Overdiagnosis Of Breast Cancer Research Articles

A Year in Review in Long-Term Care: Virtual Reality, Breast Cancer Overdiagnosis, and Decolonization Interventions in Nursing Homes

A Year in Review in Long-Term Care: Virtual Reality, Breast Cancer Overdiagnosis, and Decolonization Interventions in Nursing Homes

The influence of breast screening on breast cancer incidence in England: observational study based on cancer registries and bulletins of the NHS Breast Screening Programme.

To assess the amount of breast cancer overdiagnosis associated with the National Health Service Breast Screening Programme (NHSBSP) that started in 1988 in England. First, numbers of breast cancers in women eligible for breast screening not attending screening were estimated for the period 1995-2019, which were extrapolated to all women. A second method was based on ratios of incidence rates of breast cancers in women aged 50-69 to women aged 70 years or more in 1971-1985. The ratio was used for estimating expected numbers of cancers in 1988-2019, and 1995-2019. From 1995 to 2019, 506,607 non-invasive and invasive breast cancers were diagnosed among women aged 50-64 years (1995-2001) and 50-70 years (2002-2019). A first method estimated that 95,297 cancers were in excess to the number of cancers that would be expected had the NHSBSP not existed. 42,567 screen-detected non-invasive and micro-invasive cancers represented 45.8% of the total excess cancer. 18.8% of all cancers diagnosed among women invited to screening, 25.1% of cancers found in women attending screening, and 35.1% of cancers detected by screening would represent overdiagnosis. A second method estimated that, 18.0% of all cancers diagnosed in 1988-2019, and 18.2% of all cancers diagnosed in 1995-2019 among women invited to screening would represent overdiagnosis. The two independent methods obtained similar estimates of overdiagnosis. The NHS Breast Screening Programme in England is associated with substantial amount of overdiagnosis.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Estimating Breast Cancer Overdiagnosis After Screening Mammography Among Older Women in the United States.

Overdiagnosis is increasingly recognized as a harm of breast cancer screening, particularly for older women. To estimate overdiagnosis associated with breast cancer screening among older women by age. Retrospective cohort study comparing the cumulative incidence of breast cancer among older women who continued screening in the next interval with those who did not. Analyses used competing risk models, stratified by age. Fee-for-service Medicare claims, linked to the SEER (Surveillance, Epidemiology, and End Results) program. Women 70 years and older who had been recently screened. Breast cancer diagnoses and breast cancer death for up to 15 years of follow-up. This study included 54 635 women. Among women aged 70 to 74 years, the adjusted cumulative incidence of breast cancer was 6.1 cases (95% CI, 5.7 to 6.4) per 100 screened women versus 4.2 cases (CI, 3.5 to 5.0) per 100 unscreened women. An estimated 31% of breast cancer among screened women were potentially overdiagnosed. For women aged 75 to 84 years, cumulative incidence was 4.9 (CI, 4.6 to 5.2) per 100 screened women versus 2.6 (CI, 2.2 to 3.0) per 100 unscreened women, with 47% of cases potentially overdiagnosed. For women aged 85 and older, the cumulative incidence was 2.8 (CI, 2.3 to 3.4) among screened women versus 1.3 (CI, 0.9 to 1.9) among those not, with up to 54% overdiagnosis. We did not see statistically significant reductions in breast cancer-specific death associated with screening. This study was designed to estimate overdiagnosis, limiting our ability to draw conclusions on all benefits and harms of screening. Unmeasured differences in risk for breast cancer and differential competing mortality between screened and unscreened women may confound results. Results were sensitive to model specifications and definition of a screening mammogram. Continued breast cancer screening was associated with greater incidence of breast cancer, suggesting overdiagnosis may be common among older women who are diagnosed with breast cancer after screening. Whether harms of overdiagnosis are balanced by benefits and for whom remains an important question. National Cancer Institute.

Benefits and harms of breast cancer screening: Cohort study of breast cancer mortality and overdiagnosis.

Quantifying the benefits and harms of breast cancer screening accurately is important for planning and evaluating screening programs and for enabling women to make informed decisions about participation. However, few cohort studies have attempted to estimate benefit and harm simultaneously. We aimed to quantify the impact of mammographic screening on breast cancer mortality and overdiagnosis using a cohort of women invited to attend Australia's national screening program, BreastScreen. In a cohort of 41,330 women without prior breast cancer diagnosis, screening, or diagnostic procedures invited to attend BreastScreen Western Australia in 1994-1995, we estimated the cumulative risk of breast cancer mortality and breast cancer incidence (invasive and ductal carcinoma in situ) from age 50 to 85 years for attenders and non-attenders. Data were obtained by linking population-based state and national health registries. Breast cancer mortality risks were estimated from a survival analysis that accounted for competing risk of death from other causes. Breast cancer risk for unscreened women was estimated by survival analysis, while accounting for competing causes of death. For screened women, breast cancer risk was the sum of risk of being diagnosed at first screen, estimated using logistic regression, and risk of diagnosis following a negative first screen estimated from a survival analysis. For every 1,000 women 50 years old at first invitation to attend BreastScreen, there were 20 (95% CI 12-30) fewer breast cancer deaths and 25 (95% CI 15-35) more breast cancers diagnosed for women who attended than for non-attendees by age 85. Of the breast cancers diagnosed in screened women, 21% (95% CI 13%-27%) could be attributed to screening. The estimated ratio of benefit to harm was consistent with, but slightly less favourable to screening than most other estimates from cohort studies. Women who participate in organised screening for breast cancer in Australia have substantially lower breast cancer mortality, while some screen-detected cancers may be overdiagnosed.

Reassessing the Benefits and Harms of Risk-Reducing Medication Considering the Persistent Risk of Breast Cancer Mortality in Estrogen Receptor-Positive Breast Cancer.

Recent studies, including a meta-analysis of 88 trials, have shown higher than expected rates of recurrence and death in hormone receptor-positive breast cancer. These new findings suggest a need to re-evaluate the use of risk-reducing medication to avoid invasive breast cancer and breast cancer death in high-risk women. We adapted an established Cancer Intervention and Surveillance Modeling Network model to evaluate the lifetime benefits and harms of risk-reducing medication in women with a ≥ 3% 5-year risk of developing breast cancer according to the Breast Cancer Surveillance Consortium risk calculator. Model input parameters were derived from meta-analyses, clinical trials, and large observational data. We evaluated the effects of 5 years of risk-reducing medication (tamoxifen/aromatase inhibitors) with annual screening mammography ± magnetic resonance imaging (MRI) compared with no screening, MRI, or risk-reducing medication. The modeled outcomes included invasive breast cancer, breast cancer death, side effects, false positives, and overdiagnosis. We conducted subgroup analyses for individual risk factors such as age, family history, and prior biopsy. Risk-reducing tamoxifen with annual screening (± MRI) decreased the risk of invasive breast cancer by 40% and breast cancer death by 57%, compared with no tamoxifen or screening. This is equivalent to an absolute reduction of 95 invasive breast cancers, and 42 breast cancer deaths per 1,000 high-risk women. However, these drugs are associated with side effects. For example, tamoxifen could increase the number of endometrial cancers up to 11 per 1,000 high-risk women. Benefits and harms varied by individual characteristics. The addition of risk-reducing medication to screening could further decrease the risk of breast cancer death. Clinical guidelines for high-risk women should consider integrating shared decision making for risk-reducing medication and screening on the basis of individual risk factors.

A case-control study to evaluate the impact of the breast screening programme on breast cancer incidence in England.

There is uncertainty about overdiagnosis in mammography screening. We aimed to estimate the effect of screening on breast cancer incidence and overdiagnosis in the NHS Breast Screening Programme in England. The study included 57,493 cases and 105,653 controls, with cases defined as women diagnosed at ages 47-89 with primary breast cancer, invasive or ductal carcinoma in situ, in 2010 or 2011. Where possible, two controls were selected per case, matched on date of birth and screening area. Conditional logistic regression was used to estimate the effect of screening on breast cancer risk, with adjustment for potential self-selection bias. Results were combined with national incidence data to estimate absolute rates of overdiagnosis. Overdiagnosis was calculated as the cumulative excess of cancers diagnosed in the age group 50-77 in a woman attending three-yearly screening between ages 50 and 70 compared with a woman attending no screens. The estimated number of cases overdiagnosed in women attending all screens in the programme was 679.3 per 100,000 without adjustment for self-selection bias and 261.2 per 100,000 with adjustment. These corresponded to an estimated 9.5% of screen-detected cancers overdiagnosed without adjustment and 3.7% with adjustment for self-selection. The NHS Breast Screening Programme in England confers at worst modest levels of overdiagnosis.

Overdiagnosis of invasive breast cancer in population-based breast cancer screening: A short- and long-term perspective

BackgroundOverdiagnosis of invasive breast cancer (BC) is a contentious issue. ObjectiveThe aim of this paper is to estimate the overdiagnosis rate of invasive BC in an organised BC screening program and to evaluate the impact of age and follow-up time. MethodsThe micro-simulation model SiMRiSc was calibrated and validated for BC screening in Flanders, where women are screened biennially from age 50 to 69. Overdiagnosis rate was defined as the number of invasive BC that would not have been diagnosed in the absence of screening per 100,000 screened women during the screening period plus follow-up time (which was set at 5 years and varied from 2 to 15 years). Overdiagnosis rate was calculated overall and stratified by age. ResultsThe overall overdiagnosis rate for women screened biennially from 50 to 69 was 20.1 (95%CI: 16.9–23.2) per 100,000 women screened at 5-year follow-up from stopping screening. Overdiagnosis at 5-year follow-up time was 12.9 (95%CI: 4.6–21.1) and 74.2 (95%CI: 50.9–97.5) per 100,000 women screened for women who started screening at age 50 and 68, respectively. At 2- and 15-year follow-up time, overdiagnosis rate was 98.5 (95%CI: 75.8–121.3) and 13.4 (95%CI: 4.9–21.9), respectively, for women starting at age 50, and 297.0 (95%CI: 264.5–329.4) and 34.2 (95%CI: 17.5–50.8), respectively, for those starting at age 68. ConclusionsSufficient follow-up time (≥10 years) after screening stops is key to obtaining unbiased estimates of overdiagnosis. Overdiagnosis of invasive BC is a larger problem in older compared to younger women.

Effects of awareness of breast cancer overdiagnosis among women with screen-detected or incidentally found breast cancer: a qualitative interview study

ObjectivesTo explore experiences of women who identified themselves as having a possible breast cancer overdiagnosis.DesignQualitative interview study using key components of a grounded theory analysis.SettingInternational interviews with women diagnosed with...

Harms and Benefits of Mammography Screening

Mammography is one of the most technically challenging areas of radiography, required high spatial resolution, excellent soft tissue contrast and low radiation dose. Mammography screening for breast cancer is worldwide available. Early detection of breast cancer through screening can lower breast cancer mortality rate and reduce the burden of this disease in the population, the benefits and harms of mammography screening have been debated in the past years. This review discuss the benefits and harms of mammography screening in light of findings from randomized trials and more recent observational studies performed in the era of modern diagnosis. The main benefit for mammography screening is reduces the risk of dying from breast cancer. Reduction vary from 15 to 20% in randomized trials to more recent estimates of 13 to 17% in analyses of observational studies. UK data of 2007 shows that for 1,000 women invited to biennial mammography screening for 20years to 50years age, 2-3 women’s are prevented from breast cancer. Main harm of mammography screening is the over diagnosis of breast cancer. 15 women’s over diagnosis for every 1000 women invited to biennial screening for 20 years from 50 years age. In an era of limiting health care services, screening services need to scrutinized and compared with each other regard to effectiveness, cost effectiveness and harms.

A new perspective on breast cancer diagnostic guidelines to reduce overdiagnosis.

Overdiagnosis of breast cancer, defined as diagnosing a cancer that would otherwise not cause symptoms or death in a patient's lifetime, costs U.S. health care system over $1.2 billion annually. Overdiagnosis rates, estimated to be around 10%–40%, may be reduced if indolent breast findings can be identified and followed with noninvasive imaging rather than biopsy. However, there are no validated guidelines for radiologists to decide when to choose imaging options recognizing cancer grades and types. The aim of this study is to optimize breast cancer diagnostic decisions based on cancer types using a large‐scale finite‐horizon Markov decision process (MDP) model with 4.6 million states to help reduce overdiagnosis. We prove the optimality of a divide‐and‐search algorithm that relies on tight upper bounds on the optimal decision thresholds to find an exact optimal solution. We project the high‐dimensional MDP onto two lower dimensional MDPs and obtain feasible upper bounds on the optimal decision thresholds. We use real data from two private mammography databases and demonstrate our model performance through a previously validated simulation model that has been used by the policy makers to set the national screening guidelines in the United States. We find that a decision‐analytical framework optimizing diagnostic decisions while accounting for breast cancer types has a strong potential to improve the quality of life and alleviate the immense costs of overdiagnosis. Our model leads to a 20% reduction in overdiagnosis on the screening population, which translates into an annual savings of approximately $300 million for the U.S. health care system.

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.

Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis. To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer. Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening. Breast Cancer Surveillance Consortium (BCSC) facilities. Women aged 50 to 74 years at first mammography screen between 2000 and 2018. Screening mammograms and screen-detected or interval breast cancer. The cohort included 35986 women, 82677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis. Exclusion of women with first mammography screen outside BCSC. On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening. National Cancer Institute.

Abstract GS4-06: Estimation of breast cancer overdiagnosis in a US breast screening cohort

Abstract Background. Breast cancer screening is subject to overdiagnosis, that is the mammographic detection of cancers that would not become symptomatic or otherwise cause harm in the absence of screening. The risk of overdiagnosis associated with screening mammography is a concern but there is no consensus about its magnitude. Estimates based on excess incidence are prone to bias, and estimates based on models have been criticized for not explicitly accommodating indolent tumors. Methods. We obtained individual mammography screening and breast cancer diagnosis records from the Breast Cancer Surveillance Consortium (BCSC), an authoritative data source in the US. Women aged 50-74 years who had their first mammogram in the BCSC between 2000-2018 were included. We fit a mathematical model that accounts for the transition from healthy to preclinical and clinical disease while allowing for a fraction of indolent preclinical tumors. We performed Bayesian inference using the Hamiltonian Monte Carlo sampler Stan to estimate model parameters and predict overdiagnosis rates under biennial and annual screening between ages 50 and 74. We defined the breast cancer overdiagnosis rate as the fraction of screen-detected cancers that would not have been symptomatically detected in the woman’s remaining lifetime. Overdiagnosis arises from two possible scenarios: the screen-detection of indolent cancers, and the screen-detection of progressive cancers that do not progress to clinical disease before the woman dies from causes unrelated to breast cancer. To calculate the second contribution, we determined the risk of other-cause death using age-cohort-adjusted annual mortality risks. Results. The analytic cohort included 35,986 women, 82,677 screens and 718 breast cancer diagnoses. The mean fraction of indolent cancers among all preclinical cases (detected and undetected) was 3.6% (95% credible interval [CI]: 0.2% to 13.8%), the mean preclinical sojourn time was 6.5 years (CI: 4.9 to 8.6) and the mean test sensitivity was 81.7% (CI: 72.6% to 89.0%). For a program of biennial screening from age 50 to 74, the predicted overdiagnosis rate among screen-detected cases was 15.3% (95% prediction interval [PI]: 9.7% to 25.2%), where 6.0% (PI: 0.2% to 19.0%) was due to the detection of indolent cancers and 9.3% (PI: 5.8%-13.6%) was due to competing mortality. For a program of annual screening from age 50 to 74, the overall predicted overdiagnosis rate was 14.6% (PI: 9.4% to 23.9%). Discussion. Our results indicate that overdiagnosis among screen-detected cancers is less frequent than estimated by excess-incidence studies and more frequent than estimated by previous modeling studies that did not account for indolent tumors. Citation Format: Marc D Ryser, Jane Lange, Lurdes Inoue, Ellen S O'Meara, Charlotte Gard, Diana L Miglioretti, Jean-Luc Bulliard, Andrew F Brouwer, E. Shelley Hwang, Ruth B Etzioni. Estimation of breast cancer overdiagnosis in a US breast screening cohort [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-06.

A Procedure for Eliciting Women's Preferences for Breast Cancer Screening Frequency.

BackgroundWe evaluate the construct validity of a proposed procedure for eliciting lay preferences among health care policy options, suited for structured surveys. It is illustrated with breast cancer screening, a domain in which people may have heterogeneous preferences.MethodsOur procedure applies behavioral decision research principles to eliciting preferences among policy options expressed in quantitative terms. Three-hundred women older than 18 y without a history of breast cancer were recruited through Amazon MTurk. Participants evaluated 4 screening options for each of 4 groups of women, with varying risk of breast cancer. Each option was characterized by estimates of 3 primary outcomes: breast cancer deaths, false alarms, and overdiagnosis resulting in unnecessary treatment of cancers that would not progress. These estimates were based on those currently being developed by the Breast Cancer Surveillance Consortium. For each risk group, participants stated how frequently they would wish to receive screening, if the predicted outcomes applied to them.ResultsA preregistered test found that preferences were robust enough to be unaffected by the order of introducing and displaying the outcomes. Other tests of construct validity also suggested that respondents generally understood the task and expressed consistent preferences. Those preferences were related to participants’ age and mammography history but not to measures of their numeracy, subjective numeracy, or demographics. There was considerable heterogeneity in their preferences.ConclusionsMembers of the public can be engaged more fully in informing future screening guidelines if they evaluate the screening options characterized by the expected health outcomes expressed in quantitative terms. We offer and evaluate such a procedure, in terms of its construct validity with a diverse sample of women.HighlightsA novel survey method for eliciting lay preferences for breast cancer screening is proposed and evaluated in terms of its construct validity.Participants were generally insensitive to irrelevant task features (e.g., order of presentation) and sensitive to relevant ones (e.g., quantitative estimates of breast cancer risk, harms from screening).The proposed method elicits lay preferences in terms that can inform future screening guidelines, potentially improving communication between the public and policy makers.

Women’s conceptual knowledge about breast cancer screening and overdiagnosis in Norway: a cross-sectional study

ObjectiveTo investigate conceptual knowledge about mammographic screening among Norwegian women.DesignWe administered a cross-sectional, web-based survey. We used multiple-choice questions and a grading rubric published by a research group from Australia.SettingOur...

Are advancements in screening technology contributing to breast cancer over-diagnosis?

Advancements in breast screening technology have increased the sensitivity of screening and thereby increased the detection rates of nonlethal cancers. Thus, improvements in breast screening technology may contribute to 'over-diagnosis', which refers to detection of cancers that pose no threat to life and that, in the absence of screening, might never have been detected. The purpose of this review is to draw attention to risks of over-diagnosis and provide a rationale for evaluating screening clinical breast examination (CBE) as an alternative to modern technology-based (mammography) screening. Novel screening technologies have been adopted largely on the basis of their abilities to increase tumor-detection rates. However, as breast cancer treatments have improved, the mortality benefits of screening have declined. Moreover, there is evidence suggesting that, in the modern era of effective adjuvant systemic therapies, the mortality benefit of screening CBE may now be comparable to that of modern screening mammography, but screening CBE carries less risk of over-diagnosis. A randomized trial comparing modern mammography screening versus screening CBE is warranted. If confirmed that the mortality benefits of the two screening strategies are now comparable, then screening CBE might be considered a reasonable alternative to mammography screening.

Breast cancer screening and overdiagnosis.

Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow-up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis.

Women's perception, preconceptions, and information preferences for the limitations of breast cancer screening and overdiagnosis: a think-aloud study on the new information materials of the Agency for Health Protection of the Metropolitan Area of Milan

communicating breast cancer screening (BCS) limits and overdiagnosis implies providing complete and balanced information to allow informed decision-making. to describe women's perceptions, preconceptions, and information preferences regarding the breast cancer screening (BCS) programme paper and web information materials of the Agency for Health Protection of the Metropolitan Area of Milan (Lombardy Region, Northern Italy). qualitative, descriptive study. participants' voluntary recruitment took place in the registration departments of three hospitals. Participants were purposively recruited based on sociodemographic characteristics of the target population of the programme (44 women aged 40-74 years, living in the Metropolitan Area of Milan). In each material type subgroup, different health literacy levels and age classes were included, until thematic saturation was reached. thematic analysis of qualitative data collected during think-aloud interviews. the thematic analysis identified 5 main themes: 1. validation of the information reported in the materials, according to the interviewees' personal experiences;2. information preferences of particular subgroups of women, which led to a tailored approach for the web materials;3. negative emotions elicited while receiving information regarding BCS limits, which guided the rewriting of certain definitions; 4. disproportioned risk perception, with greater weight attributed to the risk of false negative results than the risk of overdiagnosis; 5. organizational preferences regarding the type and frequency of the provided tests and the age limits of the programme. in the present sample of women living in the Metropolitan Area of Milan, knowledge and comprehension of overdiagnosis are scarce. The main reasons for distrust in the BCS programme rely on the preexisting beliefs regarding the most appropriate tests and age limits. These beliefs were established from previously received information, inconsistent with that officially provided by the programme.

Breast cancer mortality and overdiagnosis after implementation of population-based screening in Denmark

IntroductionService breast cancer screening is difficult to evaluate because there is no unscreened control group. Due to a natural experiment, where 20% of women were offered screening in two regions up to 17 years before other women, Denmark is in a unique position. We utilized this opportunity to assess outcome of service screening.Materials and methodsScreening was offered in Copenhagen from 1991 and Funen from 1993 to women aged 50–69 years. We used difference-in-differences methodology with a study group offered screening; a historical control group; a regional control group; and a regional–historical control group, comparing breast cancer mortality and incidence, including ductal carcinoma in situ, between study and historical control group adjusted for changes in other regions, and calculating ratios of rate ratios (RRR) with 95% confidence intervals (CI). Data came from Central Population Register; mammography screening databases; Cause of Death Register; and Danish Cancer Register.ResultsFor breast cancer mortality, the study group accumulated 1,551,465 person-years and 911 deaths. Long-term breast cancer mortality in Copenhagen was 20% below expected in absence of screening; RRR 0.80 (95% CI 0.71–0.90), and in Funen 22% below; RRR 0.78 (95% CI 0.68–0.89). Combined, cumulative breast cancer incidence in women followed 8+ years post-screening was 2.3% above expected in absence of screening; RRR 1.023 (95% CI 0.97–1.08).DiscussionBenefit-to-harm ratio of the two Danish screening programs was 2.6 saved breast cancer deaths per overdiagnosed case. Screening can affect only breast cancers diagnosed in screening age. Due to high breast cancer incidence after age 70, only one-third of breast cancer deaths after age 50 could potentially be affected by screening. Increasing upper age limit could be considered, but might affect benefit-to-harm ratio negatively.