title: Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration Randomised controlled trial of mammographic screening in women from age 40: predicted mortality based on surrogate outcome measures Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Digital Mammography: Evaluation in a Population-based Screening Program. Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2): a population-based prospective study. Interval breast cancers in the 'screening with tomosynthesis or standard mammography' (STORM) population-based trial. Application of breast tomosynthesis in screening: incremental effect on mammography acquisition and reading time. Breast screening using 2D-mammography or integrating digital breast tomosynthesis (3D-mammography) for single-reading or double-reading--evidence to guide future screening strategies. Performance of one-view breast tomosynthesis as a stand-alone breast cancer screening modality: results from the Malmö Breast Tomosynthesis Screening Trial, a population-based study All-cause mortality among breast cancer patients in a screening trial: support for breast cancer mortality as an end point Canadian National Breast Screening Study: 1. Breast cancer detection and death rates among women aged 40 to 49 years. False positives in breast cancer screening with one-view breast tomosynthesis: An analysis of findings leading to recall, work-up and biopsy rates in the Malmö Breast Tomosynthesis Screening Trial Breast cancer detection using automated whole breast ultrasound and mammography in radiographically dense breasts Primary and adjuvant therapy, prognostic factors and survival in 1053 breast cancers diagnosed in a trial of mammography screening. Effect of mammographic screening from age 40 years on breast cancer mortality in the UK Age trial at 17 years' follow-up: a randomised controlled trial. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial Comparison of digital mammography alone and digital mammography plus tomosynthesis in a population-based screening program. Screening outcomes in older US women undergoing multiple mammograms in community practice: does interval, age, or comorbidity score affect tumor characteristics or false positive rates? The Canadian National Breast Screening Study-1: Breast Cancer Mortality after 11 to 16 Years of Follow-up: A Randomized Screening Trial of Mammography in Women Age 40 to 49 Years Two-view digital breast tomosynthesis screening with synthetically reconstructed projection images: comparison with digital breast tomosynthesis with full-field digital mammographic images. Outcome analysis for women undergoing annual versus biennial screening mammography: a review of 24,211 examinations. The Gothenburg Breast Screening Trial Accuracy of GE digital breast tomosynthesis vs supplementary mammographic views for diagnosis of screen-detected soft-tissue breast lesions. Breast Tumor Prognostic Characteristics and Biennial vs Annual Mammography, Age, and Menopausal Status. Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection-a novel approach to breast cancer screening with MRI. Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study. Analysis of breast cancer mortality and stage distribution by age for the Health Insurance Plan clinical trial. Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk. Supplemental Breast MR Imaging Screening of Women with Average Risk of Breast Cancer. Canadian National Breast Screening Study: 2. Breast cancer detection and death rates among women aged 50 to 59 years. Efficacy of breast cancer screening by age. New results swedish two‐county trial Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan. Age-specific reduction in breast cancer mortality by screening: an analysis of the results of the Health Insurance Plan of Greater New York study. Use of single-view digital breast tomosynthesis (DBT) and ultrasound vs. additional views and ultrasound for the assessment of screen-detected abnormalities: German multi-reader study Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial). Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. Sensitivity and specificity of mammography and adjunctive ultrasonography to screen for breast cancer in the Japan Strategic Anti-cancer Randomized Trial (J-START): a randomised controlled trial Digital Mammography versus Digital Mammography Plus Tomosynthesis for Breast Cancer Screening: The Reggio Emilia Tomosynthesis Randomized Trial. One-view breast tomosynthesis versus two-view mammography in the Malmö Breast Tomosynthesis Screening Trial (MBTST): a prospective, population-based, diagnostic accuracy study. Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians Methods for Development of the European Commission Initiative on Breast Cancer Guidelines Outcomes of screening mammography by frequency, breast density, and postmenopausal hormone therapy. Benefits, Harms, and Cost-Effectiveness of Supplemental Ultrasonography Screening for Women With Dense Breasts
abstract: Abstract Objectives To compare double readings when interpreting full field digital mammography ( 2D ) and tomo synthesis ( 3D )  during mammographic screening . Methods A prospect i ve , Ethical Committee approved screening study is underway . During the first year 12,621 consenting women underwent both 2D and 3D imaging .  Each examination was independently interpreted by four radiologists under four reading modes : Arm A—2D ; Arm B—2D + CAD ; Arm C—2D + 3D ; Arm D— synthesis ed 2D + 3D . Examinations with a positive score by at least one reader were discussed at an arbitration meeting before a final management decision . Paired double reading of 2D ( Arm A + B ) and 2D + 3D ( Arm C + D ) were analysed . Performance measures were compared using generalised linear mixed models , accounting for inter-reader performance heterogeneity ( P < 0.05 ) . Results Pre-arbitration false-positive scores were 10.3 % ( 1,286/12,501 ) and 8.5 % ( 1,057/12,501 ) for 2D and 2D + 3D , respectively ( P < 0.001 ) . Recall rates were 2.9 % ( 365/12,621 ) and 3.7 % ( 463/12,621 ) , respectively ( P = 0.005 ) . Cancer detection was 7.1 ( 90/12,621 ) and 9.4 ( 119/12,621 ) per 1,000 examinations , respectively ( 30 % increase , P < 0.001 ) ; positive predictive values ( detected cancer patients per 100 recalls ) were 24.7 % and 25.5 % , respectively ( P = 0.97 ) . Using 2D + 3D , double-reading radiologists detected 27 additional invasive cancers ( P < 0.001 ) . Conclusion Double reading of 2D + 3D significantly improves the cancer detection rate in mammography screening . Key Points• Tomo synthesis -based screening was successfully implemented in a large prospect i ve screening trial . • Double reading of tomo synthesis -based examinations significantly reduced false-positive interpretations . • Double reading of tomo synthesis significantly increased the detection of invasive cancers 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 Purpose Digital breast tomo synthesis ( DBT ) has the potential to overcome limitations of conventional mammography . This study investigated the effects of addition of DBT on  interval and detected cancers in population -based screening . Methods Oslo Tomo synthesis Screening Trial ( OTST ) was a prospect i ve , independent double-reading trial inviting women 50–69 years biennially , comparing full-field digital mammography ( FFDM ) plus DBT with FFDM alone .  Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds . Results 24,301 consenting women underwent FFDM + DBT screening over a 2-year period . Results were compared with 59,877 FFDM examinations during prior rounds . Addition of DBT result ed in a non-significant increase in sensitivity ( 76.2 % , 378/496 , vs. 80.8 % , 227/281 , p = 0.151 ) and a significant increase in specificity ( 96.4 % , 57229/59381 vs. 97.5 % , 23427/24020 , p < .001 ) . Number of recalls per screen-detected cancer decreased from 6.7 ( 2530/378 ) to 3.6 ( 820/227 ) with DBT ( p < .001 ) . Cancer detection per 1000 women screened increased ( 6.3 , 378/59877 , vs. 9.3 , 227/24301 , p < .001 ) . Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds ( 2.1 , 51/24301 vs. 2.0 , 118/59877 , p = 0.734 ) . Interval cancers post-DBT were comparable to prior rounds but significantly different in size , grade , and node status from cancers detected only using DBT . 39.6 % ( 19/48 ) of interval cancers had positive nodes compared with only 3.9 % ( 2/51 ) of additional DBT-only-detected cancers . Conclusions DBT-supplemented screening result ed in significant increases in screen-detected cancers and specificity . However , no significant change was observed in the rate , size , node status , or grade of interval cancers . Clinical Trials.gov : NCT01248546 Purpose To compare the performance of digital breast tomo synthesis ( DBT ) and two-dimensional synthetic mammography ( SM ) with that of digital mammography ( DM ) in a population -based mammographic screening program . Material s and Methods In this prospect i ve cohort study , data from 37 185 women screened with DBT and SM and from 61 742 women screened with DM as part of a population -based screening program in 2014 and 2015 were included . Early performance measures , including recall rate due to abnormal mammographic findings , rate of screen-detected breast cancer , positive predictive value of recall , positive predictive value of needle biopsy , histopathologic type , tumor size , tumor grade , lymph node involvement , hormonal status , Ki-67 level , and human epidermal growth factor receptor 2 status were compared in women who underwent DBT and SM screening  and in those who underwent DM screening  by using χ2 tests , two- sample unpaired t tests , and tests of proportions . Results Recall rates were 3.4 % for DBT and SM screening and 3.3 % for DM screening ( P = .563 ) . DBT and SM screening showed a significantly higher rate of screen-detected cancer compared with DM screening ( 9.4 vs 6.1 cancers per 1000 patients screened , respectively ; P < .001 ) . The rate of detection of tumors 10 mm or smaller was 3.2 per 1000 patients screened with DBT and SM and 1.8 per 1000 patients screened with DM ( P < .001 ) , and the rate of grade 1 tumors was 3.3 per 1000 patients screened with DBT and SM versus 1.4 per 1000 patients screened with DM ( P < .001 ) . On the basis of immunohistochemical analyses , rates of lymph node involvement and tumor subtypes did not differ between women who underwent DBT and SM screening and those who underwent DM screening . Conclusion DBT and SM screening increased the detection rate of histologically favorable tumors compared with that attained with DM screening . © RSNA , 2018 Online supplemental material is available for this article BACKGROUND Breast tomo synthesis ( pseudo-3D mammography ) improves breast cancer detection when added to 2D mammography . In this study , we examined whether integrating 3D mammography with either st and ard 2D mammography acquisitions or with synthetic 2D images ( reconstructed from 3D mammography ) would detect more cases of breast cancer than 2D mammography alone , to potentially reduce the radiation burden from the combination of 2D plus 3D acquisitions . METHODS The Screening with Tomo synthesis Or st and ard Mammography-2 ( STORM-2 ) study was a prospect i ve population -based screening study comparing integrated 3D mammography ( dual-acquisition 2D-3D mammography or 2D synthetic-3D mammography ) with 2D mammography alone . Asymptomatic women aged 49 years or older who attended population -based screening in Trento , Italy were recruited for the study . All participants underwent digital mammography with 2D and 3D mammography acquisitions , with the use of software that allowed synthetic 2D mammographic images to be reconstructed from 3D acquisitions . Mammography screen-reading was done in two parallel double-readings conducted sequentially for 2D acquisitions followed by integrated acquisitions . Recall based on a positive mammography result was defined as recall at any screen read . Primary outcome measures were a comparison between integrated ( 2D-3D or 2D synthetic-3D ) mammography and 2D mammography alone of the number of cases of screen-detected breast cancer , the cancer detection rate per 1000 screens , the incremental cancer detection rate , and the number and percentage of false-positive recalls . FINDINGS Between May 31 , 2013 , and May 29 , 2015 , 10 255 women were invited to participate , of whom 9672 agreed to participate and were screened . In these 9672 participants ( median age 58 years [ IQR 53 - 63 ] ) , screening detected 90 cases of breast cancer , including 74 invasive breast cancers , in 85 women ( five women had bilateral breast cancer ) . To account for these bilateral cancers in cancer detection rate estimates , the number of screens used for analysis was 9677 . Both 2D-3D mammography ( cancer detection rate 8·5 per 1000 screens [ 82 cancers detected in 9677 screens ] ; 95 % CI 6·7 - 10·5 ) and 2D synthetic-3D mammography ( 8·8 per 1000 [ 85 in 9677 ] ; 7·0 - 10·8 ) had significantly higher rates of breast cancer detection  than 2D mammography alone ( 6·3 per 1000 [ 61 in 9677 ] , 4·8 - 8·1 ; p<0·0001 for both comparisons ) . The cancer detection rate did not differ significantly between 2D-3D mammography and 2D synthetic-3D mammography ( p=0·58 ) . Compared with 2D mammography alone , the incremental cancer detection rate from 2D-3D mammography was 2·2 per 1000 screens ( 95 % CI 1·2 - 3·3 ) and that from 2D synthetic-3D mammography was 2·5 per 1000 ( 1·4 - 3·8 ) . Compared with the proportion of false-positive recalls from 2D mammography alone ( 328 of 9587 participants not found to have cancer at assessment ) [ 3·42 % ; 95 % CI 3·07 - 3·80 ] ) , false-positive recall was significantly higher for 2D-3D mammography ( 381 of 9587 [ 3·97 % ; 3·59 - 4·38 ] , p=0·00063 ) and for 2D synthetic-3D mammography ( 427 of 9587 [ 4·45 % ; 4·05 - 4·89 ] , p<0·0001 ) . INTERPRETATION Integration of 3D mammography ( 2D-3D or 2D synthetic-3D ) detected more cases of breast cancer  than 2D mammography alone , but increased the percentage of false-positive recalls in sequential screen-reading . These results should be considered in the context of the trade-off between benefits and harms inherent in population breast cancer screening , including that significantly increased breast cancer detection from integrating 3D mammography into screening has the potential to augment screening benefit and also possibly contribute to overdiagnosis . FUNDING None BACKGROUND & METHODS The prospect i ve ' screening with tomo synthesis or st and ard mammography ' ( STORM ) trial recruited women participating in biennial breast screening in Italy ( 2011 - 2012 ) , and compared sequential screen-readings based on 2D-mammography alone or based on tomo synthesis ( integrated 2D/3D-mammography ) . The STORM trial showed that tomo synthesis screen-reading significantly increased breast cancer detection compared to 2D-mammography alone . The present study completes reporting of the trial by examining interval breast cancers ascertained at two year follow-up . RESULTS 9 interval breast cancers were identified ; the estimated interval cancer rate was 1.23/1000 screens [ 9/7292 ] ( 95%CI 0.56 to 2.34 ) or 1.24/1000 negative screens [ 9/7235 ] ( 95%CI 0.57 to 2.36 ) . In concurrently screened women who attended the same screening services and received 2D-mammography , interval cancer rate was 1.60/1000 screens [ 40/25,058 ] ( 95 % CI 1.14 to 2.17 ) or 1.61/1000 negative screens [ 40/24,922 ] ( 95 % CI 1.15 to 2.18 ) . Estimated screening sensitivity for the STORM trial was 85.5 % [ 59/69 ] ( 95%CI 75.0%-92.8 % ) , and that for 2D-mammography screening was 77.3 % [ 136/176 ] ( 95%CI 70.4%-83.2 % ) . CONCLUSION Interval breast cancer rate amongst screening participants in the STORM trial was marginally lower ( and screening sensitivity higher ) than estimates amongst 2D-screened women ; these findings should be interpreted with caution given the small number of interval cases and the sample size of the trial . Much larger screening studies , or pooled analyses , are required to examine interval cancer rates arising after breast tomo synthesis screening versus digital mammography screening OBJECTIVE The aim of this study was to supplement the paucity of information available on logistical aspects of the application of three-dimensional ( 3D ) mammography in breast screening . METHODS We prospect ively examined the effect on radiographers ' and radiologists ' workload of implementing 3D mammography in screening by comparing image acquisition time and screen-reading time for two-dimensional ( 2D ) mammography with that of combined 2D+3D mammography .  Radiologists ' accuracy was also calculated . RESULTS Average acquisition time ( measured from start of first-view breast positioning to compression release at completion of last view ) for seven radiographers , based on 20 screening examinations , was longer for 2D+3D ( 4 min 3 s ; range 3 min 53 s-4 min 18 s ) than 2D mammography ( 3 min 13 s ; range 3 min 0 s-3 min 26 s ; p<0.01 ) . Average radiologists ' reading time per screening examination ( three radiologists reading case-mix of 100 screens : 10 cancers , 90 controls ) was longer for 2D+3D ( 77 s ; range 60 - 90 s ) than for 2D mammography ( 33 s ; range 25 - 46 s ; p<0.01 ) . 2D+3D  screen-reading was associated with detection of more cancers and with substantially fewer recalls than 2D mammography alone . CONCLUSION Relative to st and ard 2D mammography , combined 2D+3D mammography prolongs image acquisition time and screen-reading time ( at initial implementation ) , and appears to be associated with improved screening accuracy . ADVANCES IN KNOWLEDGE These findings provide relevant information to guide larger trials of integrated 3D mammography ( 2D+3D ) and its potential implementation into screening practice PURPOSE We compared detection measures for breast screening strategies comprising single-reading or double-reading using st and ard 2D-mammography or 2D/3D-mammography , based on the ' screening with tomo synthesis or st and ard mammography ' ( STORM ) trial . METHODS STORM prospect ively examined screen-reading in two sequential phases , 2D-mammography alone and integrated 2D/3D-mammography , in asymptomatic women participating in Trento and Verona ( Northern Italy ) population -based screening services . Outcomes were ascertained from assessment and /or excision histology or follow-up . For each screen-reading strategy we calculated the number of detected and non-detected ( including interval ) cancers , cancer detection rates ( CDRs ) , false positive recall ( FPR ) measures and incremental CDR relative to a comparator strategy . We estimated the false : true positive ( FP : TP ) ratio and sensitivity of each mammography screening strategy . Paired binary data were compared using McNemar 's test . RESULTS Amongst 7292 screening participants , there were 65 ( including six interval ) breast cancers ; estimated first-year interval cancer rate was 0.82/1000 screens ( 95 % confidence interval ( CI ) : 0.30 - 1.79/1000 ) . For single-reading , 35 cancers were detected at both 2D and 2D/3D-mammography , 20 cancers were detected only with 2D/3D-mammography compared with none at 2D-mammography alone ( p<0.001 ) and 10 cancers were not detected . For double-reading , 39 cancers were detected at 2D-mammography and 2D/3D-mammography , 20 were detected only with 2D/3D-mammography compared with none detected at 2D-mammography alone ( p<0.001 ) and six cancers were not detected . The incremental CDR attributable to 2D/3D-mammography ( versus 2D-mammography ) of 2.7/1000 screens ( 95 % CI : 1.6 - 4.2 ) was evident for single and for double-reading . Incremental CDR attributable to double-reading ( versus single-reading ) of 0.55/1000 screens ( 95 % CI : -0.02 - 1.4 ) was evident for 2D-mammography and for 2D/3D-mammography .  Estimated FP : TP ratios showed that 2D/3D-mammography screening strategies had more favourable FP to TP trade-off and higher sensitivity , applying single-reading or double-reading , relative to 2D-mammography screening . CONCLUSION The evidence we report warrants rethinking of breast screening strategies and should be used to inform future evaluations of 2D/3D-mammography that assess whether or not the estimated incremental detection translates into improved screening outcomes such as a reduction in interval cancer rates Abstract Objective To assess the performance of one-view digital breast tomo synthesis ( DBT ) in breast cancer screening . Methods The Malmö Breast Tomo synthesis Screening Trial is a prospect i ve population -based one-arm study with a planned inclusion of 15000 participants ; a r and om sample of women aged 40–74 years eligible for the screening programme . This is an explorative analysis of the first half of the study population ( n = 7500 ) . Participants underwent one-view DBT and two-view digital mammography ( DM ) , with independent double reading and scoring . Primary outcome measures were detection rate , recall rate and positive predictive value ( PPV ) . McNemar 's test with 95 % confidence intervals was used . Results Breast cancer was found in sixty-eight women . Of these , 46 cases were detected by both modalities , 21 by DBT alone and one by DM alone . The detection rate for one-view DBT was 8.9/1000 screens ( 95 % CI 6.9 to 11.3 ) and 6.3/1000 screens ( 4.6 to 8.3 ) for two-view DM ( p < 0.0001 ) . The recall rate after arbitration was 3.8 % ( 3.3 to 4.2 ) for DBT and 2.6 % ( 2.3 to 3.0 ) for DM ( p < 0.0001 ) . The PPV was 24 % for both DBT and DM . Conclusion Our results suggest that one-view DBT might be feasible as a st and -alone screening modality . Key Points• One-view DBT as a st and -alone breast cancer screening modality has not been investigated . • One-view DBT increased the cancer detection rate significantly . • The recall rate increased significantly but was still low . • Breast cancer screening with one-view DBT as a st and -alone modality seems feasible BACKGROUND : It has recently been suggested that all-cause mortality is a more appropriate end point than disease specific mortality in cancer screening trials , and that disease specific mortality is biased in favour of screening . This suggestion is based partly on supposed inconsistencies between all-cause mortality results and disease specific results in cancer screening trials , and alleged increases in deaths from causes other than breast cancer among breast cancer cases diagnosed among women invited to screening . METHODS : We used data from the Swedish Two-County Trial of mammographic screening for breast cancer , in which 77 080 women were r and omised to an invitation to screening and 55 985 to no invitation .  We estimated relative risks ( RRs ) ( invited v control ) of death from breast cancer , death from other causes within the breast cancer cases , and death from all causes within the breast cancer cases . RRs were adjusted for age and took account of the longer follow up of breast cancer cases in the invited group due to lead time . RESULTS : There was a significant 31 % reduction in breast cancer mortality in the invited group ( RR 0.69 , 95 % confidence interval ( CI ) 0.58–0.80 ; p<0.001 ) . There was no significant increase in deaths from other causes among breast cancer cases in the invited group ( RR 1.12 , 95 % CI 0.96–1.31 ; p=0.14 ) . A significant 19 % reduction in deaths from all causes was observed among breast cancer cases in the group invited to screening ( RR 0.81 , 95 % CI 0.72–0.90 ; p<0.001 ) . A more conservative estimation gave a significant 13 % reduction ( RR 0.87 , 95 % CI 0.78–0.97 ; p=0.01 ) . These findings are consistent with the magnitude of the reduction in breast cancer mortality . CONCLUSIONS : Invitation to screening was associated with a reduction in deaths from all causes among breast cancer cases , consistent with high participation rates in screening . There is no significant evidence of bias in cause of death classification in the Two-County Trial , and as breast cancer mortality is the targeted clinical outcome in breast cancer screening , it is the appropriate end point in a breast cancer screening trial . All-cause mortality is a poor and inefficient surrogate for breast cancer mortality 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 Abstract Objectives To analyse false positives ( FPs ) in breast cancer screening with tomo synthesis ( BT ) vs. mammography ( DM ) . Methods The Malmö Breast Tomo synthesis Screening Trial ( MBTST ) is a prospect i ve population -based study comparing one-view BT to DM in screening . This study is based on the first half of the MBTST population ( n = 7,500 ) .  Differences in FP recall rate , findings leading to recall , work-up and biopsy rate between cases recalled on BT alone , DM alone and BT+DM were analysed . Results The FP recall rate  was 1.7 % for  BT alone  ( n = 131 ) , 0.9 % for DM alone ( n = 69 ) and 1.1 % for BT + DM ( n = 81 ) . The FP recall rate for BT alone was halved after the initial phase of the trial , stabilising at 1.5 % . BT doubled the recall of stellate distortions compared to DM ( n = 64 vs. n = 33 ) . There were fewer fibroadenomas and cysts , and the biopsy rate was slightly lower for FP recalled on BT alone compared to DM alone ( 15.3 % vs. 27.6 % : p = 0.037 and 33.8 % vs. 36.2 % ; p = 0.641 , respectively ) . Conclusions FPs increased with BT screening mainly due to the recall of stellate distortions . The FP recall rate was still well within the European guidelines and showed evidence of a learning curve . Characterisation of rounded lesions was improved with BT.Key Points• Tomo synthesis screening gave a higher false-positive recall rate than mammography • There was a decline in the false-positive recall rate for tomo synthesis • The recall due to stellate distortions simulating malignancy was doubled with tomo synthesis • Tomo synthesis found more radial and postoperative scar tissue than mammography • Tomo synthesis is better at characterising rounded Purpose Mammography , the st and ard method of breast cancer screening , misses many cancers , especially in dense-breasted women . We compared the performance and diagnostic yield of mammography alone versus an automated whole breast ultrasound ( AWBU ) plus mammography in women with dense breasts and /or at elevated risk of breast cancer . Methods AWBU screening was tested in 4,419 women having routine mammography ( Trial Registration : Clinical Trials.gov Identifier : NCT00649337 ) . Cancers occurring during the study and subsequent 1-year follow-up were evaluated . Sensitivity , specificity and positive predictive value ( PPV ) of biopsy recommendation for mammography alone , AWBU and mammography with AWBU were calculated . Results Breast cancer detection doubled from 23 to 46 in 6,425 studies using AWBU with mammography , result ing in an increase in diagnostic yield from 3.6 per 1,000 with mammography alone to 7.2 per 1,000 by adding AWBU . PPV for biopsy based on mammography findings was 39.0 % and for AWBU 38.4 % . The number of detected invasive cancers 10 mm or less in size tripled from 7 to 21 when AWBU findings were added to mammography . Conclusion AWBU result ed in significant cancer detection improvement compared with mammography alone . Additional detection and the smaller size of invasive cancers may justify this technology ’s expense for women with dense breasts and /or at high risk for breast cancer BACKGROUND As mammographic screening becomes more widespread , larger numbers of tumours are diagnosed while small and node negative . METHODS We examined detection mode , tumour size , node status , histological type , therapy and outcome in 1053 breast cancers diagnosed in one county of the Swedish Two-County Trial of mammographic screening for breast cancer . RESULTS Of patients undergoing total mastectomy with axillary dissection  , 65 % were found to be node negative . For tumours of size 1 - 9 mm , 95 % were node negative . The major effects on survival were tumour size , node status and histological type .  Primary adjuvant therapy had no significant association with survival . CONCLUSIONS The advent of mammography has substantially enhanced the possibilities for less radical treatment . There is an urgent need for therapeutic trials utilizing mammographic-pathological correlations to ascertain in advance which tumours can and which can not benefit from more radical therapy 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 breast cancers were over-diagnosed , representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial PURPOSE To assess cancer detection rates , false-positive rates before arbitration , positive predictive values for women recalled after arbitration , and the type of cancers detected with use of digital mammography alone and combined with tomo synthesis in a large prospect i ve screening trial . MATERIAL S AND METHODS A prospect i ve , reader- and modality-balanced screening study of participants undergoing combined mammography plus tomo synthesis , the results of which were read independently by four different radiologists , is under way . The study was approved by a regional ethics committee , and all participants provided written informed consent . The authors performed a preplanned interim analysis of results from 12,631 examinations interpreted by using mammography alone and mammography plus tomo synthesis from November 22 , 2010 , to December 31 , 2011 . Analyses were based on marginal log-linear models for binary data , accounting for correlated interpretations and adjusting for reader-specific performance levels by using a two-sided significance level of .0294 . RESULTS Detection rates , including those for invasive and in situ cancers , were 6.1 per 1000 examinations for mammography alone and 8.0 per 1000 examinations for mammography plus tomo synthesis ( 27 % increase , adjusted for reader ; P = .001 ) . False-positive rates before arbitration were 61.1 per 1000 examinations with mammography alone and 53.1 per 1000 examinations with mammography plus tomo synthesis ( 15 % decrease , adjusted for reader ; P < .001 ) . After arbitration , positive predictive values for recalled patients with cancers verified later were comparable ( 29.1 % and 28.5 % , respectively , with mammography alone and mammography plus tomo synthesis ; P = .72 ) . Twenty-five additional invasive cancers were detected with mammography plus tomo synthesis ( 40 % increase , adjusted for reader ; P < .001 ) . The mean interpretation time was 45 seconds for mammography alone and 91 seconds for mammography plus tomo synthesis ( P < .001 ) . CONCLUSION The use of mammography plus tomo synthesis in a screening environment result ed in a significantly higher cancer detection rate and enabled the detection of more invasive cancers . Clinical trial registration no. NCT01248546 Background Uncertainty exists about the appropriate use of screening mammography among older women because comorbid illnesses may diminish the benefit of screening . We examined the risk of adverse tumor characteristics and false positive rates according to screening interval , age , and comorbidity . Methods From January 1999 to December 2006 , data were collected prospect ively on 2993 older women with breast cancer and 137 949 older women without breast cancer who underwent mammography at facilities that participated in a data linkage between the Breast Cancer Surveillance Consortium and Medicare cl aims . Women were aged 66 to 89 years at study entry to allow for measurement of 1 year of preexisting illnesses . We used logistic regression analyses to calculate the odds of advanced ( IIb , III , IV ) stage , large ( > 20 millimeters ) tumors , and 10-year cumulative probability of false-positive mammography by screening frequency ( 1 vs 2 years ) , age , and comorbidity score . The comorbidity score was derived using the Klabunde approximation of the Charlson score . All statistical tests were two-sided . Results Adverse tumor characteristics did not differ statistically significantly by comorbidity , age , or interval . Cumulative probability of a false-positive mammography result was higher among annual screeners than biennial screeners irrespective of comorbidity : 48.0 % ( 95 % confidence interval [ CI ] = 46.1 % to 49.9 % ) of annual screeners aged 66 to 74 years had a false-positive result compared with 29.0 % ( 95 % CI = 28.1 % to 29.9 % ) of biennial screeners . Conclusion Women aged 66 to 89 years who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of a false-positive recommendation than annual screeners , regardless of comorbidity Context Seven- and 10-year results of the Canadian National Breast Screening Study ( CNBSS ) showed no reduction in breast cancer mortality from five annual mammographies and breast examinations for 40- to 49-year-old women . Some authors have argued that longer follow-up would reveal important benefits . Contribution After 11 to 16 years , the cumulative rate ratios for mammography versus usual care were 0.97 ( 95 % CI , 0.74 to 1.27 ) for breast cancer mortality without adjustment for non study mammography and 1.06 ( CI , 0.80 to 1.40 ) with adjustment . Clinical Implication s The CNBSS suggests that screening 40- to 49-year-old women is unlikely to reduce breast cancer by 20 % or more . Controversy will persist because other studies suggest that screening causes small reductions in breast cancer mortality . The Editors The Canadian National Breast Screening Study -1 ( CNBSS-1 ) , an individually r and omized trial in women 40 to 49 years of age at study entry , evaluated the efficacy of annual mammography , breast physical examination , and instruction on breast self-examination in reducing breast cancer mortality  ( 1 ) . The 7-year ( 2 ) and preliminary 10-year ( 3 ) mortality results were previously reported . At 7 years , 38 women in the mammography group and 28 women in the usual care group had died of breast cancer , for a rate ratio of 1.36 ( 95 % CI , 0.84 to 2.21 ) ( 2 ) . At 10 years , there were 82 breast cancer deaths in the mammography group and 72 in the usual care group ( rate ratio , 1.14 [ CI , 0.83 to 1.56 ] ) ( 3 ) . This article reports CNBSS-1 results after an average 13-year follow-up from study entry . Methods Patient Selection and Recruitment Participants were recruited through media publicity , personal invitation letters using population lists ( municipal registers and provincial health insurance registers ) , group mailings , and physicians ( 4 ) . Eligibility criteria were age 40 to 49 years , no previous diagnosis of breast cancer , not being pregnant , no mammography in the previous 12 months , and signed informed consent . The Human Experimentation Committee of the University of Toronto ( Toronto , Ontario , Canada ) and Human Experimentation Committees at 15 CNBSS collaborating centers approved the study . A total of 50 430 women age 40 to 49 years were enrolled from January 1980 through March 1985 . R and omization Before r and omization , all participants received an initial breast physical examination and instruction on breast self-examination . They were then immediately r and omly assigned to receive mammography and , thereafter , either annual screening with mammography and breast physical examination ( 25 214 women in the mammography group were available for analysis ) or usual care in the context of the Canadian health care system ( 25 216 women in the usual care group were available for analysis ) . Center coordinators r and omly assigned participants using prepared allocation lists , independent of breast physical examination findings . This sequence ensured that the conduct and interpretation of the breast physical examination would be unbiased by knowledge of whether mammography would follow . Intervention Screening Schedule In the mammography group , 62 % of women received five annual screenings . The remainder , recruited later , received four . Each screening examination comprised mammography , breast physical examination , and instruction and evaluation on breast self-examination . Women in the mammography group completed question naires at each rescreening visit . Women in the usual care group were not recalled for rescreening but were mailed annual question naires . We expected that these participants would continue their normal pattern of medical care as delivered through Canada 's universal health care coverage , including access to mammography for diagnosis . Study Procedures Two-view mammography was done on dedicated mammography units ( 5 ) , and second readers review ed mammograms deemed abnormal . Systematic audit procedures were used ( 6 ) . Nurses provided breast physical examination in 12 centers and physicians in 3 centers in Qubec ( 7 ) . These providers taught and evaluated breast self-examination while conducting their own examination ( 8) . If findings on breast physical examination or mammography were abnormal , participants were referred to a CNBSS review clinic . The study surgeon discussed mammography findings with the study radiologist , examined the participant , and decided whether further diagnostic procedures should be recommended to the woman 's physician . The woman 's physician determined whether and how to implement the study surgeon 's recommendations . Data Collection Protocol During the screening period , the center coordinators collected surgery and pathology reports for breast-related diagnostic and therapeutic procedures . The CNBSS pathologists review ed all slides . If the community and CNBSS pathologist disagreed , a panel of three to five CNBSS pathologists blindedly and independently review ed the slides . Extensive quality control procedures were used during data collection . After the screening centers closed in 1988 , the central CNBSS central office annually followed all women known to have breast cancer until 30 June 1996 , the cut-off for this analysis . Passive follow-up of all participants through linkage with the National Cancer Registry identified new diagnoses of breast cancer in study participants through 31 December 1993 . The central office collected pathology reports for postscreening cases of breast cancer . The community diagnosis was accepted for study purpose s. Family members responding to the annual mailed question naire identified deaths that occurred before completion of a participant 's screening schedule . Thereafter , women not known to have cancer were followed only through registry linkage ; their mammography experience was not traced . However , for women known to have breast cancer , attending physicians received annual requests for up date d clinical information , including death .  Attending physicians , who received annual requests for information on women with breast cancer , reported deaths until 30 June 1996 . Linkage with the Canadian Mortality Data base at Statistics Canada ( including deaths in Canadians who resided in the United States at the time of death ) identified causes of death in the entire cohort until 31 December 1993 . The procedures used to verify deaths from breast cancer were described previously ( 2 ) . Investigative procedures were initiated for women dying with breast cancer ; those whose death certificates mentioned breast cancer ; and those whose cause of death was described as unknown , unknown primary , lung cancer , colon cancer , or liver cancer . The review ers were blinded to study group allocation . All other causes of death were accepted as certified . For the most recent record linkage , more stringent confidentiality requirements exercised by many hospitals hindered verification . Thus , of the breast cancer deaths reported in this paper , a panel review ed 67 % in the mammography group and 77 % in the usual care group . The remaining deaths are as reported on death certificates . Study Outcomes Death due to or probably due to breast cancer was the major study outcome . A previous report of the CNBBS-1 noted axillary node status , as assessed by community pathologists , through 7 years of follow-up ( 2 ) . Subsequently ( 1993 to 1997 ) , to achieve consistent reporting of tumor size , all available material for screening-detected cancer and cancer detected between screenings was re-collected from originating institutions and review ed by one of the CNBSS pathologists or a colleague . Slides were obtained for review for nearly 80 % of requested cases . For the current analysis , pathologists measured the size of small tumors as observed on the slide or the size of the invasive component for mixed invasive and in situ tumors . Statistical Analysis Sample Size The CNBSS-1 was planned to evaluate whether breast cancer mortality would decrease by 40 % in the  mammography group compared with the usual care group after 5 years of follow-up , with a required sample size of 50 000 women ( = 0.05 ; power , 80 % ) ( 1 ) . At 5 years , however , too few women had died of breast cancer for the study to achieve the planned power . Thus , for the first report on breast cancer mortality , we extended follow-up to 7 years ( 2 ) . CNBSS Data base The data base includes records for 50 430 women , including demographic and risk factor variables and results of screening examinations , diagnostic and therapeutic procedures , pathology results , and causes of death . CNBSS Terminology The terms screen 1 , screen 2 , through screen 5 denote events associated with screening examinations in the mammography group . The initial breast physical examination received by the usual care group is called screen 1 . Screening-detected cancers are those diagnosed after a recommendation made by the study surgeon at the CNBSS review clinic . Interval cancers are cases of cancer that occurred less than 12 months after a screening examination at which no recommendation for diagnostic procedures was made . Incident cancers are cases of cancer that occurred more than 12 months after the previous CNBSS screening examination . Statistical Tests The statistical significance of differences in proportions was determined by using the chi-square test ( two-sided = 0.05 ) . For all observed-to-expected ratios , 95 % CIs were computed . Death rates were computed by using person-years based on stratification by quinquennium of age ; we assumed that all women not known to be dead are alive . Age was defined as age at entry . Because all eligible participants were included in the analysis and follow-up , this is an intention-to-treat analysis . Cox proportional-hazards regression was done to examine variables with the most significant independent influence on survival ( 9 ) , using the PHREG program in SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Because the variable allocation to screening was our primary interest , it was PURPOSE To compare the performance of two versions of reconstructed two-dimensional ( 2D ) images in combination with digital breast tomo synthesis ( DBT ) versus the performance of st and ard full-field digital mammography ( FFDM ) plus DBT . MATERIAL S AND METHODS This trial had ethical committee approval , and all participants gave written informed consent . Examinations ( n = 24 901 ) in women between the ages of 50 and 69 years ( mean age , 59.2 years ) were interpreted prospect ively as part of a screening trial that included independent interpretations of FFDM plus DBT and reconstructed 2D images plus DBT . Reconstructed 2D images do not require radiation exposure . Using analyses for binary data that accounted for correlated interpretations and were adjusted for reader-specific volume , two versions ( initial and current ) of reconstructed 2D images used during trial periods 1 ( from November 22 , 2010 , to December 21 , 2011 ; 12 631 women ) and 2 ( from January 20 , 2012 , to December 19 , 2012 ; 12 270 women ) were compared in terms of cancer detection and false-positive rates with the corresponding FFDM plus DBT interpretations . RESULTS Cancer detection rates were 8.0 , 7.4 , 7.8 , and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1 , initial reconstructed 2D images plus DBT in period 1 , FFDM plus DBT in period 2 , and current reconstructed 2D images plus DBT in period 2 , respectively . False-positive scores were 5.3 % , 4.6 % , 4.6 % , and 4.5 % , respectively . Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 ( P = .012 ) but not for period 2 ( ratio = 0.99 ; 95 % confidence interval : 0.88 , 1.11 ; P = .85 ) . CONCLUSION The combination of current reconstructed 2D images and DBT performed comparably to FFDM plus DBT and is adequate for routine clinical use when interpreting screening mammograms OBJECTIVE Our goal was to determine differences in outcome measures between women undergoing annual versus biennial screening mammography .  MATERIAL S AND METHODS A retrospective review of prospect ively collected data on 24,211 consecutive screening mammography examinations was performed in women aged 40 - 79 years , all of whom had undergone previous normal screening mammography . Annual screening and biennial screening were defined as examinations performed 10 - 14 months and 22 - 26 months , respectively , after previous normal screening mammography . The rates of recall , biopsy , cancer detection , and interval cancer for annual and biennial screening cohorts were calculated , as were tumor size , lymph node status , and stage of invasive cancer . Interval cancer cases were identified by linkage with a regional tumor registry . RESULTS Of the 4306 biennially screened women , 160 were recalled ( 3.7 % ) , 45 were biopsied ( 1.0 % ) , and cancer was detected in 19 ( 0.44 % ) . Of the 19,905 annually screened women , 518 were recalled ( 2.6 % ) , 150 were biopsied ( 0.75 % ) , and cancer was detected in 71 ( 0.36 % ) . Of the 3278 registry-linked biennially screened women , five had interval cancer ( 0.15 % ) ; of the 15,031 registry-linked annually screened women , 10 had interval cancer ( 0.07 % ) . For biennial screening-detected cancer and interval invasive cancer combined , the median tumor size was 15 mm , 24 % had lymph node metastasis , and 29 % were stage 2 or higher . For annual screening-detected cancer , these measures were 11 mm , 14 % positive nodes , and 17 % stage 2 + cancer , respectively . CONCLUSION Annual screening mammography results in lower recall rates than does biennial screening ( p < .0001 ) . Moreover , annual screening results in the detection of smaller tumors that have a more favorable prognosis ( p = .04 ) Although there is evidence for a reduction in breast carcinoma mortality with mammographic screening , some doubts have been expressed , and there is still uncertainty regarding the age specific effects OBJECTIVE To compare the accuracy of st and ard supplementary views and GE digital breast tomo synthesis ( DBT ) for assessment of soft-tissue mammographic abnormalities . METHODS Women recalled for further assessment of soft-tissue abnormalities were recruited and received st and ard supplementary views ( typically spot compression views ) and two-view GE DBT . The added value of DBT in the assessment process was determined by analysing data collected prospect ively by radiologists working up the cases . Following anonymization of cases , there was also a retrospective multireader review . The readers first read bilateral st and ard two-view digital mammography ( DM ) together with the supplementary mammographic views and gave a combined score for suspicion of malignancy on a five-point scale . The same readers then read bilateral st and ard two-view DM together with two-view DBT . Pathology data were obtained . Differences were assessed using receiver operating characteristic analysis . RESULTS The study population was 342 lesions in 322 patients . The final diagnosis was malignant in 113 cases ( 33 % ) and benign/normal in 229 cases ( 67 % ) . In the prospect i ve analysis , the performance of two-view DM plus DBT was at least equivalent to the performance of two-view DM and st and ard mammographic supplementary views-the area under the curve ( AUC ) was 0.946 and 0.922 , respectively , which did not reach statistical significance . Similar results were obtained for the retrospective review -AUC was 0.900 ( DBT ) and 0.873 ( supplementary views ) , which did not reach statistical significance . CONCLUSION The accuracy of GE DBT in the assessment of screen detected soft-tissue abnormalities is equivalent to the use of st and ard supplementary mammographic views . ADVANCES IN KNOWLEDGE The vast majority of evidence relating to the use of DBT has been gathered from research using Hologic equipment . This study provides evidence for the use of the commercially available GE DBT system demonstrating that it is at least equivalent to supplementary mammographic views in the assessment of soft-tissue screen-detected abnormalities IMPORTANCE Screening mammography intervals remain under debate in the United States . OBJECTIVE To compare the proportion of breast cancers with less vs more favorable prognostic characteristics in women screening annually vs biennially by age , menopausal status , and postmenopausal hormone therapy ( HT ) use . DESIGN , SETTING , AND PARTICIPANTS This was a study of a prospect i ve cohort from 1996 to 2012 at Breast Cancer Surveillance Consortium facilities . A total of 15,440 women ages 40 to 85 years with breast cancer diagnosed within 1 year of an annual or within 2 years of a biennial screening mammogram .  EXPOSURES We up date d previous analyses by using narrower intervals for defining annual ( 11 - 14 months ) and biennial ( 23 - 26 months ) screening . MAIN OUTCOMES AND MEASURES We defined less favorable prognostic characteristics as tumors that were stage IIB or higher , size greater than 15 mm , positive nodes , and any 1 or more of these characteristics . We used log-binomial regression to model the proportion of breast cancers with less favorable characteristics following a biennial vs annual screen by 10-year age groups and by menopausal status and current postmenopausal HT use . RESULTS Among 15,440 women with breast cancer , most were 50 years or older ( 13,182 [ 85.4 % ] ) , white ( 12,063 [ 78.1 % ] ) , and postmenopausal ( 9823 [ 63.6 % ] ) . Among 2027 premenopausal women ( 13.1 % ) , biennial screeners had higher proportions of tumors that were stage IIB or higher ( relative risk [ RR ] , 1.28 [ 95 % CI , 1.01 - 1.63 ] ; P=.04 ) , size greater than 15 mm ( RR , 1.21 [ 95 % CI , 1.07 - 1.37 ] ; P=.002 ) , and with any less favorable prognostic characteristic ( RR , 1.11 [ 95 % CI , 1.00 - 1.22 ] ; P=.047 ) compared with annual screeners . Among women currently taking postmenopausal HT , biennial screeners tended to have tumors with less favorable prognostic characteristics compared with annual screeners ; however , 95 % CIs were wide , and differences were not statistically significant ( for stage 2B+ , RR , 1.14 [ 95 % CI , 0.89 - 1.47 ] , P=.29 ; size>15 mm , RR , 1.13 [ 95 % CI , 0.98 - 1.31 ] , P=.09 ; node positive , RR , 1.18 [ 95 % CI , 0.98 - 1.42 ] , P=.09 ; any less favorable characteristic , RR , 1.12 [ 95 % CI , 1.00 - 1.25 ] , P=.053 ) . The proportions of tumors with less favorable prognostic characteristics were not significantly larger for biennial vs annual screeners among postmenopausal women not taking HT  ( eg , any characteristic : RR , 1.03 [ 95 % CI , 0.95 - 1.12 ] ; P=.45 ) , postmenopausal HT users after subdividing by type of hormone use ( eg , any characteristic : estrogen+progestogen users , RR , 1.16 [ 95 % CI , 0.91 - 1.47 ] ; P=.22 ; estrogen-only users , RR , 1.14 [ 95 % CI , 0.94 - 1.37 ] ; P=.18 ) , or any 10-year age group ( eg , any characteristic : ages 40 - 49 years , RR , .1.04 [ 95 % CI , 0.94 - 1.14 ] ; P=.48 ; ages 50 - 59 years , RR , 1.03 [ 95 % CI , 0.94 - 1.12 ] ; P=.58 ; ages 60 - 69 years , RR , 1.07 [ 95 % CI , 0.97 - 1.19 ] ; P=.18 ; ages 70 - 85 years , RR , 1.05 [ 95 % CI , 0.94 - 1.18 ] ; P=.35 ) . CONCLUSIONS AND RELEVANCE Premenopausal women diagnosed as having breast cancer following biennial vs annual screening mammography are more likely to have tumors with less favorable prognostic characteristics . Postmenopausal women not using HT who are diagnosed as having breast cancer following a biennial or annual screen have similar proportions of tumors with less favorable prognostic characteristics PURPOSE We investigated whether an abbreviated protocol ( AP ) , consisting of only one pre- and one postcontrast acquisition and their derived images ( first postcontrast subtracted [ FAST ] and maximum-intensity projection [ MIP ] images ) , was suitable for breast magnetic resonance imaging ( MRI ) screening . METHODS We conducted a prospect i ve observational reader study in 443 women at mildly to moderately increased risk who underwent 606 screening MRIs . Eligible women had normal or benign digital mammograms and , for those with heterogeneously dense or extremely dense breasts ( n = 427 ) , normal or benign ultrasounds . Expert radiologists review ed the MIP image first to search for significant enhancement and then review ed the complete AP ( consisting of MIP and FAST images and optionally their nonsubtracted source images ) to characterize enhancement and establish a diagnosis . Only thereafter was the regular full diagnostic protocol ( FDP ) analyzed . RESULTS MRI acquisition time for FDP was 17 minutes , versus 3 minutes for the AP . Average time to read the single MIP and complete AP was 2.8 and 28 seconds , respectively . Eleven breast cancers ( four ductal carcinomas in situ and seven invasive cancers ; all T1N0 intermediate or high grade ) were diagnosed , for an additional cancer yield of 18.2 per 1,000 . MIP readings were positive in 10 ( 90.9 % ) of 11 cancers and allowed establishment of the absence of breast cancer , with a negative predictive value ( NPV ) of 99.8 % ( 418 of 419 ) . Interpretation of the complete AP , as with the FDP , allowed diagnosis of all cancers ( 11 [ 100 % ] of 11 ) . Specificity and positive predictive value ( PPV ) of AP versus FDP were equivalent ( 94.3 % v 93.9 % and 24.4 % v 23.4 % , respectively ) . CONCLUSION An MRI acquisition time of 3 minutes and an expert radiologist MIP image reading time of 3 seconds are sufficient to establish the absence of breast cancer , with an NPV of 99.8 % . With a reading time < 30 seconds for the complete AP , diagnostic accuracy was equivalent to that of the FDP and result ed in an additional cancer yield of 18.2 per 1,000 BACKGROUND Digital breast tomo synthesis with 3D images might overcome some of the limitations of conventional 2D mammography for detection of breast cancer . We investigated the effect of integrated 2D and 3D mammography in population breast-cancer screening . METHODS Screening with Tomo synthesis OR st and ard Mammography ( STORM ) was a prospect i ve comparative study . We recruited asymptomatic women aged 48 years or older who attended population -based breast-cancer screening through the Trento and Verona screening services ( Italy ) from August , 2011 , to June , 2012 . We did screen-reading in two sequential phases-2D only and integrated 2D and 3D mammography-yielding paired data for each screen . St and ard double-reading by breast radiologists determined whether to recall the participant based on positive mammography at either screen read . Outcomes were measured from final assessment or excision histology . Primary outcome measures were the number of detected cancers , the number of detected cancers per 1000 screens , the number and proportion of false positive recalls , and incremental cancer detection attributable to integrated 2D and 3D mammography .  We compared paired binary data with McNemar 's test . FINDINGS 7292 women were screened ( median age 58 years [ IQR 54 - 63 ] ) . We detected 59 breast cancers ( including 52 invasive cancers ) in 57 women . Both 2D and integrated 2D and 3D screening detected 39 cancers . We detected 20 cancers with integrated 2D and 3D only versus none with 2D screening only ( p<0.0001 ) . Cancer detection rates were 5.3 cancers per 1000 screens ( 95 % CI 3.8 - 7.3 ) for 2D only , and 8.1 cancers per 1000 screens ( 6.2 - 10.4 ) for integrated 2D and 3D screening . The incremental cancer detection rate attributable to integrated 2D and 3D mammography was 2.7 cancers per 1000 screens ( 1.7 - 4.2 ) . 395 screens ( 5.5 % ; 95 % CI 5.0 - 6.0 ) result ed in false positive recalls : 181 at both screen reads , and 141 with 2D only versus 73 with integrated 2D and 3D screening ( p<0.0001 ) . We estimated that conditional recall ( positive integrated 2D and 3D mammography as a condition to recall ) could have reduced false positive recalls by 17.2 % ( 95 % CI 13.6 - 21.3 ) without missing any of the cancers detected in the study population . INTERPRETATION Integrated 2D and 3D mammography improves breast-cancer detection and has the potential to reduce false positive recalls . R and omised controlled trials are needed to compare integrated 2D and 3D mammography with 2D mammography for breast cancer screening . FUNDING National Breast Cancer Foundation , Australia ; National Health and Medical Research Council , Australia ; Hologic , USA ; Technologic , Italy The Health Insurance Plan ( HIP ) of Greater New York conducted a clinical trial to determine if screening for breast cancer with mammography and clinical examination would decrease breast cancer mortality . The extent of disease at diagnosis among breast cancers detected by screening and the effect of screening on breast cancer mortality have been evaluated in the cohort of all HIP women diagnosed with breast cancer within 6 years of entry into the trial and followed at least 18 years after trial entry . Six years was the earliest time at which the number of cases diagnosed in the control group was equal to the number of cases diagnosed in the study group . In the cohorts of women 40 - 49 and 50 - 64 years of age at entry , shifts were significant to lower stages for screen-detected cases . As a result , the study group women in each age cohort had significantly lower breast cancer mortality than control group women when statistical analyses were restricted to data from cases only . In the 40 - 49 age-at-entry cohort , the reduced breast cancer mortality in the study group appears to result from lower mortality in stage I cases as well as from earlier case detection , and this may explain differences between the two age-at-entry cohorts in the length of follow-up time required to demonstrate a mortality reduction due to screening CONTEXT Annual ultrasound screening may detect small , node-negative breast cancers that are not seen on mammography . Magnetic resonance imaging ( MRI ) may reveal additional breast cancers missed by both mammography and ultrasound screening . OBJECTIVE To determine supplemental cancer detection yield of ultrasound and MRI in women at elevated risk for breast cancer . DESIGN , SETTING , AND PARTICIPANTS From April 2004-February 2006 , 2809 women at 21 sites with elevated cancer risk and dense breasts consented to 3 annual independent screens with mammography and ultrasound in r and omized order . After 3 rounds of both screenings , 612 of 703 women who chose to undergo an MRI  had complete data . The reference st and ard was defined as a combination of pathology ( biopsy results that showed in situ or infiltrating ductal carcinoma or infiltrating lobular carcinoma in the breast or axillary lymph nodes ) and 12-month follow-up . MAIN OUTCOME MEASURES Cancer detection rate ( yield ) , sensitivity , specificity , positive predictive value ( PPV3 ) of biopsies performed and interval cancer rate . RESULTS A total of 2662 women underwent 7473 mammogram and ultrasound screenings  , 110 of whom had 111 breast cancer events : 33 detected by mammography only , 32 by ultrasound only , 26 by both , and 9 by MRI after mammography plus ultrasound ; 11 were not detected by any imaging screen . Among 4814 incidence screens in the second and third years combined , 75 women were diagnosed with cancer . Supplemental incidence-screening ultrasound identified 3.7 cancers per 1000 screens ( 95 % CI , 2.1 - 5.8 ; P < .001 ) . Sensitivity for  mammography plus ultrasound  was 0.76 ( 95 % CI , 0.65 - 0.85 ) ; specificity , 0.84 ( 95 % CI , 0.83 - 0.85 ) ; and PPV3 , 0.16 ( 95 % CI , 0.12 - 0.21 ) . For mammography alone , sensitivity was 0.52 ( 95 % CI , 0.40 - 0.64 ) ; specificity , 0.91 ( 95 % CI , 0.90 - 0.92 ) ; and PPV3 , 0.38 ( 95 % CI , 0.28 - 0.49 ; P < .001 all comparisons ) . Of the MRI participants , 16 women ( 2.6 % ) had breast cancer diagnosed . The supplemental yield of MRI  was 14.7 per 1000 ( 95 % CI , 3.5 - 25.9 ; P = .004 ) . Sensitivity for MRI and mammography plus ultrasound was 1.00 ( 95 % CI , 0.79 - 1.00 ) ; specificity , 0.65 ( 95 % CI , 0.61 - 0.69 ) ; and PPV3 , 0.19 ( 95 % CI , 0.11 - 0.29 ) . For mammography and ultrasound , sensitivity was 0.44 ( 95 % CI , 0.20 - 0.70 , P = .004 ) ; specificity 0.84 ( 95 % CI , 0.81 - 0.87 ; P < .001 ) ; and PPV3 , 0.18 ( 95 % CI , 0.08 to 0.34 ; P = .98 ) . The number of screens needed to detect 1 cancer was 127 ( 95 % CI , 99 - 167 ) for mammography ; 234 ( 95 % CI , 173 - 345 ) for supplemental ultrasound ; and 68 ( 95 % CI , 39 - 286 ) for MRI after negative mammography and ultrasound results . CONCLUSION The addition of screening ultrasound or MRI to mammography in women at increased risk of breast cancer result ed in not only a higher cancer detection yield but also an increase in false-positive findings . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00072501 Purpose To investigate the utility and accuracy of breast magnetic resonance ( MR ) imaging as a supplemental screening tool in women at average risk for breast cancer and to investigate the types of cancer detected with MR imaging screening . Material s and Methods This prospect i ve observational study was conducted at two academic breast centers in women aged 40 - 70 years without breast cancer-associated risk factors ( lifetime risk < 15 % ) . Between January 2005 and December 2013 , women with at least minimal residual breast tissue ( American College of Radiology categories A-D ) and normal conventional imaging findings ( screening mammography with or without screening ultrasonography [ US ] )  were invited to undergo supplemental MR imaging screening . Outcome measures were supplemental cancer detection rates , interval cancer rates , and biologic profiles of MR imaging-detected additional cancers , as well as specificity and positive predictive value ( PPV ) of MR imaging screening . Tissue diagnoses or 2 years of follow-up were used to establish the reference st and ard . Results A total of 2120 women were recruited and underwent 3861 screening MR imaging studies  , covering an observation period of 7007 women-years . Breast MR imaging depicted 60 additional breast cancers ( ductal carcinoma in situ , n = 20 ; invasive carcinoma , n = 40 ) for an overall supplemental cancer detection rate of 15.5 per 1000 cases ( 95 % confidence interval [ CI ] : 11.9 , 20.0 ) . Forty-eight additional cancers were detected with MR imaging at initial screening ( supplemental cancer detection rate , 22.6 per 1000 cases ) . During the 1741 subsequent screening rounds , 12 of 13 incident cancers were found with MR imaging alone ( supplemental cancer detection rate , 6.9 per 1000 cases ) . One cancer was diagnosed with all three methods ( mammography , US , and MR imaging ) , and none were diagnosed with mammography only or US only . Cancers diagnosed with MR imaging were small ( median , 8 mm ) , node negative in 93.4 % of cases , and dedifferentiated ( high- grade cancer ) in 41.7 % of cases at prevalence screening and 46.0 % of cases at incidence screening . No interval cancers were observed . MR imaging screening offered high specificity ( 97.1 % ; 95 % CI : 96.5 , 97.6 ) and high PPV ( 35.7 % ; 95 % CI : 28.9 , 43.1 ) . Conclusion In women at average risk for breast cancer , MR imaging screening improves early diagnosis of prognostically relevant breast cancer . © RSNA , 2017 Online supplemental material is available for this article OBJECTIVE To evaluate the efficacy of annual mammography over and above annual physical examination of the breasts and the teaching of breast self-examination among women aged 50 to 59 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 annual physical examination only ( PO group ) . The 39,405 women enrolled from January 1980 through March 1985 were followed for a mean of 8.3 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 85 % of the women in each group attended the screening sessions after screen 1 . 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 7.20 per 1000 in the MP group and 3.45 per 1000 in the PO group , more node-positive tumours were found in the MP group than in the PO group . At subsequent screens the detection rates were a little less than half the rates at screen 1 . During years 2 through 5 the ratios of observed to expected cases of invasive breast cancer were 1.28 in the MP group and 1.18 in the PO group . Of the women with invasive breast cancer through to 7 years , 217 in the MP group and 184 in the PO group had no node involvement , 66 and 56 had one to three nodes involved , 32 and 34 had four or more nodes involved , and 55 and 46 had an unknown nodal status . There were 38 deaths from breast cancer in the MP group and 39 in the PO group . The ratio of the proportions of death from breast cancer in the MP group compared with those in the UC group was 0.97 ( 95 % confidence interval 0.62 to 1.52 ) . The survival rates were similar in the two groups . Women whose cancer had been detected by mammography alone had the highest survival rate . CONCLUSION The study was internally valid , and there was no evidence of r and omization bias . Screening with yearly mammography in addition to physical examination of the breasts detected considerably more node-negative , small tumours than screening with physical examination alone , but it had no impact on the rate of death from breast cancer up to 7 years ' follow-up from entry Background . Several studies have found a smaller effect of breast cancer screening on breast cancer mortality in women aged younger than 50 years compared with older women . Various possible reasons have been suggested for this , but none firmly is established This paper summarizes the findings of the first breast cancer screening trial , which was initiated in December 1963 to explore the efficacy of screening . Women aged 40 - 64 years were selected from enrollees in the Health Insurance Plan ( HIP ) of Greater New York and were r and omly assigned to study and control groups . Study group women were invited for screening , an initial examination , and three annual reexaminations . Screening consisted of film mammography ( cephalocaudal and lateral views of each breast ) and clinical examination of breasts .  Breast cancer and mortality from breast cancer were examined by treatment group ( study vs. control ) and by entry-age subgroup . By the end of 18 years from entry , the study group had about a 25 % lower breast cancer mortality among women aged 40 - 49 and 50 - 59 at time of entry than did the control group . However , to a large extent the difference among the 40 - 49-year-olds occurred in the subgroup with breast cancer diagnosed after these women had passed their 50th birthday , and utility of screening women in their forties is question able The 14-year follow-up mortality results from the r and omized breast cancer screening trial of the Health Insurance Plan of Greater New York ( HIP ) were analyzed with respect to the problem of age-specific screening effects . Mortality reduction was measured in three different ways and appears to be homogeneous across age groups . This finding challenges the widespread opinion that the results of the HIP study support the conclusion that breast cancer screening is not effective below age 50 Background Data on the value of digital breast tomo synthesis ( DBT ) for further assessment of screen-detected lesions are still limited . Purpose To compare screening mammography , single-view DBT and ultrasound-information ( TS ) vs. screening mammography , additional views and ultrasound-information ( AV ) for assessment of screen-detected abnormalities . Material and Methods The use of wide-angle DBT for screen-detected , soft-tissue abnormalities requiring additional views was investigated : 241 cases ( 206 benign and 35 malignant lesions ) , verified by histology or two-year follow-up , were read by ten readers as TS and as AV sets , yielding 2410 diagnoses for each set . Readings were r and omly sequenced . Results The mean interval between readings was nine weeks ( r and om sequence ) . Evaluation was breast-based . Overall , in terms of area under receiver operating characteristic ( AUC ; varying degree of suspicion cutoff ) , TS and AV readings showed similar performance : for TS , AUC was 0.889 ( 95 % confidence interval [ CI ] = 0.871–0.907 ) and for AV , AUC was 0.903 ( 95 % CI = 0.886–0.921 ) . TS readings had slightly higher sensitivity than AV readings ( 96.9 % vs. 95.4 % ) but lower specificity ( 50 % vs. 58.1 % ) and more variations between reader performance ; absolute false negatives ( FN ) were reduced in 8/16 readers , equal in 5/16 , and increased in only 3/16 . Conclusion This study broadly confirms previous data showing equivalence of DBT to AV . However , bias against TS may have occurred since the region of interest was not indicated in the TS set as compared to its obvious identification on the AV set by the selected spot views . A key finding is that reader experience with DBT may be more important than so far reported PURPOSE To compare the diagnostic performance of two-dimensional ( 2D ) mammography , 2D mammography plus digital breast tomo synthesis ( DBT ) , and synthetic 2D mammography plus DBT in depicting malignant radiographic features . MATERIAL S AND METHODS In this multicenter , multireader , retrospective reading study ( the TOMMY trial ) , after written informed consent was obtained , 8869 women ( age range , 29 - 85 years ; mean , 56 years ) were recruited from July 2011 to March 2013 in an ethically approved study . From these women , a reading data set of 7060 cases was r and omly allocated for independent blinded review of ( a ) 2D mammography images , ( b ) 2D mammography plus DBT images , and ( c ) synthetic 2D mammography plus DBT images . Review ers had no access to results of previous examinations . Overall sensitivities and specificities were calculated for younger women and those with dense breasts . RESULTS Overall sensitivity was 87 % for 2D mammography , 89 % for 2D mammography plus DBT , and 88 % for synthetic 2D mammography plus DBT . The addition of DBT was associated with a 34 % increase in the odds of depicting cancer ( odds ratio [ OR ] = 1.34 , P = .06 ) ; however , this level did not achieve significance . For patients aged 50 - 59 years old , sensitivity was significantly higher ( P = .01 ) for 2D mammography plus DBT than it was for 2D mammography . For those with breast density of 50 % or more , sensitivity was 86 % for 2D mammography compared with 93 % for 2D mammography plus DBT ( P = .03 ) . Specificity was 57 % for 2D mammography , 70 % for 2D mammography plus DBT , and 72 % for synthetic 2D mammography plusmDBT . Specificity was significantly higher than 2D mammography ( P < .001 in both cases ) and was observed for all subgroups ( P < .001 for all cases ) . CONCLUSION The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups . The use of synthetic 2D DBT demonstrated performance similar to that of st and ard 2D mammography with DBT . DBT is of potential benefit to screening programs , particularly in younger women with dense breasts . ( © ) RSNA , 2015 BACKGROUND Screening for breast cancer with mammography in women aged 50 years or more has been shown to reduce mortality from breast cancer . However , the extent to which mammography contributes to the reduction of mortality in women who also undergo physical examination of the breasts is not known . This study was design ed to compare breast cancer mortality following annual screening consisting of two-view mammography and physical examination of the breasts with mortality following annual screening by physical examination only . Breast self-examination was taught to all participants . METHODS This trial r and omly and individually assigned 39 405 women aged 50 - 59 years , recruited from January 1980 through March 1985 , to one of the study arms . The women were followed by record linkage with the Canadian National Cancer Registry and National Mortality Data base to December 31 , 1993 , and by active follow-up of breast cancer patients to June 30 , 1996 . RESULTS R and omization achieved virtually equal distribution of demographic and breast cancer risk variables . At the first annual screen , 21 % of the cancers found by mammography alone ( in the mammography plus physical examination group ) were 20 mm or more in size compared with 46 % of those found by physical examination in the mammography plus physical examination group and 56 % in the physical examination-only group . The corresponding percentages for screens 2 - 5 were 10 % , 42 % , and 50 % , respectively . Screening detected 267 invasive breast cancers in the mammography plus physical examination group compared with 148 in the physical examination-only group . By December 31 , 1993 , 622 invasive and 71 in situ breast carcinomas were ascertained in the mammography plus physical examination group , and 610 and 16 were ascertained in the physical examination-only group . At 13-year follow-up , with 107 and 105 deaths from breast cancer in the respective groups , the cumulative rate ratio was 1.02 ( 95 % confidence interval = 0.78 - 1.33 ) . CONCLUSION In women aged 50 - 59 years , the addition of annual mammography screening to physical examination has no impact on breast cancer mortality BACKGROUND Mammography is the only proven method for breast cancer screening that reduces mortality , although it is inaccurate in young women or women with dense breasts . We investigated the efficacy of adjunctive ultrasonography . METHODS Between July , 2007 , and March , 2011 , we enrolled asymptomatic women aged 40 - 49 years at 42 study sites in 23 prefectures into the Japan Strategic Anti-cancer R and omized Trial ( J-START ) . Eligible women had no history of any cancer in the previous 5 years and were expected to live for more than 5 years . R and omisation was done central ly by the Japan Clinical Research Support Unit . Participants were r and omly assigned in 1:1 ratio to undergo mammography and ultrasonography ( intervention group ) or mammography alone ( control group ) twice in 2 years . The primary outcome was sensitivity , specificity , cancer detection rate , and stage distribution at the first round of screening . Analysis was by intention to treat . This study is registered , number UMIN000000757 . FINDINGS Of 72,998 women enrolled , 36,859 were assigned to the intervention group and 36,139 to the control group . Sensitivity was significantly higher in the intervention group than in the control group ( 91·1 % , 95 % CI 87·2 - 95·0 vs 77·0 % , 70·3 - 83·7 ; p=0·0004 ) , whereas specificity was significantly lower ( 87·7 % , 87·3 - 88·0 vs 91·4 % , 91·1 - 91·7 ; p<0·0001 ) . More cancers were detected in the intervention group than in the control group ( 184 [ 0·50 % ] vs 117 [ 0·32 % ] , p=0·0003 ) and were more frequently stage 0 and I ( 144 [ 71·3 % ] vs 79 [ 52·0 % ] , p=0·0194 ) . 18 ( 0·05 % ) interval cancers were detected in the intervention group compared with 35 ( 0·10 % ) in the control group ( p=0·034 ) . INTERPRETATION Adjunctive ultrasonography  increases sensitivity and detection rate of early cancers . FUNDING Ministry of Health , Labour and Welfare of Japan Purpose To compare digital mammography ( DM ) plus digital breast tomo synthesis ( DBT ) versus DM alone for breast cancer screening in the Reggio Emilia Tomo synthesis trial , a two-arm test- and -treat r and omized controlled trial . Material s and Methods For this trial , eligible women ( 45 - 70 years old ) who previously participated in the Reggio Emilia screening program were invited for mammography .  Consenting women were r and omly assigned 1:1 to undergo DBT+DM or DM ( both of which involved two projections and double reading ) . Women were treated according to the decision at DBT+DM .  Sensitivity , recall rate , and positive predictive value ( PPV ) at baseline were determined ; the ratios of these rates for DBT+DM relative to DM alone were determined . Results From March 2014 to March 2016 , 9777 women were recruited to the DM+DBT arm of the study , and 9783 women were recruited to the DM arm ( mean age , 56.2 vs 56.3 years ) .  Recall was 3.5 % in both arms ; detection was 4.5 per 1000 ( 44 of 9783 ) and 8.6 per 1000 ( 83 of 9777 ) , respectively ( + 89 % ; 95 % confidence interval [ CI ] : 31 , 72 ) . PPV of the recall was 13.0 % and 24.1 % , respectively ( P = .0002 ) ; 72 of 80 cancers found in the DBT+DM arm and with complete DBT imaging were positive at least at one DBT-alone reading . The greater detection rate for DM+DBT  was stronger for ductal carcinoma in situ ( + 180 % , 95 % CI : 1 , 665 ) ; it was notable for small and medium invasive cancers , but not for large ones ( + 94 [ 95 % CI : 6 , 254 ] ; + 122 [ 95 % CI : 18 , 316 ] ; -12 [ 95 % CI : -68 , 141 ] ; for invasive cancers < 10 mm , 10 - 19 mm , and ≥ 20 mm , respectively ) .  Conclusion DBT+DM  depicts 90 % more cancers in a population previously screened with DM , with similar recall rates BACKGROUND Digital breast tomo synthesis is an advancement of the mammographic technique , with the potential to increase detection of lesions during breast cancer screening . The main aim of the Malmö Breast Tomo synthesis Screening Trial ( MBTST ) was to investigate the accuracy of one-view digital breast tomo synthesis in population screening compared with st and ard two-view digital mammography . METHODS In this prospect i ve , population -based screening study , of women aged 40 - 74 years invited to attend national breast cancer screening at Skåne University Hospital , Malmö , Sweden , a r and om sample was asked to participate in the trial ( every third woman who was invited to attend regular screening was invited to participate ) . Participants had to be able to speak English or Swedish and were excluded from the study if they were pregnant . Participants underwent screening with two-view digital mammography ( ie , craniocaudal and mediolateral oblique views ) followed by one-view digital breast tomo synthesis with reduced compression in the mediolateral oblique view ( with a wide tomo synthesis angle of 50 ° ) at one screening visit . Images were read with masked double reading and scoring by two separate reading groups , one for each method , made up of seven radiologists . Any cancer detected with a malignancy probability score of three or higher by any reader in either group was discussed in a consensus meeting of at least two readers , from which the decision of whether or not to recall the woman for further investigation was made . The primary outcome measures were sensitivity and specificity of breast cancer detection . Secondary outcome measures were screening performance measures of cancer detection , recall , and interval cancers ( cancers clinical ly detected between screenings ) , and positive predictive value for screen recalls and negative predictive value of each method . Outcomes were analysed in the per- protocol population . Follow-up of the participants for at least 2 years allowed for identification of interval cancers . This trial is registered with Clinical Trials.gov , number NCT01091545 . FINDINGS Between Jan 27 , 2010 , and Feb 13 , 2015 , of 21 691 women invited , 14 851 ( 68 % ) agreed to participate . Three women withdrew consent during follow-up and were excluded from the analyses .  139 breast cancers were detected in 137 ( < 1 % ) of 14 848  women . Sensitivity was higher for digital breast tomo synthesis than for digital mammography ( 81·1 % , 95 % CI 74·2 - 86·9 , vs 60·4 % , 52·3 - 68·0 ) and specificity was slightly lower for digital breast tomo synthesis than was for digital mammography ( 97·2 % , 95 % CI 97·0 - 97·5 , vs 98·1 % , 97·9 - 98·3 ) . The proportion of cancers detected was significantly higher with digital breast tomo synthesis than with digital mammography ( 8·7 cancers per 1000 women screened , 95 % CI 7·3 - 10·3 vs 6·5 cancers per 1000 screened , 5·2 - 7·9 ; p<0·0001 ) . The proportion of women recalled after discussion was higher among cancers detected by digital breast tomo synthesis than for those detected by digital mammography after consensus ( 3·6 % , 95 % CI 3·3 - 3·9 vs 2·5 % , 2·2 - 2·8 ; p<0·0001 ) . The positive predictive value for screen recalls was 24·1 % ( 95 % CI 20·5 - 28·0 ) for digital breast tomo synthesis and 25·9 % ( 21·6 - 30·7 ) for digital mammography , and the negative predictive value was 99·8 % ( 99·7 - 99·9 ) and 99·6 % ( 99·4 - 99·7 ) , respectively . The proportion of women who developed interval cancers after trial screening was 1·48 cancers per 1000 women screened ( 95 % CI 0·93 - 2·24 ) . INTERPRETATION Breast cancer screening by use of one-view digital breast tomo synthesis with a reduced compression force has higher sensitivity at a slightly lower specificity for breast cancer detection compared with two-view digital mammography and has the potential to reduce the radiation dose and screen-reading burden required by two-view digital breast tomo synthesis with two-view digital mammography . FUNDING The Swedish Cancer Society , The Swedish Research Council , The Breast Cancer Foundation , The Swedish Medical Society , The Crafoord Foundation , The Gunnar Nilsson Cancer Foundation , The Skåne University Hospital Foundation , Governmental funding for clinical research , The South Swedish Health Care Region , The Malmö Hospital Cancer Foundation and The Cancer Foundation at the Department of Oncology , Skåne University Hospital Breast cancer is the most common cancer type in women and the fourth leading cause of cancer death in the United States ( 1 ) . The goal of screening is to reduce morbidity and mortality , both specific to breast cancer and overall , with acceptable tradeoffs ( 2 , 3 ) . The most commonly used screening test is mammography . Recommended strategies vary for breast cancer screening in average-risk women . Ages to start and discontinue mammography , screening intervals , the role of imaging methods other than mammography , and the role of clinical breast examination ( CBE ) have been points of disagreement among guideline developers . Purpose and Target Population The goal of this American College of Physicians ( ACP ) guidance statement is to critically review selected guidelines from around the world and their included evidence to assist clinicians in making decisions about breast cancer screening in asymptomatic women with average risk for breast cancer . Included screening methods are CBE and breast imaging ( that is , mammography , ultrasonography , magnetic resonance imaging [ MRI ] , and digital breast tomo synthesis [ DBT ] ) . This guidance statement does not address breast self-examination because no evaluated guideline recommends it for screening . The target population for this guidance statement is women with average risk for breast cancer . The target audience is all clinicians . Age is the single most important risk factor for breast cancer . Included guidelines generally define average-risk women as those who do not have a personal history of breast cancer or a previous diagnosis of a high-risk breast lesion , are not at high risk for breast cancer due to genetic mutations known to increase that risk ( such as BRCA1/2 gene mutation or another familial breast cancer syndrome ) , and were not exposed to radiation therapy to the chest in childhood ( 4 , 5 ) . However , definitions of average risk vary among guidelines . In addition , although risk factors ( including early menarche , late menopausal onset , oral contraceptive or menopausal hormone therapy , increased breast density on mammography , and a family member with a history of postmenopausal breast cancer ) may put a woman at greater risk for breast cancer than women without these factors , the evaluated guidelines generally include women with these factors under the umbrella of average risk . Therefore , our guidance statement applies to these women . Guidelines vary somewhat in target population s and screening methods addressed ( Table [ 411 ] and Appendix ) . Both the U.S. Preventive Services Task Force ( USPSTF ) and the World Health Organization ( WHO ) include women with dense breasts and those with a single family member with breast cancer in their guideline 's target population ( 5 , 6 ) . The Canadian Task Force on Preventive Health Care ( CTFPHC ) guideline also includes women with dense breasts ; however , it explicitly mentions that women with a first-degree relative with breast cancer are considered to be at increased risk and are thus excluded from the guideline ( 7 ) . Table . Summary of Included Recommendations in Assessed Guidelines for Breast Cancer Screening of Average-Risk Women Methods The ACP Clinical Guidelines Committee develops guidance statements on topics where several conflicting guidelines are available . Guidance statements rely on evidence presented or referenced in selected guidelines and accompanying evidence reports ; they do not include de novo review s or search es of the literature outside the body of evidence referenced by the guidelines . The goal of ACP guidance statements is to provide clinicians with a rigorous review of the available guidelines and their included evidence and to develop subsequent guidance based on an assessment of the benefits and harms reported by each guideline and its evidence . Unlike ACP guidelines , guidance statements are not derived from a systematic evidence review and hence do not use GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) ( 12 ) to assess the quality of evidence or strength of recommendations . Data Sources and Guideline Selection We search ed the National Guideline Clearinghouse and the Guidelines International Network library for breast cancer screening guidelines from national organizations that addressed breast imaging ( that is , mammography , ultrasonography , MRI , or DBT ) and CBE in women and were published in English between 1 January 2013 and 15 November 2017 . We search ed Web sites housing the selected guidelines for up date s on 10 December 2018 . We excluded guidelines that addressed specific population s ( such as pregnant women and women at increased risk for breast cancer ) or were more than 5 years old ( thus considered inactive ) . We also excluded guidelines that directly endorsed another guideline , such as that of the American Academy of Family Physicians , which endorsed the USPSTF guideline . Our search yielded 3 guidelines , from the American College of Radiology ( published in 2017 ; literature search end date , February 2016 ) ( 9 ) , American Cancer Society ( ACS ) ( published in 2015 ; literature search end date , March 2014 ) ( 4 ) , and USPSTF ( published in 2016 ; literature search end date , June 2015 ) ( 5 ) . We also selected 3 guidelines not identified in either data base but commonly used in clinical practice , from the National Comprehensive Cancer Network ( NCCN ) ( published in 2018 ; literature search end date not reported ) ( 10 ) , WHO ( published in 2014 ; literature search end date , December 2012 ) ( 6 ) , and American College of Obstetricians and Gynecologists ( published in 2017 ; literature search end date not applicable ) ( 8) . In addition , we selected the CTFPHC guideline , which was up date d after our initial search ( published in 2018 ; literature search end date , January 2017 ) ( 7 ) . The American College of Obstetricians and Gynecologists guideline was based on guidelines from the ACS , NCCN , and USPSTF and supporting evidence review s. Critical Appraisal Five co authors independently review ed , assessed , and scored each guideline using the AGREE II ( Appraisal of Guidelines for Research and Evaluation II ) instrument ( 13 , 14 ) ( Appendix Table 1 ) . Appendix Table 1 . Scaled AGREE II Domain Scores for Each Guideline and Overall Assessment Clinician Peer Review The guidance statement was peer- review ed through Annals of Internal Medicine and by ACP Regents and Governors , who represent ACP members at the regional and international level . Public Member Review The development process for the guidance statement included participation by public members ( 2 of the Clinical Guidelines Committee and 7 of ACP 's Public Panel ) to share their perspectives , values , and preferences . Critical Appraisal of Evaluated Guidelines The major difference between high- and low-scoring guidelines ( Appendix Table 1 ) was methodology . Guidelines from ACS ( 4 ) , CTFPHC ( 7 ) , USPSTF ( 5 ) , and WHO ( 6 ) scored highest on the AGREE II instrument , whereas those from the American College of Obstetricians and Gynecologists ( 8) , American College of Radiology ( 9 ) , and NCCN ( 10 ) scored lowest . In addition to our review of each guideline , we examined the evidence supporting the 4 that scored highest ( ACS , CTFPHC , USPSTF , and WHO ) . We also considered recommendations for adoption or adaptation from these 4 guidelines when developing our own guidance . Several factors were important in considering guideline quality . The ACS , CTFPHC , USPSTF , and WHO guidelines best articulated benefits , harms , and strength of the evidence and how these link to recommendations . The lower-scoring guidelines often inadequately described how they considered these factors in developing the recommendations , or they relied on lower- quality evidence . The guidelines varied in the studies they reported , weighting of observational or modeling studies relative to r and omized controlled trials ( RCTs ) , and emphasis on relative versus absolute effects . The guidelines rarely addressed the small absolute effect on breast cancer mortality ; the long lead time to any reduction in this mortality , especially in women with estimated life expectancy less than 15 to 20 years ; and the low incidence of breast cancer for women younger than 60 years . Mammography Depending on the guideline , the recommended age to discuss initiating screening is 40 years ( 4 , 5 , 8) and the recommended age to start screening ranges from 40 ( 9 , 10 ) to 45 ( 4 ) to 50 ( 58 ) years . Most guidelines agree to screen average-risk women with  mammography  between ages 50 and 74 years . However , WHO and CTFPHC recommend that screening in women aged 50 to 69 years should include shared decision making because screening is conditional on a woman 's values and preferences . For women aged 70 to 75 years , WHO recommends screening only in the context of both rigorous research and shared decision making . Other areas of disagreement include screening in women aged 40 to 49 years , screening in women aged 75 years or older , and recommended screening intervals ( Table ) . Intervals range from annual ( particularly in women aged 40 to 49 years ) to biennial or triennial . Guidelines from ACS , USPSTF , and WHO conclude that a close balance exists between screening benefits and harms for women in their 40s ( for ACS , 40 to 44 years ) and that decisions are influenced by patient preferences . The WHO guideline suggests population -based screening programs in women aged 40 to 49 years only in the context of rigorous research , monitoring , and evaluation and if shared decision-making strategies are implemented . The CTFPHC conditionally recommends against screening in women aged 40 to 49 years ( without a first-degree family history of breast cancer ) ; however , it states that some women in this age group may wish to be screened and that clinicians should engage in shared decision making with women who express interest ( Appendix ) . Appendix Table 2 summarizes the available data from the 4 guidelines with the highest AGREE II scores ( ACS , CTFPHC , USPSTF , and WHO ) . Appendix Table 2 . Summary of Evidence on Screening In December 2003 , the European Council identified best practice as key for ensuring development of high- quality cancer-screening programs . To support national policies on cancer control , the European Union institutions progressed several initiatives on cancer . The European Commission ( EC ) Initiative on Breast Cancer ( ECIBC ) is the most recent of these projects and the most implementation driven . Within this initiative , the European Guidelines for Breast Cancer Screening and Diagnosis ( in short , European Breast Guidelines ) are being developed ( http://ecibc.jrc.ec.europa.eu/ ) . Guidelines are approaches to generally improve prevention , diagnosis , treatment , and follow-up of diseases , overcoming inappropriate variations by providing recommendations for best care . The new era of guidelines promises recommendations that are based on the best available evidence summarized in systematic review s while providing the necessary flexibility needed to individualize decisions . The best methods for development of practice guidelines have experienced intense elaboration and attention during the past decades ( 17 ) . The impetus for this attention has been the change from expert- or consensus-based to evidence -based health care recommendations . Although this change in terminology should express the shift from un systematic development of guidelines to systematic and trustworthy recommendations , it is often misunderstood and misconstrued as meaning that experts are now meaningless in the process or as if consensus through discussion is a matter of the past . Neither is correct . Experts from various disciplines and consensus as a result of deliberation remain a mainstay of health care guideline development ( 810 ) . These experts are responsible for prioritization of questions that should be addressed in guidelines ; judgments that result from interpretation of evidence , including the rating of the certainty of the available evidence ; and decisions about how the judgments on the different criteria bear on recommendations . What has changed over time in guideline development are the rules , the structure and explicitness of the process , and the guideline product . Indeed , review s of guideline development methodology and how guidelines can be improved have led to more structured and documented processes that allow a reduction of bias and provide balanced views of appropriately composed guideline panels ( 2 , 5 , 6 ) . Core components for trustworthy guideline development ( 13 , 5 , 7 , 11 ) include that guidelines be developed by a knowledgeable , multidisciplinary panel of experts and representatives from key affected groups ; be based on a systematic review of the existing evidence ; consider important patient subgroups and patient preferences as appropriate ; be based on an explicit and transparent process that minimizes distortions , biases , and conflicts of interest ( 12 ) ; provide a clear explanation of the logical relationships between alternative care options and health outcomes and provide ratings of both the quality of evidence and the strength of the recommendations ( 1316 ) ; and be reconsidered and revised as appropriate when important new evidence warrants modifications . In addition , greater transparency in linking the considered research evidence and the recommendations , as well as the requirement of making structured expert judgments , represents a shift in the guideline development paradigm ( 5 , 11 , 1719 ) . At the same time , developing guidelines for a large number of member states and those that aim to adapt the guidelines poses challenges , such as the feasibility of implementing strategies that may exist in some member countries but not others ( for example , organized population -based screening in Italy but not Greece ) . Addressing these challenges requires considerations that extend beyond strictly clinical efforts in guideline development and mastering the many factors that influence recommendations and their implementation . This article describes the rationale , methods , and processes the ECIBC has adopted to develop the European Breast Guidelines in the context of evolving international st and ards . It also describes an innovative approach to presenting , disseminating , and accelerating implementation of recommendations . Guideline Methodology and Development To adhere to the core requirements for guideline development , the EC has taken several steps . First , it selected , via an open call ( https://ecibc.jrc.ec.europa.eu/ guidelines -team ) , a panel with broad representation of expertise , knowledge , and background , which includes patients , health care professionals , epidemiologists , guideline method ologists , and others ( Appendix ) . These individuals voluntarily participate in the ECIBC and compose the guidelines development group ( GDG ) . Second , it ensured that all recommendations were supported by systematic review s of the evidence conducted by independent scientists from Cochrane Iberoamricathe systematic review team (SRT)following st and ard Cochrane Collaboration methods ( 20 , 21 ) . Third , because this is a women-centered initiative , we included women advocates in the GDG as full voting guideline group members . We separately considered important subgroups of women during recommendation development ( for example , different age groups ) , and we specifically focused on evidence that supports best ways of communicating this information to women to inform their decisions . Fourth , we applied EC conflict of interest rules ( http://ecibc.jrc.ec.europa.eu/rules ) , which are consistent with international recommendations , and used GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) Evidence to Decision ( EtD ) frameworks to minimize the influence of competing interests on the recommendations ( 12 , 17 , 18 ) . These EtD frameworks help guideline panels use evidence in a structured , transparent way to inform decisions with a series of criteria , such as anticipated harms and benefits of the options considered , the certainty of the evidence for those effects , and the costs and feasibility of the options , to help them reach their decision . Fifth , using the GRADE approach to guideline development and its EtD frameworks , we focused our questions and recommendations on outcomes that matter to women and provided a rating of the certainty or quality of evidence and the strength of recommendations that is widely accepted as the reference st and ard ( Figures 1 and 2 ) . Sixth , our evidence review s are up to date when the recommendations are formulated , and we engage in international stakeholder feedback to ensure that recommendations remain timely and relevant to public health and clinical practice . The ECIBC is committed to review ing and updating the recommendations as required when new evidence becomes available . The general process is explained in Figure 3 and is based on the Guidelines International NetworkMcMaster Guideline Development Checklist ( https://hei grade .mcmaster.ca/ guideline -development/using-checklist ) ( 5 ) . Figure 1 . According to GRADE , certainty , quality , strength of evidence , or confidence in the estimate of effect is determined on the basis of a systematic review of the evidence for each outcome ( based on the domains risk of bias , indirectness , imprecision , inconsistency , and publication bias that lower certainty and , usually only for nonr and omized studies , large effects , doseresponse relations and opposing plausible residual confounding that may increase the certainty ) . For recommendations , the overall certainty is determined across outcomes based on the lowest certainty outcome among those critical for decision making for the specific context . The guidelines development group applies the GRADE Evidence -to-Decision frameworks to make recommendations that are made available on the European Commission Web site . ( Reproduced from reference 15 , with permission from Schnemann HJ . ) . GRADE = Grading of Recommendations Assessment , Development and Evaluation . Figure 2 . GRADE EtD frameworks . The GRADE EtD frameworks as available in the GRADE pro software ( www . grade pro.org ) . They help with structuring the entire guideline process into 4 sections and support the conduct of guideline group meetings , presentation , and implementation . They clarify the perspective that is taken by the guideline panel or decision maker and the type of question that is asked in the question section . The section on assessment includes the criteria if the problem is a priority , the balance of health benefits and harms , values and preferences related to the outcomes , cost , re sources and cost-effectiveness , equity , acceptability , and feasibility . Conclusions provide the decision or recommendation with a justification and implementation , as well as research considerations . The presentation function supports the conduct of guideline group meetings and facilitates the output of EtD frameworks to other implementation tools , such as Web sites , h and -held apps , and interactive decision aids . EtD = Evidence to Decision ; GRADE = Grading of Recommendations Assessment , Development and Evaluation ; HTA = health technology assessment ; PICO = population , intervention , comparators , and outcomes . Figure 3 . Approach to guideline development used by the European Commission Initiative on Breast Cancer . The European Commission JRC has oversight of the organization , budgeting , planning , and training . The JRC also manages conflicts of interest , documents all aspects of the work , and manages the membership and group processes . The guideline development group and JRC formulate the questions and work with the systematic review team on identifying and assessing the evidence . The guidelines development group is responsible for developing the recommendations . The JRC is responsible for most other aspects as described in the figure under dissemination , implementation , and updating . JRC = Joint Research Centre ; PICO = population , intervention , comparator , and outcomes . ( Reproduced with adaptation to the JRC process from IMPORTANCE Controversy exists about the frequency women should undergo screening mammography and whether screening interval should vary according to risk factors beyond age . OBJECTIVE To compare the benefits and harms of screening mammography frequencies according to age , breast density , and postmenopausal hormone therapy ( HT ) use . DESIGN Prospect i ve cohort . SETTING Data collected January 1994 to December 2008 from mammography facilities in community practice that participate in the Breast Cancer Surveillance Consortium ( BCSC ) mammography registries . PARTICIPANTS Data were collected prospect ively on 11,474 women with breast cancer and 922,624 without breast cancer who underwent mammography at facilities that participate in the BCSC . MAIN OUTCOMES AND MEASURES We used logistic regression to calculate the odds of advanced stage ( IIb , III , or IV ) and large tumors ( > 20 mm in diameter ) and 10-year cumulative probability of a false-positive mammography result by screening frequency , age , breast density , and HT use . The main predictor was screening mammography interval . RESULTS Mammography biennially vs annually for women aged 50 to 74 years does not increase risk of tumors with advanced stage or large size regardless of women 's breast density or HT use . Among women aged 40 to 49 years with extremely dense breasts , biennial mammography vs annual is associated with increased risk of advanced-stage cancer ( odds ratio [ OR ] , 1.89 ; 95 % CI , 1.06 - 3.39 ) and large tumors ( OR , 2.39 ; 95 % CI , 1.37 - 4.18 ) . Cumulative probability of a false-positive mammography result was high among women undergoing annual mammography with extremely dense breasts who were either aged 40 to 49 years ( 65.5 % ) or used estrogen plus progestogen ( 65.8 % ) and was lower among women aged 50 to 74 years who underwent biennial or triennial mammography with scattered fibrogl and ular densities ( 30.7 % and 21.9 % , respectively ) or fatty breasts ( 17.4 % and 12.1 % , respectively ) . CONCLUSIONS AND RELEVANCE Women aged 50 to 74 years , even those with high breast density or HT use , who undergo biennial screening mammography have similar risk of advanced-stage disease and lower cumulative risk of false-positive results than those who undergo annual mammography . When deciding whether to undergo mammography , women aged 40 to 49 years who have extremely dense breasts should be informed that annual mammography may minimize their risk of advanced-stage disease but the cumulative risk of false-positive results is high Editors ' Notes Context Many states have enacted laws that require mammography facilities to advise women with dense breasts and a negative mammography to consider supplemental testing with their providers . Contribution Three vali date d microsimulation models compared breast cancer outcomes , quality -adjusted life-years gained , and costs for mammography alone versus supplemental ultrasonography after a negative mammography result for women with dense breasts aged 50 to 74 years . Caution Other imaging methods , such as digital breast tomo synthesis , were not assessed . Implication Supplemental ultrasonography screening for women with dense breasts would result in limited health gains and substantially increase costs . Mammographic breast density is a risk factor for breast cancer ( 1 , 2 ) . It also affects mammography performance ( 36 ) . The false-negative rate of screening mammography varies as much as 10-fold from the lowest to the highest categories of breast density ( 5 ) . Because breast density affects cancer risk and the false-negative rate of screening , at least 19 states have enacted legislation requiring that women with dense breasts be told about their breast density after screening mammography and that they should discuss supplemental screening tests , such as ultrasonography , with their providers ( 7 , 8) . Similar legislation is under consideration at the national level ( 9 ) . Breast density notification laws have an uncertain effect on health but could affect millions of women . More than 40 % of women aged 40 to 74 years have dense breasts ( 10 ) , defined in the laws as heterogeneously or extremely dense breast tissue by the American College of Radiology 's Breast Imaging Reporting and Data System ( BI-RADS ) ( 9 , 11 ) . However , the American College of Radiology and other organizations have caution ed legislators , health policymakers , and health care providers to carefully consider the unintended consequences of legislation about breast density notification , including the uncertain harms and benefits of supplemental screening ( 8 , 1215 ) . These concerns are amplified because of the subjective nature of the BI-RADS breast density assessment and the challenges that providers face in accurately assessing and communicating breast cancer risk to their patients . Ultrasonography is often suggested for supplemental screening of women with dense breasts because it is widely available and has relatively low direct medical costs ( 1618 ) . Shortly after Connecticut became the first state to enact a law about breast density notification , as many as 30 % of women with dense breasts at some practice s within the state were having supplemental ultrasonography screening ( 1921 ) . Limited data from clinical trials and observational studies suggest that the addition of h and held ultrasonography screening to mammography for women with dense breasts increases cancer detection rates at the expense of increased biopsies for women without cancer ( 16 , 1922 ) . Moreover , the effect of supplemental ultrasonography screening on long-term outcomes , such as breast cancer mortality and its cost-effectiveness at a population level , are unknown ( 8) . We assessed the potential benefits , harms , and cost-effectiveness of supplemental screening ultrasonography for women with dense breasts using 3 established Cancer Intervention and Surveillance Modeling Network breast cancer models ( 23 ) . The models incorporate evidence from clinical trials and observational studies to estimate the effect of various screening scenarios on breast cancer outcomes , including breast cancer mortality , quality -adjusted life-years ( QALYs ) , and costs ( 24 , 25 ) . The results provide evidence for policymakers considering legislation about breast density notification and for women and providers evaluating screening options for women with dense breasts . Methods We used 3 microsimulation models  developed independently within the National Cancer Institutefunded Cancer Intervention and Surveillance Modeling Network consortium ( www.cisnet.cancer.gov ) : Model E ( Erasmus University Medical Center , Rotterdam , the Netherl and s ) , model G-E ( Georgetown University Medical Center , Washington , DC , and Albert Einstein College of Medicine , Bronx , New York ) , and model W ( University of Wisconsin , Madison , Wisconsin , and Harvard Medical School , Boston , Massachusetts ) . These modeling groups collaborate in the program project grant that supported this study and are described at http://cisnet.cancer.gov/breast/profiles.html and elsewhere ( 2628 ) . Appendix Table 1 outlines the main model differences and assumptions . Our analyses used a lifetime horizon and federal payer perspective . In brief , the models simulated life histories of women who were at risk for breast cancer , had screening , were treated for breast cancer diagnosed by screening or clinical detection , and were at risk for dying of breast cancer and other causes . The models had independent approaches and modeling structures ( 23 ) but used common inputs , including incidence in the absence of screening , mammography performance , treatment effectiveness , and competing causes of death ( 29 ) . The models approximately replicated U.S. breast cancer incidence and mortality trends ( 2628 , 30 ) ( Appendix Figure ) . For this analysis , we used simulated cohorts of women born in 1960 , as described elsewhere ( 24 , 25 ) . Appendix Table 1 . Key Assumptions and Features in the 3 Simulation Models Appendix Figure . Model replication of U.S. incidence and mortality patterns for women aged 30 to 79 y during 19752000 . Model E = Erasmus University Medical Center , Rotterdam , the Netherl and s ; model G-E = Georgetown University Medical Center , Washington , DC , and Albert Einstein College of Medicine , Bronx , New York ; model W = University of Wisconsin , Madison , Wisconsin , and Harvard Medical School , Boston , Massachusetts ; SEER = Surveillance , Epidemiology , and End Results Program . Model Variables At age 40 years , women in the simulated model cohorts were assigned an initial breast density on the basis of the distribution of BI-RADS density categories for premenopausal women in the Breast Cancer Surveillance Consortium ( BCSC ) ( Table 1 ) ( 31 ) . At age 50 years , women were assigned to the same breast density category or the next lower category so the prevalence of breast density categories matched the BCSC observed prevalence for postmenopausal women ( 31 ) . Sensitivity analyses were conducted with model W to examine the effect of reassigning density at both ages 50 and 65 years , on the basis of the BCSC data on the prevalence of breast density for women aged 50 to 64 years ( 44 % with dense breasts ) and 65 years or older ( 33 % with dense breasts ) . In all scenarios , a woman 's modeled risk for breast cancer depended on her age and breast density , on the basis of BCSC data ( Table 1 ) . Table 1 . Key Common Input Used by the 3 Simulation Models : BI-RADS Breast Density Sensitivity and specificity of digital mammography  were determined as a function of age , breast density , and screening interval using BCSC data ( Appendix Table 2 ) ( 32 ) . To our knowledge , the American College of Radiology Imaging Network Protocol 6666 study , a r and omized trial of using h and held ultrasonography to screen women with at least 1 risk factor for breast cancer , was the only controlled study of ultrasonography test performance ( 33 ) . On the basis of this study , experts estimated  screening ultrasonography performance after a negative mammography result for average-risk women . We used a  screening ultrasonography sensitivity of 55 % for women with dense breasts after a negative mammography result . We used a specificity of 94 % , with positive examination results defined as those recommended for biopsy . Models were calibrated so 94 % of ultrasonography screendetected cancer cases were invasive and 6 % were in situ , as seen in published studies ( 16 , 22 ) . Sensitivity analyses evaluated a range of performance characteristics ( Table 2 ) . Appendix Table 2 .  Digital Mammography Sensitivity and Specificity , by Screening Interval , Age Group , and Breast Density Table 2 . Key Common Input Used by the 3 Simulation Models : Screening Ultrasonography Performance Health-related quality -of-life utilities were a function of age ( 34 ) and decremented for breast cancer diagnosis and stage-specific treatment ( 35 ) . Sensitivity analyses included short-term reductions in quality of life for a screening examination ( 0.6 % for 1 week per screening examination ) or a positive screening result ( 10.5 % for 5 weeks ) ( 36 ) . The cost of a digital mammography screen  was $ 138 based on the 2013 Medicare reimbursement rate . Screening ultrasonography does not currently have a specific reimbursement rate , so we used the reimbursement rate for diagnostic breast ultrasonography , which is $ 100 . Sensitivity analyses were also conducted using higher potential reimbursement rates for screening ultrasonography because of its increased work intensity compared with diagnostic ultrasonography .  Diagnostic costs for additional imaging and biopsy after a positive screening mammography result and costs for cancer treatment were based on Medicare reimbursement rates , utilization patterns seen in the BCSC , and estimates from the literature ( 32 , 37 ) . Diagnostic costs after a positive ultrasonography result were assumed to be equal to the biopsy-related costs of diagnostic work-up after a positive mammography result . All costs were in 2013 U.S. dollars . Screening Strategies Primary analysis compared 3 strategies for women aged 50 to 74 years receiving biennial mammography screening  : mammography alone , mammography plus screening ultrasonography after a negative mammography result for women with extremely dense breasts , and mammography plus h and held screening ultrasonography after a negative mammography result for women with heterogeneously or extremely dense breasts ( base case ) . Secondary analyses evaluated the 3 strategies as an annual screening regimen for women aged 40 to 74 years . All strategies were compared with no
target: For example , mammography screening does not seem to create anxiety in women who are given a clear result after a mammogram .
  The incidence of breast cancer and mortality increases with age , and the GDG extrapolated that the absolute health benefits are greater in women aged 45 to 49 than those aged 40 to 44 years .
  However , for the 45- to 49-year age group , the higher breast cancer incidence and mortality compared with women between the ages of 40 and 44 , as well as observational evidence showing a greater benefit in this age group ( 33 ) , led the GDG to judge that the balance of health effects probably favors screening , although the required re sources for screening likely differ across setting s ( 34 , 35 ) .
  Other EtD criteria also were generally in favor of implementing organized mammography screening in this age group .
background: Despite intensified efforts by the European Council since 2003 , the implementation of organized , population -based mammography screening is not uniform across Europe and depends greatly on the policies in place in different countries , the organization of health care , and available re sources ( 1 ) .
  Since the last edition of the European Guidelines on Breast Cancer Screening and Diagnosis was published in 2006 ( 2 ) , new evidence regarding breast cancer and innovation in guideline methodology prompted the European Commission Initiative on Breast Cancer ( ECIBC ) to develop new evidence -based recommendations ( in short , the European Breast Guidelines ) .
  These guidelines inform women , health professionals , and policymakers about important questions related to organized mammography screening and breast cancer diagnosis , but recommendations may apply in context s in which organized screening programs are not in place .
  Women generally consider these undesirable effects acceptable ( low certainty of evidence ) , and a systematic review suggested that women place a relatively low value on the psychosocial and physical effects of false-positive results and overdiagnosis ; however , some studies raised concerns about whether women fully underst and the result ing implication s ( 15 ) .
  How Often Should Women Attend an Organized Mammography Screening Program ?