Objectives: To estimate the effect of the population based service screening programme in Sweden on mortality from breast cancer among women aged 50-69. SETTING; In 1986, population based service screening with mammography started in Sweden, and by 1997 screening had been introduced in all counties. Half of the counties invite women from 40 years of age whereas women 50 and older are invited in the other counties. The upper age limit was either 69 or 74. Women in the age group 50-69 years are thus invited to screening in all counties., Methods: The counties which started with mammographic screening in 1986-87 constituted the study group and were compared with the counties which started in 1993 or later. In 1987 the mean number of women aged 50-69 was 161,986 and 98,608 in the study and control groups, respectively. Refined excess mortality (smoothed with the Lowess method) from breast cancer and refined cause specific mortality from breast cancer were used as effect measures. To adjust for geographical differences in mortality from breast cancer a reference period was used. Allowance was made for two potential biases: (a) inclusion bias implying the inclusion of cases diagnosed before invitation to screening in the first screening round, and (b) lead time bias., Results: After a mean follow up time of 10.6 years since the start of screening and a mean individual follow up time of 8.4 years, a non-significant reduction in refined excess mortality for breast cancer was estimated as relative risk (RR) 0.84 (95% confidence interval (95% CI) 0.67 to 1.05). After adjustment for inclusion and lead time biases the RR was 0.80 (20% reduction). Only 27% of the deaths from breast cancer in the total mortality for women aged 50-79 at death consisted of women aged 50-69 at diagnosis who were diagnosed after the start of screening. This figure has important implications for judgement of the impact of screening on age specific national breast cancer mortalities., Conclusions: A non-significant reduction in mortality from breast cancer was found in counties performing service screening with mammography in Sweden. Adjustment for possible biases changed the result towards a larger effect of screening. The results do not contradict the effects found in the Swedish randomised mammography trials.

The aim of the study was to develop a model for estimating the effect of the nation-wide service screening program with mammography on breast cancer mortality in Sweden. In 1997, the introduction of population-based service screening had been completed in all 26 counties. In approximately half of the counties suitable for evaluation, the lower age limit for invitation was 40 years (study population) and in the other half the age limit was 50 years (control population). The numbers of females aged 40 49 years for the two populations were 202,152 and 237,279, respectively (1988). The study and control populations were compared for the period 1986-1996 with regard to refined breast cancer mortality. To adjust for geographical differences, the period 1976 1986 was used as reference. With a mean follow-up time of 8 years, the estimated relative risk of breast cancer death in relation to invitation to service screening among women aged 40-49 years at breast cancer diagnosis was 0.91 (95% confidence interval 0.72-1.15). These findings were compatible with those presented in the previous overview of the Swedish randomized studies.

The purpose of this overview is to estimate more precisely the long-term effect of mammography screening by adding four more years of follow-up to women aged 40-49 years in the four Swedish trials on mammography screening. Data from the four, trials were merged and linked to the Swedish Cancer and Cause of Death Register for 1958-1993 and 1951-1993 respectively to identify date of breast cancer diagnosis and cause and date of death. The invited and control groups comprised 48,569 and 40,247 women respectively. At the December 1993 follow-up, 602 and 482 breast cancer cases were identified in the two groups respectively, of which 104 and 111 had breast cancer as the underlying cause of death. This corresponds to a relative risk (RR) of 0.77 (95% CI: 0.59-1.01) for the two groups. In the 40-44 age group at randomization, 94% of breast cancer patients in the study and 89% in the control group were diagnosed before the age of 50; however, among breast cancer deaths in this age group, only two in the invited and five in the control group died after age 50. At follow-up of women 40-44 years at randomization 208 women in the invited and 184 in the control group were reported to the Cancer registry with breast cancer. Out of these 195 (94%) and 163 (89%) respectively were reported before the age of 50. Further, the relative risk for the age group 40-44 years at randomization by age at follow-up was 1.11, 0.51 and 0.46 for the age groups 45-49, 50-54, and 55-59 at follow-up. This study shows a 23% reduction in the breast cancer mortality in women 40-49 years at randomization achieved from a median trial time of 7.0 years, a median follow-up time of 12.8 years, and a screening interval of 18-24 months. Almost all of the effect in the 40-44 year age group at randomization was due to screening before the age of 50.

Objective: To apply an indirect method for estimation of the breast cancer related excess mortality in the Swedish randomised mammography screening trials., Setting: Randomised trials on mammography screening have, in Sweden, been performed in the counties of Kopparberg (W) and Ostergötland (E), the so called WE study, and in the three largest cities in Sweden, Stockholm (southern part), Gothenburg, and Malmö. An overview of the trials was presented in the Lancet in 1993 and included 156,911 women in the invited group and 125,866 in the control group., Methods: The excess mortality in the breast cancer subgroups was estimated by indirect standardisation using official national cause of death statistics according to Statistics Sweden as a reference., Results: The estimated reduction of the breast cancer related mortality was 24% for the whole group (40-74 years at randomisation). The corresponding figures for the age groups 40-49, 50-59, and 60-69 years were 6%, 28%, and 34% respectively., Conclusion: The results are very similar to those presented earlier based on the traditional comparison of the breast cancer mortality in the invited and in the control group. This analysis further strengthens previous reports on a beneficial effect of mammography screening, which is especially pronounced in the age group 50-69.

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.

Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282,777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Ostergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation ("breast cancer as underlying cause of death" or "breast cancer present at death"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact.