Annual mammographic screening to reduce breast cancer mortality in women from age 40 years: long-term follow-up of the UK Age RCT (original) (raw)
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The Lancet, 2006
Background The effi cacy of screening by mammography has been shown in randomised controlled trials in women aged 50 years and older, but is less clear in younger women. A meta-analysis of all previous trials showed a 15% mortality reduction in invited women aged 40-49 years at study entry, but this fi nding could be due in part to screening of women after age 50 years. The Age trial was designed to study the eff ect on mortality of inviting women for annual mammography from age 40 years. Methods 160 921 women aged 39-41 years were randomly assigned in the ratio 1:2 to an intervention group of annual mammography to age 48 years or to a control group of usual medical care. The trial was undertaken in 23 NHS breast-screening units in England, Wales, and Scotland. The primary analysis was based on the intention-to-treat principle and compared mortality rates in the two groups at 10 years' follow-up. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN24647151. Findings At a mean follow-up of 10•7 years there was a reduction in breast-cancer mortality in the intervention group, in relative and absolute terms, which did not reach statistical signifi cance (relative risk 0•83 [95% CI 0•66-1•04], p=0•11; absolute risk reduction 0•40 per 1000 women invited to screening [95% CI-0•07 to 0•87]). Mortality reduction adjusted for non-compliance in women actually screened was estimated as 24% (RR 0•76, 95% CI 0•51-1•01). Interpretation Although the reduction in breast-cancer mortality observed in this trial is not signifi cant, it is consistent with results of other trials of mammography alone in this age-group. Future decisions on screening policy should be informed by further follow-up from this trial and should take account of possible costs and harms as well as benefi ts.
BMJ, 2000
Objective To assess the impact of the NHS breast screening programme on mortality from breast cancer in women aged 55-69 years over the period 1990-8. Design Age cohort model with data for 1971-89 used to predict mortality for 1990-8 with assumption of no major effect from screening or improvements in treatment until after 1989. Effect of screening and other factors on mortality estimated by comparing three year moving averages of observed mortality with those predicted (by five year age groups from 50-54 to 75-79), the effect of screening being restricted to certain age groups. Setting England and Wales. Subjects Women aged 40 to 79 years. Results Compared with predicted mortality in the absence of screening or other effects the total reduction in mortality from breast cancer in 1998 in women aged 55-69 was estimated as 21.3%. Direct effect of screening was estimated as 6.4% (range of estimates from 5.4-11.8%). Effect of all other factors (improved treatment with tamoxifen and chemotherapy, and earlier presentation outside the screening programme) was estimated as 14.9% (range 12.2-14.9%). Conclusions By 1998 both screening and other factors, including improvements in treatment, had resulted in substantial reductions in mortality from breast cancer. Many deaths in the 1990s will be of women diagnosed in the 1980s and early 1990s, before invitation to screening. Further major effects from screening and treatment are expected, which together with cohort effects should result in further substantial reductions in mortality from breast cancer, particularly for women aged 55-69, over the next 10 years.
2010
Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50-69 years. Setting The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50-69 years. Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974-2004 and 1974-2003, respectively). We used Poisson regression for statistical inference. Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial (P , 0.001) and the screening programme in England (P , 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.
Repeated mammographic screening reduces breast cancer mortality along the continuum of age
Journal of Medical Screening, 2002
Objective: The optimal age boundaries for breast cancer screening are still under debate. A case-referent design was used to describe the effect of mammographic screening on breast cancer mortality along the continuum of age, based on a 20 year follow up period. Setting: The population based breast cancer screening programme in Nijmegen, The Netherlands, which has biennially invited women over 35 years since 1975. Methods: Cases, defined as women who died from primary breast cancer between 1987 and 1997, were selected from the group of women who received at least one invitation to the screening programme. For 157 cases, 785 women from the same group were selected as referents. Information on the index screening (the screening examination preceding diagnosis of the case) was collected for both cases and referents. The risk of dying from breast cancer was calculated per 10 year moving age group for women who had attended the index screening versus those who had not. Results: The youngest 10 year age group showing an effect in our study were women aged 45-54 at their index screening. Breast cancer mortality for women in this group who attended the index screening was 32% lower, although not significant, than for women who did not (odds ratio (OR) 0.68, 95% confidence interval (95% CI) 0.33 to 1.41). This reduction in risk was not explained solely by an effect in women over 50 because the OR in women aged 45-49 was 0.56 (95% CI 0.20 to 1.61). Reductions in mortality became smaller with increasing age. Nevertheless, for women over 60 at index screening, participation in screening over a maximum 4 year period before diagnosis of the case yielded protective effects at least up to an age around 80. Conclusions: Although our results are based on a relatively small number of cases, they suggest that even in a programme with a 2 year screening interval there may be a benefit of starting screening around age 45. Also older women who participate at least once every 4 years still have much to gain from screening. I n screening for breast cancer, among the issues still under debate are the optimal lower and upper age boundaries delineating the target population. 1-3 In younger women breast cancer is a relatively important cause of death, but the effect of mammographic screening is not clear cut. A National Institute of Health consensus development conference in 1997, focusing on women of 40-49, did not produce a unanimous statement on when to start mammographic screening. 4 Since then a new meta-analysis including the most recent follow up data on all eight randomised controlled trials showed for the first time a significant 18% reduction in mortality among women of 40-49 at entry into the trials. 5 Also accumulating evidence shows that mammographic screening in younger women meets levels of performance compared with performance in women 50 years and older, especially if programmes achieve high quality and screen at 12-18 month intervals. The impact of (continuing) screening by mammography at older ages has been studied to a lesser extent, but is likely to receive considerable attention in the next decade with a growing population of healthy elderly women. 2 6 To our knowledge, only three studies reported on the effect of screening women over 65. All indicated that the reduction in breast cancer mortality among women of 65-74 may be as large as 55%. 7-9 A model based study further reported that even under pessimistic assumptions, the balance between positive and negative effects of breast cancer screening remains favourable up to an age around 80. Commonly used cut off points for age specific effects of mammographic screening in previously published reports are arbitrary to some extent and have no direct biological justification. Therefore, one of the suggestions for future research of the National Institute of Health Consensus Development Panel was to examine the effects of mammography screening for all ages at risk, looking upon age as a continuum. 4 As shown by Smith, 3 comparing breast cancer screening among successive-for example, 10 year-age groups is also more relevant to public health policy because of the gradual increasing trend in the efficacy of screening as women age. In the population based programme in Nijmegen, introduced in 1975, screening was offered to women aged 35 and older over a 20 year period. This setting provides an opportunity to study the effect of attending screening over the whole age range of women invited.
British Journal of Cancer, 2016
Background: The usefulness of case-control studies has been questioned. Our aim was to evaluate the long-term effect of screening on breast cancer mortality within the population-based mammography programme in Finland using a case-control design, and to compare the analyses with the earlier cohort study. Methods: The cases were women invited to screening, diagnosed and died from breast cancer in 1992-2011 while being 50-84 years at death. We chose 10 controls for each case with non-restrictive eligibility criteria. Our data included 1907 cases and 18 978 matched controls. We analysed associations between the screening participation and the risk of breast cancer death using the conditional Cox proportional hazards model. The effect estimates were corrected for self-selection bias. Results: An overall effect of screening was 0.67 (95% confidence interval (CI): 0.49-0.90), and that remained unchanged over time. Analyses with matching criteria comparable to the cohort study yielded an effect (0.70, 95% CI: 0.49-1.00) in 1992-2003 similar to that of the previous cohort analysis (0.72, 95% CI: 0.56-0.88). Conclusions: Organised mammography screening decreases mortality from breast cancer by 33% among the participants. If made comparable, a case-cohort study can yield effect estimates similar to a cohort study.
JNCI Monographs
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.
Model of outcomes of screening mammography: information to support informed choices
BMJ, 2005
Objective To provide easy to use estimates of the benefits and harms of biennial screening mammography for women aged 40, 50, 60, and 70 years. Design Markov process model, with data from BreastScreen Australia, the Australian Institute of Health and Welfare, and the Australian Bureau of Statistics. Main outcome measure Age specific outcomes expressed per 1000 women over 10 years. Results For every 1000 women screened over 10 years, 167-251 (depending on age) receive an abnormal result; 56-64 of these women undergo at least one biopsy, 9-26 have an invasive cancer detected by screening, and 3-6 have ductal carcinoma in situ (DCIS) detected by screening. More breast cancers (both invasive and DCIS) are diagnosed among screened than unscreened women. For example, among 1000 women aged 50 who have five biennial screens, 33 breast cancers are diagnosed: 28 invasive cancers (18 detected at screening and 10 interval cancers) and five DCIS (all detected at screening). By comparison, among 1000 women aged 50 who decline screening, 20 cancers are diagnosed over 10 years. There are about 0.5, 2, 3, and 2 fewer deaths from breast cancer over 10 years per 1000 women aged 40, 50, 60, and 70, respectively, who choose to be screened compared with women who decline screening at times determined by relevant policy. Conclusion Benefits and harms of screening mammography are relatively finely balanced. Quantitative estimates such as these can be used to support individual informed choices about screening.
Impact of Screening on Breast Cancer Mortality: The UK Program 20 Years On
Cancer Epidemiology, Biomarkers & Prevention, 2015
Background: With changes in diagnosis, treatment, and management of breast cancer since the mammography screening trials, there is a need to evaluate contemporary breast screening programs. A case–control study was set up to assess the current impact of attendance in the English Breast Screening Program on breast cancer mortality. Methods: Cancer registry cases who died from primary breast cancer ages 47 to 89 years in London in 2008 to 2009 (869 women) were matched to 1 or 2 general population controls (1,642 women) with no diagnosis of breast cancer at the time of the case's diagnosis, who were alive at the case's death. Cases and controls were matched for date of birth and screening area, and had been invited to breast screening at least once prior to the case's diagnosis. ORs were estimated using conditional logistic regression. Self-selection bias was addressed using contemporaneous attendance at the cervical screening program. Sensitivity analyses were undertaken t...