Effect of population breast screening on breast cancer mortality up to 2005 in England and Wales: an individual-level cohort study.
ABSTRACT: 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:BACKGROUND:The appropriate age range for breast cancer screening remains a matter of debate. We aimed to estimate the effect of mammographic screening at ages 40-48 years on breast cancer mortality. METHODS:We did a randomised, controlled trial involving 23 breast screening units across Great Britain. We randomly assigned women aged 39-41 years, using individual randomisation, stratified by general practice, in a 1:2 ratio, to yearly mammographic screening from the year of inclusion in the trial up to and including the calendar year that they reached age 48 years (intervention group), or to standard care of no screening until the invitation to their first National Health Service Breast Screening Programme (NHSBSP) screen at approximately age 50 years (control group). Women in the intervention group were recruited by postal invitation. Women in the control group were unaware of the study. The primary endpoint was mortality from breast cancers (with breast cancer coded as the underlying cause of death) diagnosed during the intervention period, before the participant's first NHSBSP screen. To study the timing of the mortality effect, we analysed the results in different follow-up periods. Women were included in the primary comparison regardless of compliance with randomisation status (intention-to-treat analysis). This Article reports on long-term follow-up analysis. The trial is registered with the ISRCTN registry, ISRCTN24647151. FINDINGS:160?921 women were recruited between Oct 14, 1990, and Sept 24, 1997. 53?883 women (33·5%) were randomly assigned to the intervention group and 106?953 (66·5%) to the control group. Between randomisation and Feb 28, 2017, women were followed up for a median of 22·8 years (IQR 21·8-24·0). We observed a significant reduction in breast cancer mortality at 10 years of follow-up, with 83 breast cancer deaths in the intervention group versus 219 in the control group (relative rate [RR] 0·75 [95% CI 0·58-0·97]; p=0·029). No significant reduction was observed thereafter, with 126 deaths versus 255 deaths occurring after more than 10 years of follow-up (RR 0·98 [0·79-1·22]; p=0·86). INTERPRETATION:Yearly mammography before age 50 years, commencing at age 40 or 41 years, was associated with a relative reduction in breast cancer mortality, which was attenuated after 10 years, although the absolute reduction remained constant. Reducing the lower age limit for screening from 50 to 40 years could potentially reduce breast cancer mortality. FUNDING:National Institute for Health Research Health Technology Assessment programme.
Project description:In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP).In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM.We obtained 33?146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26?054 women were eligible for this analysis (12?807 in the intervention group and 13?247 in the control group). Participation within 90 days of the first offered appointment was significantly higher in the intervention group (2861 [22%] of 12?807) than in the control group (1632 [12%] of 13?247); relative risk of participation 1·81 (95% CI 1·70-1·93; p<0·0001).These findings show that a policy of second appointments with fixed date and time for non-attenders of breast screening is effective in improving participation. This strategy can be easily implemented by the screening sites and, if combined with simple interventions, could further increase participation and ensure an upward shift in the participation trend nationally. Whether the policy should vary by time since last attended screen will have to be considered.National Health Service Cancer Screening Programmes and Department of Health Policy Research Programme.
Project description:OBJECTIVES:Potentially modifiable risk factors account for approximately 23% of breast cancers, with obesity and alcohol being the two greatest. Breast screening and symptomatic clinical attendances provide opportunities ('teachable moments') to link health promotion and breast cancer-prevention advice within established clinical pathways. This study explored knowledge and attitudes towards alcohol as a risk factor for breast cancer, and potential challenges inherent in incorporating advice about alcohol health risks into breast clinics and screening appointments. DESIGN:A mixed-method study including a survey on risk factors for breast cancer and understanding of alcohol content. Survey results were explored in a series of five focus groups with women and eight semi-structured interviews with health professionals. SETTING:Women attending NHS Breast Screening Programme (NHSBSP) mammograms, symptomatic breast clinics and healthcare professionals in those settings. PARTICIPANTS:205 women were recruited (102 NHSBSP attenders and 103 symptomatic breast clinic attenders) and 33 NHS Staff. RESULTS:Alcohol was identified as a breast cancer risk factor by 40/205 (19.5%) of attenders and 16/33 (48.5%) of staff. Overall 66.5% of attenders drank alcohol, and 56.6% could not estimate correctly the alcohol content of any of four commonly consumed alcoholic drinks. All women agreed that including a prevention-focussed intervention would not reduce the likelihood of their attendance at screening mammograms or breast clinics. Qualitative data highlighted concerns in both women and staff of how to talk about alcohol and risk factors for breast cancer in a non-stigmatising way, as well as ambivalence from specialist staff as to their role in health promotion. CONCLUSIONS:Levels of alcohol health literacy and numeracy were low. Adding prevention interventions to screening and/or?symptomatic clinics appears acceptable to attendees, highlighting the potential for using these opportunities as 'teachable moments'. However, there are substantial cultural and systemic challenges to overcome if this is to be implemented successfully.
Project description:BACKGROUND: Trend studies investigating the impact of mammographic screening usually display age-specific mortality and incidence rates over time, resulting in an underestimate of the benefit of screening, that is, mortality reduction, and an overestimate of its major harmful effect, that is, overdiagnosis. This study proposes a more appropriate way of analysing trends. METHODS: Breast cancer mortality (1950-2009) and incidence data (1975-2009) were obtained from Statistics Netherlands, 'Stg. Medische registratie' and the National Cancer Registry in the Netherlands for women aged 25-85 years. Data were visualised in age-birth cohort and age-period figures. RESULTS: Birth cohorts invited to participate in the mammographic screening programme showed a deflection in the breast cancer mortality rates within the first 5 years after invitation. Thereafter, the mortality rate increased, although less rapidly than in uninvited birth cohorts. Furthermore, invited birth cohorts showed a sharp increase in invasive breast cancer incidence rate during the first 5 years of invitation, followed by a moderate increase during the following screening years and a decline after passing the upper age limit. CONCLUSION: When applying a trend study to estimate the impact of mammographic screening, we recommend using a birth cohort approach.
Project description:To explore the influence of overdiagnosis information on women's decisions about mammography.A qualitative focus group study with purposive sampling and thematic analysis, in which overdiagnosis information was presented.Community and university settings in London.40 women within the breast screening age range (50-71 years) including attenders and non-attenders were recruited using a recruitment agency as well as convenience sampling methods.Women expressed surprise at the possible extent of overdiagnosis and recognised the information as important, although many struggled to interpret the numerical data. Overdiagnosis was viewed as less-personally relevant than the possibility of 'under diagnosis' (false negatives), and often considered to be an issue for follow-up care decisions rather than screening participation. Women also expressed concern that information on overdiagnosis could deter others from attending screening, although they rarely saw it as a deterrent. After discussing overdiagnosis, few women felt that they would make different decisions about breast screening in the future.Women regard it as important to be informed about overdiagnosis to get a complete picture of the risks and benefits of mammography, but the results of this study indicate that understanding overdiagnosis may not always influence women's attitudes towards participation in breast screening. The results also highlight the challenge of communicating the individual significance of information derived from population-level modelling.
Project description:Background The purpose of mammography screening is to decrease breast cancer mortality. To achieve this a high coverage by examination is needed. Within an organized screening programme, we examined the impact of changes in the invitation schedule on the interplay between coverage and participation. Method We studied nine cohorts aged 50-51 when first targeted by mammography screening in Copenhagen, Denmark. Population data were retrieved from the Danish Civil Registration System; invitation and attendance data from the screening programme database. Data were linked using unique personal identification numbers. Coverage by invitation was defined as (number of invited women/number of targeted women), coverage by examination as (number of screened women/number of targeted women), and participation rate as (number of screened women/number of invited women). Results Coverage by invitation was close to or above 95% for all newly recruited cohorts. In subsequent invitation rounds, both technical errors and changes in the invitation scheme affected the coverage by invitation. Coverage by examination at first invitation was 72.5% for the first cohort, but dropped to 64.2% for the latest cohort. Furthermore, coverage by examination dropped by increasing invitation number and with omission of re-invitation of previous non-attenders. Participation rate closely reflected changes in the invitation scheme. Conclusion Changes in the invitation schemes influenced coverage by invitation, coverage by examination, and participation rate. We observed a considerable gap between coverage by examination and participation rate, strongly indicating that the latter cannot without reservations, be taken as an indicator of the first.
Project description:<h4>Objective</h4>To use data from two longstanding, population based screening programmes to study overdiagnosis in screening mammography.<h4>Design</h4>Population based cohort study.<h4>Setting</h4>Copenhagen municipality (from 1991) and Funen County (from 1993), Denmark.<h4>Participants</h4>57,763 women targeted by organised screening, aged 56-69 when the screening programmes started, and followed up to 2009.<h4>Main outcome measures</h4>Overdiagnosis of breast cancer in women targeted by screening, assessed by relative risks compared with historical control groups from screening regions, national control groups from non-screening regions, and historical national control groups.<h4>Results</h4>In total, 3279 invasive breast carcinomas and ductal carcinomas in situ occurred. The start of screening led to prevalence peaks in breast cancer incidence: relative risk 2.06 (95% confidence interval 1.64 to 2.59) for Copenhagen and 1.84 (1.46 to 2.32) for Funen. During subsequent screening rounds, relative risks were slightly above unity: 1.04 (0.85 to 1.27) for Copenhagen and 1.14 (0.98 to 1.32) for Funen. A compensatory dip was seen after the end of invitation to screening: relative risk 0.80 (0.65 to 0.98) for Copenhagen and 0.67 (0.55 to 0.81) for Funen during the first four years. The relative risk of breast cancer accumulated over the entire follow-up period was 1.06 (0.90 to 1.25) for Copenhagen and 1.01 (0.93 to 1.10) for Funen. Relative risks for participants corrected for selection bias were estimated to be 1.08 for Copenhagen and 1.02 for Funen; for participants followed for at least eight years after the end of screening, they were 1.05 and 1.01. A pooled estimate gave 1.040 (0.99 to 1.09) for all targeted women and 1.023 (0.97 to 1.08) for targeted women followed for at least eight years after the end of screening.<h4>Conclusions</h4>On the basis of combined data from the two screening programmes, this study indicated that overdiagnosis most likely amounted to 2.3% (95% confidence interval -3% to 8%) in targeted women. Among participants, it was most likely 1-5%. At least eight years after the end of screening were needed to compensate for the excess incidence during screening.
Project description:BACKGROUND:The role of breast screening in breast cancer mortality declines is debated. Screening impacts cancer mortality through decreasing the number of advanced cancers with poor diagnosis, while cancer treatment works through decreasing the case-fatality rate. Hence, reductions in cancer death rates thanks to screening should directly reflect reductions in advanced cancer rates. We verified whether in breast screening trials, the observed reductions in the risk of breast cancer death could be predicted from reductions of advanced breast cancer rates. PATIENTS AND METHODS:The Greater New York Health Insurance Plan trial (HIP) is the only breast screening trial that reported stage-specific cancer fatality for the screening and for the control group separately. The Swedish Two-County trial (TCT)) reported size-specific fatalities for cancer patients in both screening and control groups. We computed predicted numbers of breast cancer deaths, from which we calculated predicted relative risks (RR) and (95% confidence intervals). The Age trial in England performed its own calculations of predicted relative risk. RESULTS:The observed and predicted RR of breast cancer death were 0.72 (0.56-0.94) and 0.98 (0.77-1.24) in the HIP trial, and 0.79 (0.78-1.01) and 0.90 (0.80-1.01) in the Age trial. In the TCT, the observed RR was 0.73 (0.62-0.87), while the predicted RR was 0.89 (0.75-1.05) if overdiagnosis was assumed to be negligible and 0.83 (0.70-0.97) if extra cancers were excluded. CONCLUSIONS:In breast screening trials, factors other than screening have contributed to reductions in the risk of breast cancer death most probably by reducing the fatality of advanced cancers in screening groups. These factors were the better management of breast cancer patients and the underreporting of breast cancer as the underlying cause of death. Breast screening trials should publish stage-specific fatalities observed in each group.
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:Background:Biennial screening is generally recommended for average-risk women aged 50 to 74 years, but tailored screening may provide greater benefits. Objective:To estimate outcomes for various screening intervals after age 50 years based on breast density and risk for breast cancer. Design:Collaborative simulation modeling using national incidence, breast density, and screening performance data. Setting:United States. Patients:Women aged 50 years or older with various combinations of breast density and relative risk (RR) of 1.0, 1.3, 2.0, or 4.0. Intervention:Annual, biennial, or triennial digital mammography screening from ages 50 to 74 years (vs. no screening) and ages 65 to 74 years (vs. biennial digital mammography from ages 50 to 64 years). Measurements:Lifetime breast cancer deaths, life expectancy and quality-adjusted life-years (QALYs), false-positive mammograms, benign biopsy results, overdiagnosis, cost-effectiveness, and ratio of false-positive results to breast cancer deaths averted. Results:Screening benefits and overdiagnosis increase with breast density and RR. False-positive mammograms and benign results on biopsy decrease with increasing risk. Among women with fatty breasts or scattered fibroglandular density and an RR of 1.0 or 1.3, breast cancer deaths averted were similar for triennial versus biennial screening for both age groups (50 to 74 years, median of 3.4 to 5.1 vs. 4.1 to 6.5 deaths averted; 65 to 74 years, median of 1.5 to 2.1 vs. 1.8 to 2.6 deaths averted). Breast cancer deaths averted increased with annual versus biennial screening for women aged 50 to 74 years at all levels of breast density and an RR of 4.0, and those aged 65 to 74 years with heterogeneously or extremely dense breasts and an RR of 4.0. However, harms were almost 2-fold higher. Triennial screening for the average-risk subgroup and annual screening for the highest-risk subgroup cost less than $100 000 per QALY gained. Limitation:Models did not consider women younger than 50 years, those with an RR less than 1, or other imaging methods. Conclusion:Average-risk women with low breast density undergoing triennial screening and higher-risk women with high breast density receiving annual screening will maintain a similar or better balance of benefits and harms than average-risk women receiving biennial screening. Primary Funding Source:National Cancer Institute.