***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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    ***EXAMPLES*** 
    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 A cross-sectional , r and omized screening with mammary radiography of 15 748 women aged 45 to 69 and living in Malmö for the detection of breast carcinoma is described . The detection rate of breast carcinoma was 7.5 per 1 000 , 16 per cent of the carcinoma being non-invasive and 43 invasive with a diameter of at most 10 mm . The overall rate of axillary metastases was 18 per cent . The sensitivity of the  radiography  was 91.5 per cent , the specificity 99.2 per cent and the predictive value 47 per cent . It is concluded that mammary radiography is an effective screening method for detecting early carcinoma The Canadian National Breast Screening Study ( NBSS ) is a r and omized controlled trial to assess the effect of screening on breast cancer mortality . The NBSS design ated a single reference radiologist who blindly review ed over the course of the study 5200 r and omly selected two-view mammographic examinations of women not known to have breast cancer . He also review ed 575 screening-detected breast cancer ( SBC ) cases and 102 interval breast cancer ( IBC ) cases . All cancers were histologically proven . As a result of the review s , comments on inter-observer agreement , interpretation , and technical quality were conveyed on an ongoing basis to radiologists appointed to 15 NBSS screening centers .  Agreement of the reference radiologist with center radiologists was better for breast cancer cases ( kappa = 0.511 , P less than .002 ) than for those not known to have breast cancer ( kappa = 0.307 , P less than .002 ) . Observer error and technical problems led to delayed detection in 22 % of SBCs and 35 % of IBCs . Another 11 % of SBCs and 58 % of IBCs were probably mammographically occult . No similarly comprehensive review of mammography during a screening program has been published . Suggestions arising from the NBSS review were sometimes resisted by center radiologists . Measures are suggested which might facilitate acceptance of recommendations arising from audit mechanisms in mammography screening programs , thereby enhancing opportunities for mammographic excellence Characteristics of women aged 40 - 59 , recorded at an initial breast screen , were compared with the outcome of incident , invasive breast cancer occurring up to 3 years after the initial screen . The study design was case-control , nested within the study population of the Canadian National Breast Screening Study .  Screening consisted of a two-view mammographic examination and physical examination of the breasts ; additional risk factor information was obtained from self-administered question naires . Of the etiological risk factors considered only age at entry or years menstruating were significant risk factors for breast cancer ( P < 0.0025 ) . Years menstruating accounted for much of the age effect and all of the menopausal status effect . Risk factors obtainable from mammography and physical examination were more significant than self-reported risk factors , other than age or years menstruating . In spite of possible misclassification of the variable parenchymal pattern , women with a mammographic film classified as either P2 or DY had a 2-fold risk of breast cancer ( odds ratio = 2.1 ; 95 % confidence interval = 1.5 - 2.9 , P = 2.9E-05 ) . An abnormality reported by either the radiologist [ odds ratio = 1.7 ( 1.3 - 2.3 ) ] or nurse examiner [ odds ratio = 1.9 ( 1.4 - 2.6 ) ] was also associated with an independent significant risk OBJECTIVES : To estimate women 's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers . DESIGN : Cross sectional survey ( by telephone ) . SETTING : Australia ; population -based survey conducted in April 1996 . PARTICIPANTS : R and om sample of women aged 30 - 69 years . A total of 2935 women completed the Breast Health Survey ( adjusted response rate 65 % ) . A r and om sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers . RESULTS : About one third of women ( 32.2 % , 95 % CI 23.7 , 40.7 ) had an unrealistically high expectation of the sensitivity of screening mammography  , reporting it to be 95 % or higher . Approximately 40 % of the women ( 43.5 % , 95 % CI 34.4 , 52.6 ) thought that screening mammography should pick up all cancers ( should have a sensitivity of 100 % ) . Just under half the women ( 45.2 % , 95 % CI 36.1 , 54.3 ) said financial compensation should be awarded for a cancer missed by screening mammography  even if the cancer was missed as a consequence of the small failure rate of the test . Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation . CONCLUSION : Unrealistically high expectations of the sensitivity of screening mammography  were common in this group of women . Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test . Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce cl aims for financial compensation when cancers are missed 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 A trial in the UK to study the effect on mortality from breast cancer of invitation for annual mammography from the age of 40–41 , has r and omised a total of 160 921 women in the ratio 1 : 2 to the intervention and control arms . All breast cancers diagnosed in the two arms have been identified , and the histology review ed . This paper presents the results of an interim analysis using surrogate outcome measures to compare predicted breast cancer mortality in the two arms based on 1287 cases diagnosed to 31.12.1999 . Due to earlier diagnosis , there is currently an 8 % excess of invasive breast cancers in the intervention arm . The ratio of predicted deaths at 10 years in the intervention arm relative to the control arm , adjusted for this excess diagnosis , ranges from 0.89 ( 95 % confidence interval ( CI ) 0.78–1.01 ) to 0.90 ( 95 % CI 0.80–1.01 ) . Screening from age 40 may result in a lower reduction in breast cancer mortality than that observed in other trials including women below age 50 . This analysis based on surrogate outcome measures suggests that a reduction in breast cancer mortality may be observed in this trial . However , a number of assumptions have been necessary and firm conclusions must await the analysis of observed mortality from breast cancer The Canadian National Breast Screening Study ( CNBSS ) , conducted on women age 40 - 49 , was design ed to evaluate the efficacy of combined annual mammography and physical examination of the breasts in reducing breast cancer mortality in comparison to usual care ( UC ) controls . From January 1980 through March 1985 , 25,214 women were individually r and omized to the mammography/physical exam ( MP ) arm and 25,216 to the UC .  The integrity of the r and omization has been review ed and confirmed to be unbiased . During an average , follow-up of 10.5 years from entry ( range : 8.75 - 13 years ) , 82 women died from breast cancer in the MP arm and 72 in the UC , for a rate ratio of 1.14 ( 95 % confidence interval : 0.83 - 1.56 ) . All-cause mortality was almost identical comparing the two groups ; the nonsignificant excess of breast cancer deaths in the MP arm was balanced by an excess of other cancer deaths in the UC arm Large-scale public health trials are often r and omized by geographic or administrative clusters , for reasons of financial or organizational exigency . In this paper , we deal with the situation where the dependent variable is a count of events , such as mortality from , or incidence of a given disease . Simulation results show that this design may decrease power by more than 50 per cent . The lost power can largely be replaced by incorporating information on the dependent variable , within clusters , before the start of the trial . The pretrial and trial data can be analysed by negative trinomial models Eighteen months after the 1980 initiation of the Canadian National Breast Screening Study ( NBSS ) ( a multicenter r and omized controlled trial that will involve 90,000 women ) , the Toronto center experience such severe problems with recruitment that the study as a whole was jeopardized . Impediments to recruitment arose in five areas . The design of the protocol was criticized by some physicians and participants , a problem that could only be met by justifying the design . A second problem was a lack of underst and ing of the concept of screening and mistaken assumptions about what participation in the NBSS entailed . Thirdly , recruitment problems occurred at a time when the media were focusing much attention on the hazards of low-level ionizing radiation . Fourthly , women were found to have a variety of personal reasons for delaying or avoiding entry into the study . Finally , factors characteristic of the Canadian milieu such as universal health coverage may have acted as a disincentive to entry . To improve physician underst and ing , NBSS personnel made presentations at medical rounds and scientific meetings ; articles were written for medical journals . To win support from the lay public , talks were given to recreation or work-based groups . Appearances on radio and television talk shows were sought out . Mass mailings to university staff and professional associations did not produce large responses , nor did advertisements on television , radio , or in newspapers . The distribution of a check insert in a government mailing gave rise to hundreds of appointments across Canada . However , for generating an ongoing adequate level of recruitment , the best measure has been the mailing of personally addressed letters to eligible women followed by a telephone call . Data on response rates , cost and women 's attitudes toward the study are reported . By early 1983 , Toronto met its recruitment target of 12,000 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 
    Output:
    
We found that breast cancer mortality was an unreliable outcome that was biased in favour of screening , mainly because of differential misclassification of cause of death .
Because of substantial advances in treatment and greater breast cancer awareness since the trials were carried out , it is likely that the absolute effect of screening today is smaller than in the trials .
Recent observational studies show more overdiagnosis than in the trials and very little or no reduction in the incidence of advanced cancers with screening