Meta-analysis of breast cancer mortality benefit and overdiagnosis adjusted for adherence: improving information on the effects of attending screening mammography.
ABSTRACT: Women require information about the impact of regularly attending screening mammography on breast cancer mortality and overdiagnosis to make informed decisions. To provide this information we aimed to meta-analyse randomised controlled trials adjusted for adherence to the trial protocol.Nine screening mammography trials used in the Independent UK Breast Screening Report were selected. Extending an existing approach to adjust intention-to-treat (ITT) estimates for less than 100% adherence rates, we conducted a random-effects meta-analysis. This produced a combined deattenuated prevented fraction and a combined deattenuated percentage risk of overdiagnosis.In women aged 39-75 years invited to screen, the prevented fraction of breast cancer mortality at 13-year follow-up was 0.22 (95% CI 0.15-0.28) and it increased to 0.30 (95% CI 0.18-0.42) with deattenuation. In women aged 40-69 years invited to screen, the ITT percentage risk of overdiagnosis during the screening period was 19.0% (95% CI 15.2-22.7%), deattenuation increased this to 29.7% (95% CI 17.8-41.5%).Adjustment for nonadherence increased the size of the mortality benefit and risk of overdiagnosis by up to 50%. These estimates are more appropriate when developing quantitative information to support individual decisions about attending screening mammography.
Project description:Objective To analyse stage specific incidence of breast cancer in the Netherlands where women have been invited to biennial mammography screening since 1989 (ages 50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality and quantified overdiagnosis.Design Population based study.Setting Mammography screening programme, the Netherlands.Participants Dutch women of all ages, 1989 to 2012.Main outcome measures Stage specific age adjusted incidence of breast cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours associated with screening were estimated by comparing rates in women aged 50-74 with those in age groups not invited to screening. Overdiagnosis was estimated after subtraction of the lead time cancers. Breast cancer mortality reductions and overdiagnosis during 2010-12 were computed without (scenario 1) and with (scenario 2) a cohort effect on mortality secular trends.Results The incidence of stage 2-4 breast cancers in women aged 50 or more was 168 per 100?000 in 1989 and 166 per 100?000 in 2012. Screening would be associated with a 5% mortality reduction in scenario 1 and with no influence on mortality in scenario 2. In both scenarios, improved treatments would be associated with 28% reductions in mortality. Overdiagnosis has steadily increased over time with the extension of screening to women aged 70-75 and with the introduction of digital mammography. After deduction of clinical lead time cancers, 33% of cancers found in women invited to screening in 2010-12 and 59% of screen detected cancers would be overdiagnosed.Conclusions The Dutch mammography screening programme seems to have little impact on the burden of advanced breast cancers, which suggests a marginal effect on breast cancer mortality. About half of screen detected breast cancers would represent overdiagnosis.
Project description:The benefits and harms of population-wide mammography screening have been long debated. This study evaluated the impact of screening frequency and age range on breast cancer mortality reduction and overdiagnosis.We developed a Markov simulation model for the evaluation of mammography screening in a cohort of British women born in 1935-40.For triennial screening in women aged 47-73, breast cancer mortality reduction and overdiagnosis was 18.1% (95% confidence interval: 17.3%, 19.0%) and 5.6% (5.1%, 6.1%), of all breast cancer deaths and diagnoses, respectively, from age 40 to 85 years. For annual screening in the same age range, estimates for both outcomes increased considerably to 35.0% (34.2%, 35.7%) and 7.6% (7.1%, 8.1%), respectively. For the age extension of triennial screening from 50-70 to 47-73, we estimated 5 (3, 7) incremental breast cancer deaths avoided and 14 (9, 19) incremental cases overdiagnosed per 10?000 women invited for screening.Estimates of mortality reduction and overdiagnosis were highly dependent on screening frequency, age range, and uptake, which may explain differences between some previous estimates obtained from randomised trials and from service screening.
Project description:BACKGROUND: Overdiagnosis is the most important adverse event of breast cancer screening with the estimates ranging from 0% to 40-50% depending on invitational age and methods. We updated the estimates of overdiagnosis in Helsinki service screening study in Finland by comparing the observed and expected cumulative incidence of all breast carcinomas and invasive breast carcinomas. METHODS: Women aged 50-59 years have been invited to Helsinki service screening since 1986. The incidence of breast carcinoma in the first invited birth cohorts born in 1935-1939 was compared with older, non-invited cohorts. The minimum follow-up time of the invitees after the last screening round was 14 years. Expected cumulative incidence rates were estimated with two alternative approaches. RESULTS: For both any breast carcinoma and invasive breast carcinoma, the estimates of overdiagnosis varied from 5% (95% CI=-1, 11%) to 7% (95% CI=1, 13%) depending on the approach. CONCLUSIONS: Our estimates of overdiagnosis are of the same magnitude than other plausible estimates in Europe. Both alternative approaches produced similar estimates for the expected cumulative incidence, which increased the confidence in the estimates of overdiagnosis.
Project description:To evaluate the effectiveness of contemporary mammography screening using individual information about screening history and breast cancer mortality from public screening programmes.Prospective cohort study of Norwegian women who were followed between 1986 and 2009. Within that period (1995-2005), a national mammography screening programme was gradually implemented, with biennial invitations sent to women aged 50-69 years.All Norwegian women aged 50-79 between 1986 and 2009.Multiple Poisson regression analysis was used to estimate breast cancer mortality rate ratios comparing women who were invited to screening (intention to screen) with women who were not invited, with a clear distinction between cases of breast cancer diagnosed before (without potential for screening effect) and after (with potential for screening effect) the first invitation for screening. We took competing causes of death into account by censoring women from further follow-up who died from other causes. Based on the observed mortality reduction combined with the all cause and breast cancer specific mortality in Norway in 2009, we used the CISNET (Cancer Intervention and Surveillance Modeling Network) Stanford simulation model to estimate how many women would need to be invited to biennial mammography screening in the age group 50-69 years to prevent one breast cancer death during their lifetime.During 15 193 034 person years of observation (1986-2009), deaths from breast cancer occurred in 1175 women with a diagnosis after being invited to screening and 8996 women who had not been invited before diagnosis. After adjustment for age, birth cohort, county of residence, and national trends in deaths from breast cancer, the mortality rate ratio associated with being invited to mammography screening was 0.72 (95% confidence interval 0.64 to 0.79). To prevent one death from breast cancer, 368 (95% confidence interval 266 to 508) women would need to be invited to screening.Invitation to modern mammography screening may reduce deaths from breast cancer by about 28%.
Project description:The aim of this study was the evaluation of the impact of service screening programmes on breast cancer mortality in five regions of Italy. We conducted a matched case-control study with four controls for each case. Cases were defined as breast cancer deaths occurred not later than 31 December 2002. Controls were sampled from the local municipality list and matched by date of birth. Screening histories were assessed by the local, computerised, screening database and subjects were classified as either invited or not-yet-invited and as either screened or unscreened. There were a total of 1750 breast cancer deaths within the 50 to 74-year-old breast cancer cases and a total of 7000 controls. The logistic conditional estimate of the cumulative odds ratios comparing invited with not-yet-invited women was 0.75 (95% CI: 0.62-0.92). Restricting the analyses to invited women, the odds ratio of screened to never-respondent women corrected for self-selection bias was 0.55 (95% CI: 0.36-0.85). The introduction of breast cancer screening programmes in Italy is associated with a reduction in breast cancer mortality attributable to the additional impact of service screening over and above the background access to mammography.
Project description:OBJECTIVES:Informed decisions about cancer screening require accurate knowledge regarding cancer risks and screening. This study investigates: (1) European women's knowledge of their risk of developing breast, ovarian, cervical or endometrial cancer, (2) their knowledge about mammography screening and (3) whether an evidence-based leaflet improves their knowledge. DESIGN:Cross-sectional online intervention survey. SETTING:National samples from five European countries (Czech Republic, Germany, UK, Italy and Sweden)-drawn from the Harris Interactive and the Toluna panel, respectively, in January 2017-were queried on their knowledge of age-specific risks of developing breast, cervical, ovarian or endometrial cancer within the next 10 years and of mammography screening before and after intervention. PARTICIPANTS:Of 3629 women (inclusion criteria: age 40-75 years) invited, 2092 responded and 1675 completed the survey (response rate: 61.4%). INTERVENTION:Evidence-based leaflet summarising information on age-adjusted female cancer risks, mammography and aspects of cancer prevention. PRIMARY OUTCOME MEASURES:Proportion of women (1) accurately estimating their risk of four female cancers, (2) holding correct assumptions of mammography screening and (3) changing their estimations and assumptions after exposure to leaflet. FINDINGS:Across countries, 59.2% (95% CI 56.8% to 61.6%) to 91.8% (95% CI 90.3% to 93.0%) overestimated their female cancer risks 7-33 fold (mediansacross?tumours: 50.0 to 200.0). 26.5% (95% CI 24.4% to 28.7%) were aware that mammography screening has both benefits and harms. Women who accurately estimated their breast cancer risk were less likely to believe that mammography prevents cancer (p<0.001). After leaflet intervention, knowledge of cancer risks improved by 27.0 (95% CI 24.9 to 29.2) to 37.1 (95% CI 34.8 to 39.4) percentage points and of mammography by 23.0 (95% CI 21.0 to 25.1) percentage points. CONCLUSION:A considerable number of women in five European countries may not possess the prerequisites for an informed choice on cancer screening. Evidence-based information in patient leaflets can improve this situation.
Project description:Breast cancer is the most prevalent cancer among women and mammography screening programs are seen as a key strategy to reduce breast cancer mortality. In Germany, women are invited to the population-based mammography screening program between ages 50 to 69. It is still discussed whether the benefits of mammography screening outweigh its harms. Therefore, the concept of informed choice comprising knowledge, attitude and intention has gained importance. The objective of this observational study was to assess the proportion of informed choices among women invited to the German mammography screening program for the first time. A representative sample of 17,349 women aged 50 years from a sub-region of North Rhine Westphalia was invited to participate in a postal survey. Turkish immigrant women were oversampled. The effects of education level and migration status on informed choice and its components were assessed. 5,847 (33.7%) women responded to the postal questionnaire of which 4,113 were used for analyses. 31.5% of the women had sufficient knowledge. The proportion of sufficient knowledge was lower among immigrants and among women with low education levels. The proportion of women making informed choices was low (27.1%), with similar associations with education level and migration status. Women of low (OR 2.75; 95% CI 2.18-3.46) and medium education level (OR 1.49; 95% CI 1.27-1.75) were more likely to make an uninformed choice than women of high education level. Turkish immigrant women had the greatest odds for making an uninformed choice (OR 5.30, 95% CI 1.92-14.66) compared to non-immigrant women. Other immigrant women only had slightly greater odds for making an uninformed choice than non-immigrant women. As immigrant populations and women with low education level have been shown to have poor knowledge, they need special attention in measures to increase knowledge and thus informed choices.
Project description:<h4>Background</h4>Despite evidence about the "modern epidemic" of overdiagnosis, and expanding disease definitions that medicalize more people, data are lacking on public views about these issues. Our objective was to measure public perceptions about overdiagnosis and views about financial ties of panels setting disease definitions.<h4>Methods</h4>We conducted a 15 minute Computer Assisted Telephone Interview with a randomly selected community sample of 500 Australians in January 2014. We iteratively developed and piloted a questionnaire, with a convenience sample (n=20), then with participants recruited by a research company (n=20). Questions included whether respondents had been informed about overdiagnosis; opinions on informing people; and views about financial ties among panels writing disease definitions.<h4>Findings</h4>Our sample was generally representative, but included a higher proportion of females and seniors, typical of similar surveys. American Association for Public Opinion Research response rate was 20% and cooperation rate was 44%. Only 10% (95% CI 8%-13%) of people reported ever being told about overdiagnosis by a doctor. 18% (95% CI 11%-28%) of men who reported having prostate cancer screening, and 10% (95% CI 6%-15%) of women who reported having mammography said they were told about overdiagnosis. 93% (95% CI 90%-95%) agreed along with screening benefits, people should be informed about overdiagnosis. On panels setting disease definitions, 78% (95% CI 74%-82%) felt ties to pharmaceutical companies inappropriate, and 91% (95% CI 82%-100%) believed panels should have a minority or no members with ties. Limitations included questionnaire novelty and complexity.<h4>Conclusions</h4>A small minority of Australians surveyed, including those reporting being screened for prostate or breast cancer, reported being informed of overdiagnosis; most believed people should be informed; and a majority felt it inappropriate that doctors with ties to pharmaceutical companies write disease definitions. Results suggest strategies to better inform people about overdiagnosis, and review disease definition processes, have significant public sympathy.
Project description:Population breast screening has been implemented in the UK for over 25 years, but the size of benefit attributable to such programmes remains controversial. We have conducted the first individual-based cohort evaluation of population breast screening in the UK, to estimate the impact of the NHS breast screening programme (NHSBSP) on breast cancer mortality.We followed 988?090 women aged 49-64 years in 1991 resident in England and Wales, who because of the staggered implementation of the NHSBSP, included both invited subjects and an uninvited control group. Individual-level breast screening histories were linked to individual-level mortality and breast cancer incidence data from national registers. Risk of death from breast cancer was investigated by incidence-based mortality analyses in relation to intention to screen and first round attendance. Overdiagnosis of breast cancer following a single screening round was also investigated.Invitation to NHSBSP screening was associated with a reduction in breast cancer mortality in 1991-2005 of 21% (RR=0.79, 95% CI: 0.73-0.84, P<0·001) after adjustment for age, socioeconomic status and lead-time. Breast cancer deaths among first invitation attenders were 46% lower than among non-attenders (RR=0.54, 95% CI: 0.51-0·57, P<0.001) and 32% lower following adjustment for age, socioeconomic status and self-selection bias (RR=0.68, 95% CI: 0.63-0·73, P<0.001). There was little evidence of overdiagnosis associated with invitation to first screen.The results indicate a substantial, statistically significant reduction in breast cancer mortality between 1991 and 2005 associated with NHSBSP activity. This is important in public health terms.
Project description:Although screening mammography has delivered many benefits since its introduction in Canada in 1988, questions about perceived harms warrant an up-to-date review. To help oncologists and physicians provide optimal patient recommendations, the literature was reviewed to find the latest guidelines for screening mammography, including benefits and perceived harms of overdiagnosis, false positives, false negatives, and technologic advances. For women 40-74 years of age who actually participate in screening every 1-2 years, breast cancer mortality is reduced by 40%. With appropriate corrections, overdiagnosis accounts for 10% or fewer breast cancers. False positives occur in about 10% of screened women, 80% of which are resolved with additional imaging, and 10%, with breast biopsy. An important limitation of screening is the false negatives (15%-20%). The technologic advances of digital breast tomosynthesis, breast ultrasonography, and magnetic resonance imaging counter the false negatives of screening mammography, particularly in women with dense breast tissue.