***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Summary In March 1981 , 40,318 women in Stockholm , aged 40–64 , entered a r and omized trial of breast cancer screening by single-view mammography alone versus no intervention in a control group of 20,000 women . The attendance rate during the first screening round was 81 per cent and the cancer detection rate was 4.0 per 1000 women . The detection the rate fell to 3.1 per 1000 in the second round , which was completed in October 1985 . During 1986 the controlled design of the study was broken and the contro women were invited once to screening which was completed the same year . A total of 428 cases of breast cancer were thus diagnosed in the study group and 439 in the adjusted control group . After a mean follow-up of 7.4 years the number of breast cancer deaths in the study and control groups was 39 and 30 respectively . The relative risk of breast cancer death ( screening versus control ) was 0.71 ( 95 per cent confidence interval : 0.4–1.2 ) . Among women older than 50 years at entry the relative risk was 0.57 ( 95 per cent confidence interval : 0.3–1.1 ) . Cancer deaths among women under 50 were few and perhaps because of this no mortality reduction was seen in this age group . The estimate of mortality reduction lies between the results from two earlier Swedish r and omized controlled trials Results from the r and omized trial conducted by the Health Insurance Plan ( HIP ) to determine the efficacy of breast cancer screening with mammography and palpation are reported for longer periods than previously available . By the end of 10 years after entry , the study group 's  mortality due to breast cancer was about 30 % below the control group 's . Arithmetic gains due to screening were maintained through year 14 ; relative gains declined . With increases in the period of follow-up , cumulative survival rates among cases detected by mammography alone ( palpation negative during screening ) , decreased more rapidly than rates among other subgroups , but survival rates for mammography cases remained relatively high . Study women aged 40 - 49 years at entry began to show lower breast cancer mortality than those in the control group as duration of follow-up increased . Reservations are advanced about the acceptance of this finding as evidence of the efficacy of screening under age 50 under the conditions of the HIP study . The reservations are based on the observation that the decrease of mortality among the study group aged 45 - 49 at entry is concentrated entirely among cases diagnosed after they reached 50 years of age BACKGROUND The Swedish Two-County Trial has been criticised on the grounds of the cluster r and omisation and alleged bias in classification of cause of death . PATIENTS AND METHODS In the Two-County Trial , 77 080 women were r and omised to regular invitation to screening ( active study population , ASP ) and 55 985 to no invitation ( passive study population , PSP ) , in 45 geographical clusters . After approximately 7 years , the PSP was invited to screening and the trial closed . We analysed data using hierarchical statistical models to take account of cluster r and omisation , and performed a conservative analysis assuming a systematic difference between ASP and PSP in baseline breast cancer mortality in one of the counties . We also analysed deaths from causes other than breast cancer and from all causes among breast cancer cases diagnosed in the ASP and PSP . RESULTS Taking account of the cluster r and omisation there was a significant 30 % reduction in breast cancer mortality in the ASP . Conservatively , assuming a systematic difference between ASP and PSP clusters in baseline breast cancer mortality , there was a significant 27 % reduction in mortality in the ASP . Ignoring classification of cause of death , there was a significant 13 % reduction in all-cause mortality in breast cancer cases in the ASP . CONCLUSIONS Breast cancer mortality is a valid end point and mammographic screening does indeed reduce mortality from breast cancer . The criticisms of the Swedish Two-County Trial are unfounded Debate continues over the effectiveness of screening by mammography in women below age 50 . We report here on results of screening in the first 10 years of a r and omised trial to study the effect on breast cancer mortality of  invitation to annual mammography  from age 40 to 41 compared to first invitation to the 3-yearly  UK national programme  at age 50–52 . The trial is taking place in 23 NHS breast screening centres . Between 1991 and 1997 , 160 921 women were r and omised in the ratio 1 : 2 to intervention and control arms . Screening is by two views at first screen and single view subsequently ; data on screening up to and including round five are now complete . Uptake of invitation to screening is between 68 and 70 % at all but the latest screening rounds . Rates of referral for assessment are 4.6 % at first screen and 3.4 % at subsequent screens . Invasive cancer detection rates are 0.09 % at first screen , and similar at rescreens until the sixth and later screens . There is little evidence of regular mammography in the trial control arm . The setting of this trial within the NHS breast screening programme should ensure applicability of results to a national programme OBJECTIVES To evaluate the efficacy of the combination of annual screening with mammography , physical examination of the breasts and the teaching of breast self-examination in reducing the rate of death from breast cancer among women aged 40 to 49 years on entry . DESIGN Individually r and omized controlled trial . SETTING Fifteen urban centres in Canada with expertise in the diagnosis and treatment of breast cancer . PARTICIPANTS Women with no history of breast cancer and no mammography in the previous 12 months were r and omly assigned to undergo either  annual mammography and physical examination ( MP group ) or usual care after an initial physical examination ( UC group ) . The 50,430 women enrolled from January 1980 through March 1985 were followed for a mean of 8.5 years . DATA COLLECTION Derived from the participants by initial and annual self-administered question naires , from the screening examinations , from the patients ' physicians , from the provincial cancer registries and by record linkage to the Canadian National Mortality Data Base . Expert panels evaluated histologic and death data . MAIN OUTCOME MEASURES Rates of referral from screening , rates of detection of breast cancer from screening and from community care , nodal status , tumour size , and rates of death from all causes and from breast cancer . RESULTS Over 90 % of the women in each group attended the screening sessions or returned the annual question naires , or both , over years 2 to 5 . The characteristics of the women in the two groups were similar . Compared with the Canadian population , the participants were more likely to be married , have fewer children , have more education , be in a professional occupation , smoke less and have been born in North America . The rate of screen-detected breast cancer on first examination was 3.89 per 1000 in the MP group and 2.46 per 1000 in the UC group ; more node-positive tumours were found in the MP group than in the UC group . During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.26 in the MP group and 1.02 in the UC group . Of the women with invasive breast cancer through to 7 years , 191 and 157 women in the MP and UC groups respectively had no node involvement , 55 and 43 had one to three nodes involved , 47 and 23 had four or more nodes involved , and 38 and 49 had an unknown nodal status . There were 38 deaths from breast cancer in the MP group and 28 in the UC group . The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 1.36 ( 95 % confidence interval 0.84 to 2.21 ) . The survival rates were similar in the two groups . The highest survival rate occurred among women whose cancer had been detected by mammography alone . CONCLUSION The study was internally valid , and there was no evidence of r and omization bias . Screening with yearly mammography and physical examination of the breasts detected considerably more node-negative , small tumours than usual care , but it had no impact on the rate of death from breast cancer up to 7 years ' follow-up from entry BACKGROUND Age-specific effects of mammographic screening , and the timing of such effects , are a matter of debate . The results of the UK Age trial , which compared the effect of invitation to annual mammographic screening from age 40 years with commencement of screening at age 50 years on breast cancer mortality , have been reported at 10 years of follow-up and showed no significant difference in mortality between the trial groups . Here , we report the results of the UK Age trial after 17 years of follow-up . METHODS Women aged 39 - 41 from 23 UK NHS Breast Screening Programme units years were r and omly assigned by individual r and omisation ( 1:2 ) to either an intervention group offered annual screening by mammography up to and including the calendar year of their 48th birthday or to a control group receiving usual medical care ( invited for screening at age 50 years and every 3 years thereafter ) . Both groups were stratified by general practice . We compared breast cancer incidence and mortality by time since r and omisation . Analyses included all women r and omly assigned who could be traced with the National Health Service Central Register and who had not died or emigrated before entry . The primary outcome measures were mortality from breast cancer ( defined as deaths with breast cancer coded as the underlying cause of death ) and breast cancer incidence , including in-situ , invasive , and total incidence . Because there is an interest in the timing of the mortality effect , we analysed the results in different follow-up periods . This trial is registered , number IS RCT N24647151 . FINDINGS Between Oct 14 , 1990 , and Sept 25 , 1997 , 160 921 participants were r and omly assigned ; 53 883 women in the intervention group and 106 953 assigned to usual medical care were included in this analysis . After a median follow-up of 17 years ( IQR 16·8 - 18·8 ) , the rate ratio ( RR ) for breast cancer mortality was 0·88 ( 95 % CI 0·74 - 1·04 ) from tumours diagnosed during the intervention phase . A significant reduction in breast cancer mortality was noted in the intervention group compared with the control group in the first 10 years after diagnosis ( RR 0·75 , 0·58 - 0·97 ) but not thereafter ( RR 1·02 , 0·80 - 1·30 ) from tumours diagnosed during the intervention phase . The overall breast cancer incidence during 17 year follow-up was similar between the intervention group and the control group ( RR 0·98 , 0·93 - 1·04 ) . INTERPRETATION Our results support an early reduction in mortality from breast cancer with annual mammography screening in women aged 40 - 49 years . Further data are needed to fully underst and long-term effects . Cumulative incidence figures suggest at worst a small amount of overdiagnosis . FUNDING National Institute for Health Research Health Technology Assessment programme and the American Cancer Society . Past funding was received from the Medical Research Council , Cancer Research UK , the UK Department of Health , and the US National Cancer Institute Objective To compare breast cancer incidence and mortality up to 25 years in women aged 40 - 59 who did or did not undergo mammography screening .  Design Follow-up of r and omised screening trial by centre coordinators , the study ’s central office , and linkage to cancer registries and vital statistics data bases . Setting 15 screening centres in six Canadian provinces,1980 - 85 ( Nova Scotia , Quebec , Ontario , Manitoba , Alberta , and British Columbia ) . Participants 89 835 women , aged 40 - 59 , r and omly assigned to mammography  ( five annual mammography screens ) or control ( no mammography ) . Interventions Women aged 40 - 49 in the mammography arm and all women aged 50 - 59 in both arms received annual physical breast examinations . Women aged 40 - 49 in the control arm received a single examination followed by usual care in the community . Main outcome measure Deaths from breast cancer . Results During the five year screening period , 666 invasive breast cancers were diagnosed in the  mammography arm ( n=44 925 participants ) and 524 in the controls ( n=44 910 ) , and of these , 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period . The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 ( 95 % confidence interval 0.85 to 1.30 ) . The findings for women aged 40 - 49 and 50 - 59 were almost identical . During the entire study period , 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer , and 500 and 505 , respectively , died of breast cancer . Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm ( hazard ratio 0.99 , 95 % confidence interval 0.88 to 1.12 ) . After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm , attributable to over-diagnosis . Conclusion Annual mammography in women aged 40 - 59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available . Overall , 22 % ( 106/484 ) of screen detected invasive 
    Output:
    
Studies providing outcomes specific to age , risk factors , screening intervals , and modalities were preferred over studies providing general outcomes , when available .
Studies most clinical ly relevant to practice in the United States were selected over studies that were less relevant .