Search

Purpose: We compared detection measures for breast screening strategies comprising single-reading or double-reading using standard 2D-mammography or 2D/3D-mammography, based on the 'screening with tomosynthesis or standard mammography' (STORM) trial., Methods: STORM prospectively 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., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: We investigated the effect of integrating three-dimensional (3D)-mammography with 2D-mammography on radiologists' detection measures in the 'screening with tomosynthesis or standard mammography' (STORM) trial., Methods: STORM, a prospective population-based trial (Trento and Verona breast screening services) compared sequential screen-reading: 2D-mammography alone and integrated 2D/3D-mammography. Radiologist-specific detection measures were calculated for each screen-reading phase for eight radiologists: number of detected cancers, proportion of true-positive (TP) detection, and number and rate of false-positive (FP) recalls (FPR). We estimated the incremental cancer detection rate (CDR)., Results: There were 59 cancers and 395 false recalls amongst 7292 screening participants. At 2D-mammography screening, radiologist-specific TP detection ranged between 38% and 83% (median 63%; mean 60% and sd 15.4%); at integrated 2D/3D-mammography, TP detection ranged between 78% and 93% (median 87%; mean 87% and sd 5.2%). For all but one radiologist, 2D/3D-mammography improved breast cancer detection (relative to 2D-mammography) ranging between 0% and 54% (median 29%; mean 27% and sd 16.2%) increase in the proportion of detected cancers. Incremental CDR attributable to integrating 3D-mammography in screening varied between 0/1000 and 5.3/1000 screens (median 1.8/1000; mean 2.3/1000 and sd 1.6/1000). Radiologist-specific FPR for 2D-mammography ranged between 1.5% and 4.2% (median 3.1%; mean 2.9% and sd 0.87%), and FPR based on the integrated 2D/3D-mammography read ranged between 1.0% and 3.3% (median 2.4%; mean 2.2% and sd 0.72%). Integrated 2D/3D-mammography screening, relative to 2D-mammography, had the effect of reducing FP and increasing TP detection for most radiologists., Conclusion: There was broad variability in radiologist-specific TP detection at 2D-mammography and hence in the additional TP detection and incremental CDR attributable to integrated 2D/3D-mammography; more consistent (less variable) TP-detection estimates were observed for the integrated screen-read. Integrating 3D-mammography with 2D-mammography improves radiologists' screen-reading through improved cancer detection and/or reduced FPR, with most readers achieving both using integrated 2D/3D mammography., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the performance of the first years since the beginning of a mammographic population-based screening program., Materials and Methods: Women aged 49-69 were invited biennially for two-view film-screen mammography and double reading without arbitration was performed. Interval cancers (ICs) from 2001 to 2006 were identified using screening archives, local pathology archives, and hospital discharge records. The proportional incidence of IC was determined considering breast cancers expected without screening. Three offsite radiologists experienced in breast cancer screening blindly evaluated mammograms prior to diagnosis, randomly mixed with negative mammograms (1:2 ratio). Cases unrecalled at review were considered as true ICs, those recalled by only one reviewer as minimal signs, and those recalled by two or three reviewers as missed cancers. T and N stage of the reviewed ICs were evaluated and compared., Results: A total of 86,276 first level mammograms were performed. Mean recall rate was 6.8% at first and 4.6% at repeat screening. We had 476 screen-detected cancers and 145 ICs (10 of them ductal carcinomas in situ). Absolute incidence was 17 per 10,000 screening examinations. Invasive proportional incidence was 19% (44/234) in the first year, 39% (91/234) in the second year, and 29% (135/468) in the two-year interval. Of 145 ICs, 130 (90%) were reviewed mixed with 287 negative controls: 55% (71/130) resulted to be true ICs, 24% (31/130) minimal signs, and 22% (28/130) missed cancers. The rate of ICs diagnosed in the first year interval was 21% (15/71) for true ICs, 46% (13/28) for missed cancers, and 39% (12/31) for minimal signs, with a significant difference of true ICs rate compared to missed cancers rate (p=0.012). A higher rate of T3 and T4 stages was found for missed cancers (18%, 5/28) compared to minimal signs (6%, 2/31) or true ICs (8%, 6/71), while the rate of N2 and N3 stage for both minimal signs (19%, 6/31) or missed cancers (25%, 7/28) was higher than that for true ICs (10%, 7/71), although all these differences were not significant (p ≥ 0.480)., Conclusion: These results showed the possibility to comply with European Community standards in the first years of a screening program implementation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background & Objectives: Three-dimensional (3D)-mammography (tomosynthesis) may improve breast cancer detection. We examined centre-specific effect of integrated 2D/3D mammography based on the STORM (screening with tomosynthesis or standard mammography) trial., Methods: Asymptomatic women who attended population-based screening through Trento and Verona screening centres were recruited into STORM, a prospective comparison of screen-reading in two sequential phases: 2D-mammography only and integrated 2D/3D mammography. Outcomes were the number and rates of detected cancers and of false positive recalls (FPR), and incremental cancer detection rate (CDR). Paired binary data were compared using Mc Nemar's test., Results: Of 33 cancers detected in Trento, 21 were detected at both 2D and 2D/3D screening, 12 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P < 0.001). Of the 26 cancers detected in Verona, 18 were detected at both 2D and 2D/3D screening, 8 cancers were detected only with integrated 2D/3D screening compared with none detected at 2D-only screening (P = 0.008). There were no differences between centres in baseline CDR, and incremental CDR attributable to 3D-mammography was similar for Trento (2.8/1000 screens) and for Verona (2.6/1000 screens). Trento had 239 FPR (5.7% of screens): 103 FPR at both screen-readings, 93 FPR only at 2D-mammography compared with 43 FPR only at 2D/3D-mammography (p < 0.001). Verona had 156 FPR (5.2% of screens): 78 FPR at both screen-readings, 48 FPR only at 2D-mammography compared with 30 FPR only at 2D/3D-mammography (p = 0.054). Estimated reduction in FPR proportion had recall been conditional to 2D/3D-mammography-positivity differed between centres (21.0% versus 11.5%; P = 0.02)., Conclusion: Integrated 2D/3D-mammography significantly increased cancer detection for both screening services; potential reduction in FPR is likely to differ between centres with those experiencing relatively higher FPR most likely to benefit from 2D/3D-mammography screening., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Digital breast tomosynthesis 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 Tomosynthesis OR standard Mammography (STORM) was a prospective 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. Standard 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) resulted 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. Randomised 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., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

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 prospectively 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 standard 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.

Breast radiological density is a determinant of breast cancer risk and of mammography sensitivity and may be used to personalize screening approach. We first analyzed the reproducibility of visual density assessment by eleven experienced radiologists classifying a set of 418 digital mammograms: reproducibility was satisfactory on a four (BI-RADS D1-2-3-4: weighted kappa = 0.694-0.844) and on a two grade (D1-2 vs D3-4: kappa = 0.620-0.851), but subjects classified as with dense breast would range between 25.1 and 50.5% depending on the classifying reader. Breast density was then assessed by computer using the QUANTRA software which provided systematically lower density percentage values as compared to visual classification. In order to predict visual classification results in discriminating dense and non-dense breast subjects on a two grade scale (D3-4 vs, D1-2) the best fitting cut off value observed for QUANTRA was ≤22.0%, which correctly predicted 88.6% of D1-2, 89.8% of D3-4, and 89.0% of total cases. Computer assessed breast density is absolutely reproducible, and thus to be preferred to visual classification. Thus far few studies have addressed the issue of adjusting computer assessed density to reproduce visual classification, and more similar comparative studies are needed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: The authors sought to assess interobserver agreement in classifying mammography density according to quantitative Breast Imaging Reporting and Data System (BI-RADS) criteria., Materials and Methods: Six expert mammography readers were tested on a set of 100 mammograms. Interobserver agreement was determined according to the kappa statistic, adjusting for chance agreement, on a four-category (D1 vs. D2 vs. D3 vs. D4) or two-category (D1-2 vs. D3-4) basis. Agreement with a panel of 12 readers who had been tested on the same set in a previous study was also assessed., Results: The six readers showed good agreement when compared in pairs [agreement on a four-category basis was substantial (kappa=0.60-0.80) for 13 pairs and almost perfect (kappa>0.80) for two pairs); agreement on a two-category basis was substantial for 12 pairs and almost perfect for three pairs) or compared with the panel (on a four-category basis, agreement was substantial for five of six readers and almost perfect for one; on a two-category basis, agreement was substantial for all readers)., Conclusions: In agreement with previous studies, visual classification of mammography density according to BI-RADS quantitative criteria was highly reproducible among readers; nevertheless, attribution to the "dense breast" (BI-RADS D3-4) category, which might be adopted as a determinant of different screening protocols (such as adjunct ultrasonography or yearly interval) varied among readers (range 6-15%). Controlled studies should be performed comparing visual with computer-density category attribution, the latter possibly being a better alternative due to its absolute reproducibility.

Objectives: Surrogate measures of screening performance [e.g. interval cancer (IC) proportional incidence] allow timely monitoring of sensitivity and quality. This study explored measures using large (T2+) breast cancers as potential indicators of screening performance., Methods: The proportional incidence of T2+ cancers (observed/expected cases) in a population-based screening programme (Trento, 2001-2009) was estimated. A parallel review of 'negative' preceding mammograms for screen-detected T2+ and for all ICs, using 'blinded' independent readings and case-mixes (54 T2+, 50 ICs, 170 controls) was also performed., Results: T2+ cancers were observed in 168 screening participants: 48 at first screen, 67 at repeat screening and 53 ICs. The T2+ estimated proportional incidence was 68% (observed/expected = 168/247), corresponding to an estimated 32% reduction in the rate of T2+ cancers in screening participants relative to that expected without screening. Majority review classified 27.8% (15/54) of T2+ and 28% (14/50) of ICs as screening error (P = 0.84), with variable recall rates amongst radiologists (8.8-15.2%)., Conclusions: T2+ review could be integrated as part of quality monitoring and potentially prove more feasible than IC review for some screening services., Key Points: • Interval breast cancers, assumed as screening failures, are monitored to estimate screening performance • Large (T2+) cancers at screening may also represent failed prior screening detection • Analysis of T2+ lesions may be more feasible than assessing interval cancers • Analysis of T2+ cancers is a potential further measure of screening performance.

There is limited evidence on the role of 3D mammography with tomosynthesis in breast screening, although early studies suggest that it may improve specificity. We prospectively evaluated the effect of integrating 3D mammography as a triage to assessment in 158 consecutive recalls to assessment (recalled in standard 2D-mammographic screening) in asymptomatic subjects. Radiologists provided 3D mammography-based opinion as to whether recall/assessment was warranted or unnecessary, and all subjects proceeded to assessment. 3D triage was positive (confirmed the need for assessment) in all 21 subjects with breast cancer (there were no false negatives), and would have avoided recall in 102 of 137 (74.4%) subjects with a negative/benign final outcome in whom 3D triage did not recommend recall. Proportion of true negative 3D triage (as a proxy for potential reduction in recalls) was slightly higher in dense than non-dense breasts, did not differ across age-groups, but was significantly associated with the type of lesion seen on imaging (being highest for distortions, asymmetric densities, and lesions with ill-defined margins). While the simulation design may have over-estimated the potential for 3D mammography triage to reduce recalls, this study clearly demonstrates its capability to improve breast screening specificity and to reduce recall rates. Future studies of 3D mammography should further assess its role as a recall-reducing strategy in screening practice and should include formal cost-analysis.

Purpose: The aim of this study was to assess the performance of the mammography screening programme in Trento Province, Italy, by analysing the interval cancers (IC) observed from 2001 to 2008., Material and Methods: IC were identified by linking screening archives with local cancer registry and pathology archives as well as with hospital discharge records. Proportional incidence was determined according to breast cancers expected in the absence of screening, estimated on the basis of patients/year at risk and age-specific incidence. The review of screening mammograms preceding ICs was performed by an external (three radiologists) and an internal (five radiologists) panel and aimed at assessing the proportion of IC reviewed as screening errors. Results were compared with European Community (EC) recommended standards., Results: IC proportional incidence was 15.90% for the first year (EC standard <30%) and 25.77% for the second year (EC standard <50%) of the interval. At external review, 18.4% of cases were reviewed as screening errors (identified by at least two of three reviewers), whereas at internal review (identified by at least three of five reviewers) it was 17.4% (EC standard <20%). No significant difference was observed between external and internal review (mean recall rate 8.3% vs. 9.0%; mean identification rate 19.7% vs 19.6%)., Conclusions: The study confirms good performance of the mammography screening programme in Trento Province, Italy. Comparable results of external and internal reviews suggest that the latter, no doubt easier to be implemented, might be adopted as a routine procedure to assess this early efficacy indicator.

The potential to avert breast cancer deaths through screening means that efforts continue to identify methods which may enhance early detection. While the role of most new imaging technologies remains in adjunct screening or in the work-up of mammography-detected abnormalities, some of the new breast imaging tests (such as MRI) have roles in screening groups of women defined by increased cancer risk. This paper highlights the evidence and the current role of new breast imaging technologies in screening, focusing on those that have broader application in population screening, including digital mammography, breast ultrasound in women with dense breasts, and computer-aided detection. It highlights that evidence on new imaging in screening comes mostly from non-randomised studies that have quantified test detection capability as adjunct to mammography, or have compared measures of screening performance for new technologies with that of conventional mammography. Two RCTs have provided high-quality evidence on the equivalence of digital and conventional mammography and on outcomes of screen-reading complemented by CAD. Many of these imaging technologies enhance cancer detection but also increase recall and false positives in screening., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To summarize the existing evidence on the proportional incidence and review of interval cancers, as reported by Italian screening programs., Material and Methods: Literature search of published reports on: a) proportional incidence, determined according to breast cancers expected in the absence of screening and estimated on the basis of patients/year at risk and age-specific incidence; and b) review of screening mammograms preceding interval cancers. Results were compared with European Commission recommended standards., Results: Evidence on proportional incidence or review of interval cancers was reported by 37 and 24 local health unit programs, respectively. Compared to European Commission standards, 94% and 87% of programs complied at first interval cancers survey with recommended standards for proportional incidence or screening error rate at review, respectively. Two programs initially below acceptable standards reached satisfactory results at repeat evaluation over time., Conclusions: Although they are a minority (20%) of all local health unit programs, which suggests a possible selection bias, Italian surveys reporting data on the proportional incidence or review of interval cancers show an overall good performance. Interval cancer survey appears feasible in any program and should become a routine procedure within the national quality control system.

Purpose: The purpose of this study was to assess the performance of delayed second reading of screening mammograms when added to real-time reading plus immediate assessment., Material and Methods: The study setting was the mammography screening programme of an Italian Local Health Unit. Recall rate and cancer detection rate at first reading or informed second reading only were assessed in a cohort of 23,629 women aged 50-69 years screened during 2007-2008. Incremental recall rate, incremental cancer detection rate and incremental cost of second reading were determined., Results: Recall rate was 13.0% at first and 2.7% at second reading (incremental recall rate +21.1%). Overall, recalls were more frequent in the younger decade and in the presence of denser breasts. Cancer detection rate was 7.06‰ (n=167) at first and 0.93‰ (n=22) at second reading (incremental cancer detection rate +13.1%). Compared with first reading, second reading detected more cancers depicted as isolated microcalcifications and distortions (40.9% vs. 16.2%, p=0.02) and at a lower stage (stage 0-I 81.8% vs. 69.5%, p=0.34). The cost of adding delayed second reading was + 3.65 per screened individual or 3,926.61 per incremental cancer detected., Conclusions: The study confirms the efficacy of second reading, even as an adjunct to real-time single reading plus immediate assessment. Incremental recall rate is acceptable in view of the incremental cancer detection rate, and both figures are within the range of literature reports on double-reading performance.

Surveillance of interval cancers (IC) provides a measure of breast screening efficacy. Increased breast density is a predictor of breast cancer risk and of the risk of IC in screening. Improving screening sensitivity in women with dense breasts, through adjunct ultrasound (US), may potentially reduce IC; however this has not been proven. We report on first-year IC in a retrospective cohort of 8865 women who had 19,728 screening examinations (2001-2006): women with non-dense (D1-D2) breasts received mammography (M) screening, and women with dense (D3-D4) breasts also received ultrasound. Data linkage with both hospital discharge records and cancer registry databases was used to identify IC. Underlying cancer rates (cancers observed within 1-year from screening) were 6.3/1000 screens in the D1-D2 group and 8.3/1000 screens in the D3-D4 group. Cancer detection rate (CDR) was 5.98/1000 in all screening examinations; in D3-D4 breasts ultrasound had an additional CDR of 4.4/1000 screens. There were 21 first-year IC, an overall interval cancer rate (ICR) of 1.07/1000 negative screens: 0.95/1000 in women < 50 years and 1.16/1000 screens in women ≥ 50 years. ICR by breast density were 1.0/1000 negative screens in D1-D2, and 1.1/1000 negative screens in D3-D4. Interval cancers were early stage (in situ or small invasive) cancers, almost all were node-negative. Screening sensitivity was 83.5% for mammography alone in D1-D2 breasts relative to 86.7% for mammography with ultrasound in D3-D4 breasts. Our study shows that including ultrasound as adjunct screening in women with D3-D4 breasts brings the IC rate to similar levels as IC in non-dense breasts--this suggests that additional cancer detection by ultrasound is likely to improve screening benefit in dense breasts, and supports the implementation of a randomised trial of adjunct ultrasound in women with increased breast tissue density., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: The authors sought to assess the role of arbitration by a third reader of discordant double readings to reduce the rate of recalls to diagnostic assessment., Materials and Methods: A consecutive series of 7,660 double readings of screening examinations were considered. Discordant recalls were arbitrated by an expert reader (negative/positive). Diagnostic assessment was performed irrespective of arbitration results, and its outcome was used as reference standard for the study purpose. Assuming that negative arbitration would deny recall, its impact was assessed in terms of reduced recall rate and reduced cancer detection rate. Cost analysis of introducing arbitration was performed according to these results., Results: Recalls at double reading were 528 (6.8%), of which 230 (43.5%) were concordant and 298 (56.5%) were discordant. The latter underwent arbitration, which was negative in 216 (72.4%) and positive in 82 (27.6%) cases, respectively. Overall, 49 cancers were detected (6.39 ‰ screened, 9.2% recalled): 43 cancers were detected among concordant (5.6 ‰ screened, 18.6% concordant) and six among discordant recalls (0.7 ‰ screened, 2.0% discordant). Six cancers were observed among arbitrated cases: five (6%) in positive and one (4.6 ‰) in negative arbitrations. Negative arbitration would have spared 216 assessment procedures (2.8% absolute, 40.9% relative reduction of recall rate) while missing one cancer case (0.13 ‰ absolute, 2.0% relative reduction of cancer detection rate). Arbitration cost was 74 euro, whereas 216 spared assessment procedures would have cost 14,558.4-23,346 euro., Conclusions: Arbitration is a cost-effective procedure that could be employed as a first measure to counterbalance excess recall rate observed in a double-reading scenario.

We review the accuracy and potential effect of mammography in surveillance of women with a personal history of breast cancer (PHBC). A literature review was performed to identify studies on screening mammography or breast surveillance reporting data on the accuracy or detection capability of mammography, or the effect of early detection of second breast cancers, in women with a PHBC. Evidence on mammography screening in women with PHBC comes from non-randomised studies, and is generally limited by several factors including design limitations. The proportion of ipsilateral breast recurrences detected with mammography ranges between 50% and 80% (including cancers detected also on clinical examination) but is lower at 8%-51% for mammography-only detection. Mammography detects approximately 45%-90% of contralateral cancers. There is evidence of a potential benefit for asymptomatic/early-detected second breast cancers (range of estimated hazard ratios: 0.10-0.86) relative to symptomatic or clinical-detection, in various surveillance strategies that include mammography, however these estimates are likely to have overestimated screening benefit. New evaluations of screening women with a PHBC are needed from screening programs or population datasets, to provide comprehensive measures of screening accuracy and outcomes in this population of women., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (-5.1%) and a lower recall rate (-9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Aims and Background: To analyze stage distribution and biological features of interval cancers observed in Verona mammography screening compared to screen-detected cancers and "clinical" cancers occurring in the absence of screening, as provided by the Veneto Cancer Registry., Methods and Study Design: Screen-detected cancers were identified in the screening archives. Interval cancers and clinical cancers (occurring in women never screened or not yet invited) were identified through the local cancer registry. Studied variables were age, stage, pathological pT and pN category, histological grading, estrogen and progesterone receptor status, and proliferation index (Ki67)., Results: We compared 95 interval cancers, 761 screen-detected cancers, and 1873 clinical cancer cases. Interval cancers had more aggressive features than screen-detected cancers, the difference being statistically significant for pT (P=106), pN (P = 0.0003), grading (P = 0.007), estrogen receptors (P = 0.0006), and progesterone receptors (P = 0.00005), but not for Ki67 (P = 0.18). The features of interval cancers were not more aggressive than those of clinical cancers for pT (P = 0.84), pN (P = 0.33), grading (P = 0.61), estrogen receptors (P = 0.48), and progesterone receptors (P = 0.69), and were better for Ki67 (P = 0.02). In contrast, screen-detected cancers showed significantly better features than clinical cancers, for all studied variables: pT (P = 10(-6)), pN (P = 10(-6)), grading (P = 10(-6)), estrogen receptors (P = 10(-5)), progesterone receptors (P = 10(-6)), and Ki67 (P = 10(-6))., Conclusions: Our findings are consistent with the length biased sampling hypothesis of interval cancers having a faster growth rate and a less favorable presentation than screen-detected cancers. Compared to clinical cancers, interval cancers had similar features, whereas screen-detected cancers had definitely more favorable features. This finding suggests, rather than a faster growth rate for interval cancers, a slower growth rate for screen-detected cancers, which, together with diagnostic anticipation, may explain a certain degree of overdiagnosis.

Purpose: The purpose of this study was to assess the interval cancer (IC) proportional incidence and review IC cases observed in an Italian mammography screening programme during 2000-2006., Materials and Methods: ICs were identified through linkage of a screening database with the local cancer registry and hospital discharge records to calculate proportional (observed/expected) incidence. Negatively reported mammograms preceding ICs underwent blind review (randomly mixed with negative controls in a 2:1 ratio) by three expert radiologists and classified according to European guidelines criteria (OC=occult, MS=minimal sign, SE=screening error) according to majority report. Proportional IC incidence and rate of reviewed IC classified as SE were compared with European guideline standards., Results: Proportional IC incidence was 10.8% in the first and 40.0% in the second year of the interval (European standard=30% or 50%, respectively). Sensitivity estimate for the 2-year interval was 74.6%. ICs were reviewed as SE, MS or OC in 15.0%, 14.0% or 71.0% of cases, respectively. Corresponding review results for negative controls were 7.0%, 25.0% or 68.0%, respectively. Positive predictive value for IC was 51.7% for SE and 21.8% for MS reporting category, respectively (p=0.008). European standard (<20% reviewed as SE) was reached., Conclusions: The study shows that the sensitivity of the mammography programme was good, complying with European guideline recommendations. Assessment of IC-based early indicators of screening efficacy is feasible in a current screening programme and should become a routine procedure.

Purpose: The study compares the diagnostic accuracy (correct identification of cancer) of a new computer-assisted diagnosis (CAD) system (Cyclopus) with two other commercial systems (R2 and CADx)., Materials and Methods: Cyclopus was tested on a set of 120 mammograms on which the two compared commercial systems had been previously tested. The set consisted of mammograms reported as negative, preceding 31 interval cancers reviewed as screening error or minimal sign, and of 89 verified negative controls randomly selected from the same screening database., Results: Cyclopus sensitivity was 74.1% (R2=54.8%; CADx=41.9%) and was higher for interval cancers reviewed as screening error (90.9%; R2=54.5%; CADx=81.8%) compared with those reviewed as minimal sign (65.0%; R2=55.0%; CADx=20.0%). Specificity was 15.7% (R2=29.2%; CADx=17.9%). Overall accuracy was 30.8% (R2=35.8%; CADx=24.1%). The positive predictive value of a case with CAD marks [regions of interest (ROI)] was 23.4% (23/98; R2=16.0%; CADx=15.1%). Average ROI number per view among negative controls was 1.13 (R2=0.93; CADx=0.99). Cyclopus was more sensitive for masses compared with isolated microcalcifications (208 vs 62 ROI; R2=90 vs 213; CADx=192 vs 130)., Conclusions: Compared with two other commercial systems, Cyclopus was more sensitive (R2 p=0.14; CADx p=0.02) and less specific (R2 p=0.02; CADx p=0.64).

We review the evidence on computer-aided detection (CAD) as an adjunct to mammography interpretation, and discuss the complexity of its impact on decision-making and potential medico-legal aspects. CAD prompts the reader to review lesions on the mammogram and re-evaluate the decision on whether to recall CAD-prompted findings. Studies show that CAD can improve the sensitivity of a single reader, with an incremental cancer detection rate (from adding CAD to a single read) ranging between 1 and 19%. However, CAD will also substantially increase the recall rate (decrease the reader's specificity) causing additional recall in approximately 6-35% of women. Evidence indicates that CAD does not perform as well as double (human) reading in the context of organized breast screening where double reading is the standard of care. Although CAD can identify and prompt readers to missed cancers, the high number of false-positive prompts (1.5-4 false prompts per case) can have an adverse effect on clinical decision-making, and detracts from CAD's application in screening practice. Refinement in CAD algorithms, in combination with increasing implementation of digital mammography, may improve the potential use of CAD in mammography reading, but will require prospective evaluation.

Background: Recent evidence suggests that computer-aided detection (CAD) may have a negative impact on the interpretation of mammography-this necessitates timely evaluation of CAD in practice. We report a retrospective study of the incremental effect of CAD on the accuracy of full-field digital mammography (DM) as applied prospectively in breast assessment., Methods: Subjects were all consecutive women attending a self-referral breast centre in Florence between September 2005 and January 2007 (N = 3,425). DM was reported without, then with, CAD according to a standard protocol; all mammograms recalled on the basis of either the radiologist's reading alone, or the radiologist's reading after viewing CAD, were recalled to assessment., Results: Overall recall rate (RR) was 13.1% and 107 cancers were diagnosed (90 invasive cancers, 8 DCIS, 9 malignant on cytology). The use of CAD allowed the additional detection of 5 cancers (three invasive cancers, one DCIS, one malignant on cytology) and caused one additional benign surgical biopsy, with a relative RR of 4.9%, and an incremental RR of 1.17%. The cancer detection rate (CDR) of DM interpreted with the use of CAD was 3.12% and did not significantly differ from the CDR of 2.9% based on DM without CAD (chi(2) = 3.2, P = 0.07)., Conclusion: While the increase in CDR with the use of CAD only approached statistical significance, representing modest gains in absolute terms, the incremental number of cancers detected justifies the incremental recall and benign surgical biopsy attributable to CAD use. In our clinical setting, these data suggest more benefit than harm in using CAD with DM, and we will continue the use of CAD with ongoing monitoring of patient outcomes.

Evaluation of: Badgwell BB, Giordano SH, Duan ZZ et al.: Mammography before diagnosis among women age 80 years and older with breast cancer. J. Clin. Oncol. 26, 5-8 (2008). While strong scientific evidence of efficacy supports the recommendation of mammography screening up to the age of 74 years, the current recommendation of continuing screening up to or beyond the age of 80 years, issued by several guidelines, is not based on controlled evidence of screening efficacy, but simply on the assumption that mammography increases its accuracy with age and that mammography screening must be beneficial, providing that life expectancy is long enough to allow for the benefit to take place. In the present study, a large series of breast cancer patients aged 80 years or above was considered, demonstrating that mammography use is associated with less advanced stage at diagnosis and with better survival. The authors conclude that the opportunity for continuing screening beyond the age of 80 years, owing to its potential benefit, should be discussed with patients, particularly those without significant comorbidity, foretelling a longer life expectancy. Although their findings may also suggest a benefit in terms of mortality reduction, the clear presence of a healthy screening effect, lead time and overdiagnosis considerations call for major caution, since screening might be more detrimental than beneficial.

Surveillance of interval cancers (IC) lacks standardisation of review methodologies. We investigated the extent to which 'informed' or 'blinded' review may affect IC classification. This is a retrospective study of 100 validated screening mammograms (20 IC, 80 negative screens) independently reviewed by six radiologists. Three sequenced review methods with increasing information were used: (1) blinded (no IC information, case mix), (2) partially informed, and (3) fully informed. IC 'screening error' (SE) reports averaged 24% (10-40), 33% (20-55), and 42% (35-50) for phases 1, 2, and 3, while 'minimal signs' (MS) reports averaged 6% (5-15), 10% (10-20), and 20% (15-30), respectively. Negative mammograms classification was MS in 18% (7-39) or SE in 19% (11-29), respectively. MS or SE classification was more likely for method 2 (OR=1.78, p=0.033) and method 3 (OR=3.91, p=0.000) relative to method 1, but no reader effect was evident. Inter-observer agreement in classifying at method 1 was slight (k 0.20), lowest (k 0.06) for MS, and fair (k 0.25) for negative and SE categories. More 'informed' review is more likely to yield an IC classification as MS or SE. Due to expected variability, review methods need standardisation to improve screening quality. Our data support blinded review of IC in mammography screening.

Aim: To assess the role of breast ultrasonography as a complement to negative mammography in radiologically dense breasts., Material and Methods: Out of a total series of 49,044 consecutive mammograms reported as negative in asymptomatic women, 25,665 (52.3%) were coded as dense (BI-RADS D3-4) and ultrasonography was recommended. Due to organizational problems, ultrasonography was performed immediately or within 1 month only in 5,227 cases, representing the study series., Results: Two cancers were detected at immediate ultrasonography (0.03%). The cancer detection rate in women aged 40-49 and 50-69 years was 0.002% and 0.07%, respectively. The benign biopsy rate was 0.5% for core biopsies and 0.02% for surgical biopsies. The cost per ultrasonography-assessed woman was Euro 56.05, whereas the cost per additional mammographically occult but ultrasonography-detected cancer was Euro 146,496.53. The mammograms of the 2 cancer cases underwent blind review by an expert reader and were confirmed as negative., Discussion: Our findings show a low cancer detection rate, substantially lower compared to other clinical studies of ultrasonography in dense breasts, though in accordance with preliminary evidence from an Italian randomized clinical trial within a population-based screening program. The policy of adding ultrasonography to negative mammography in dense breasts seems to have very limited cost-effectiveness, and should not be adopted in routine practice before results of ongoing clinical trials are available.

Objective: The purpose of this study was to compare the diagnostic accuracy of digital mammography with that of screen-film mammography in concurrent cohorts participating in the same population-based screening program., Materials and Methods: In a retrospective study covering 2004-2005, we compared digital with screen-film mammography in two concurrent screening cohorts of women 50-69 years old participating in a screening program operated from mobile units. Each cohort had 14,385 participants matched by age and interpreting radiologist from all participants consecutively registered. We compared recall and cancer detection rates., Results: The recall rate was higher for digital mammography (4.56% vs 3.96%, p = 0.01), particularly when clustered microcalcifications were the only finding (1.05% vs 0.41%, p = 10(-6)) and for younger women (50-59 vs 60-69 years, 5.12% vs 4.17%, p = 0.009). The higher recall rate for digital mammography was mainly evident at incidence screening. The recall rate due to poor technical quality was lower with digital mammography (0.27% vs 0.50%, p = 0.002), possibly because real-time feedback was available. The detection rate was higher for digital mammography (0.72% vs 0.58%, p = 0.14), particularly for cancers depicted as clustered microcalcifications (0.26% vs 0.12%, p = 0.007), in younger (50-59 years) women (0.63% vs 0.42%, p = 0.09), and in denser breasts (1.09% vs 0.53%, p = 0.24). No significant difference was observed in positive predictive value on recall for digital mammography or screen-film mammography. Early cancer (pTis, pT1mic, pT1a) was more frequent in cancer detected with digital mammography than in that detected with screen-film mammography (41.3% vs 27.3%, p = 0.06)., Conclusion: Digital mammography may be more effective than screen-film mammography in contemporary screening practice in mobile units. The data indicate that digital mammography depicts more tumors than does screen-film mammography, especially lesions seen as microcalcifications. The potential association with improved outcome warrants further study.

Aim: We studied imaging, pathology and diagnostic aspects of false negative assessment (FNA) in women recalled for suspicious screening mammography., Method: Subjects were women aged 50-69 years undergoing biennial screening mammography within the Florence District screening programme from January 1992-December 2001 (339,953 consecutive screens). We identified all cancers occurring in women recalled to assessment and ascertained, and reviewed, all cases considered as negative on assessment and subsequently diagnosed with breast cancer. We compared imaging features, tumour histology and stage, and diagnostic testing on assessment for all women with cancer, and presentation and length of delay in women falsely negative on assessment., Results: Eleven thousand six hundred and twenty four women were recalled to diagnostic assessment (recall rate = 3.4%) predominantly for suspicious mammography (9,216 positive screens). Breast cancer was missed in 57 cases: a FNA rate of 0.50% (0.37-0.62%) and comprising 4.1% (3.0-5.1%) of cancers occurring in women recalled after a positive screen. Two types of abnormalities were significantly more frequent in FNA cases than cancers detected at assessment: mass with regular borders (21.1 vs. 5.6%, p = 10(-5)), and asymmetrical density (22.8 vs. 5.4%, p = 10(-5)). On review 56% of FNAs were benign or probably benign BI-RADS categories. FNA occurred in 1.4% of early recalls and in 0.4% of initial assessment (p=0.0001). Significantly fewer tests were performed when assessing missed cancers than detected cancers with the most significant difference noted for FNAC (29.8 vs. 96.0%, p=10(-6)); mammography as the only evaluation on assessment was more frequent in missed cancers (31.5% vs 0.2%, p = 10(-6)). The 57 missed cases were subsequently diagnosed at early recall (2 cases), next biennial screen (11 cases), or as interval breast cancers (44 cases) with a mean delay in diagnosis of 628 days. Tumour histology, size and nodal status did not significantly differ between cancers missed and cancers diagnosed on assessment., Conclusion: False negatives on assessment represent a minority group in whom screening has failed. They might be reduced by adopting a more intensive diagnostic approach to assessment. Although there was no evidence of a worse prognosis in cancers missed at assessment, the delay in diagnosis is substantial and may impact long-term outcomes.

Combining mammography and ultrasound improves the sensitivity of imaging diagnosis. In the context of clinical masses, where percutaneous needle biopsy is routinely incorporated into the diagnostic pathway, little is known about the incremental gain in sensitivity where using single relative to combined imaging. We examined the sensitivity of imaging and needle biopsy combinations in a cohort of 1000 women with clinically evident (clinically presenting and/or clinically palpable) breast cancer. We report the distribution of age, tumour stage and node status, clinical findings, and individual test outcomes in all subjects. Sensitivity--true positive rate for cancer detection--of different test combinations (with the number of cases missed in 1000 subjects given in parentheses) is: mammography and ultrasound 97.9% (21); mammography with needle biopsy 99.5% (5); ultrasound with needle biopsy 99.5% (5); combined imaging with needle biopsy 99.6% (4). Using only one imaging test (irrespective of whether that is mammography or ultrasound) in combination with needle biopsy provides the same sensitivity, with an incremental gain in sensitivity of 0.1% where combined imaging is included into the diagnostic pathway. This is largely due to needle biopsy identifying most cancers missed on single imaging thus negating the effect of additional imaging on overall sensitivity.

The Italian Mammography Screening Network (GISMa) held a national consensus conference in Bologna, May 25-26 2006. The large panel of participants included national experts in fields related to breast cancer and screening issues. The final aim was the production of a consensus statement which might become a standard reference for Italy. The consensus document (http://www.gisma.it) states that full national coverage by organized screening for breast (age 50-69), cervical and colorectal cancer is a priority, before any extension of organized mammography screening to younger or older age groups may be considered. If adequate resources are available, extension of organized screening for breast cancer until age 74 is recommended, at least for regular attenders until age 69. Extension of organized screening to women aged 40-49 may be considered at some conditions: (a) that resources are available, (b) that a 1-year interval is adopted, (c) that proper information of the limitations of screening is given to participants and (d) that priority is given to age 45-49.

Purpose: The aim of this study was to evaluate the performance of a sample of Italian radiologists undergoing a proficiency test of screening mammography., Materials and Methods: We retrospectively analysed the results of 705 tests (537 first tests, 168 repeat tests) taken during 1997-2005 by 537 Italian radiologists. The test, consisting of 17 screen-detected cancer cases and 133 negative controls, was validated by a panel of expert readers defining a minimum standard as to sensitivity for cancer and recall rate of negative controls. Success rates were assessed as a function of previous experience in mammography (years of experience, total mammograms read, mammograms read in the last year)., Results: A total of 176 radiologists successfully passed the test at their first attempt (32.7%). Success correlated with experience, measured in terms of years of experience (5-year cutoff: chi(2) for trend=4.17, p=0.04), total mammograms read (chi(2) for trend =11.8, p=0.002) or mammograms read in the last year (chi(2) for trend=6.27, p=0.04). Training improves performance at repeat testing: after a first negative attempt, a second attempt was successful in 50.6% of cases (74/146) and a third in 68.1% (15/22)., Conclusions: A substantial proportion of Italian radiologists taking the test showed limited proficiency in screening mammography. This finding is consistent with several reports of poor performance of service screening compared with reference standards. As expected, test performance is associated with experience, suggesting that the current policy of employing non-dedicated, untrained, general radiologists in screening should be reconsidered. Test performance improves with training (courses, consultation of teaching atlases). Several screening programmes in Italy have been implemented without prior adequate radiologist training. Radiologist training needs to be considered a priority, at least in those screening programmes that are still to be implemented in one third of the country.

We evaluated the role of computer-aided detection (CAD) in cancers undergoing double reading and detected by one reader only. A series of 33 cancers, originally missed by the first reader and detected by the second reader, and 75 negative controls were processed to assess CAD sensitivity, and was read by the six radiologists who originally missed the cancers with the help of CAD printouts. CAD case-based sensitivity, specificity and positive predictive value were 51.5%, 18.6% and 21.7%, respectively. Average sensitivity of all radiologists in all cancers in the series was 74.7%, being higher for CAD+ (86.2%) than for CAD- (62.5%) cancers (P<0.01). When reading cancer cases that they had originally missed, radiologists had a sensitivity of 75.8%, which was higher for CAD+ (100.0%) than for CAD- (58.3%) cancers. The average recall rate was 14.2%, the majority of recalls (45 out of 64) occurring for lesions marked by CAD. CAD may help in detecting at most half of cancers missed at a single reading but detected by a second reader.

We calculate the positive predictive value (PPV) of abnormal (C3-5) FNAC, alone and in combination with clinical and imaging findings, based on a consecutive series of 2,334 subjects. The PPV of a C3, C4 or C5 report is 55.0%, 95.9% and 99.4%, respectively. C5 Cytology is highly predictive of malignancy (PPV=99.4-99.7%) except where imaging is negative or benign. When C4 cytology is associated with suspicious findings on imaging and/or palpation, its PPV increases to 98.5-98.7%. C3 is the least predictive of malignancy and even when associated with suspicious findings on imaging and/or palpation its PPV is 83.3% - C3 FNAC should therefore prompt pre-operative core biopsy. These data indicate that FNAB is still a useful test in breast diagnosis, and it may assist clinical decision-making as far as whether patients should progress to surgical management or should have further core biopsy before planning surgery.

Purpose: The purpose of this study was to assess the usefulness of routine ultrasonography in women with negative mammography and dense breasts [Breast Imaging Reporting and Data System (BIRADS D3-4)]., Materials and Methods: We applied a protocol involving routine ultrasonography in a consecutive series of subjects with negative mammography and dense breasts. After evaluation by internal and external reviewers of cancers detected by ultrasonography performed to confirm negative mammography, we determined the additional cancer detection rate of ultrasonography and the cost of the protocol., Results: Out of 17,883 total mammographies, 167 cancers were diagnosed (detection rate: 0.93%). Out of 257 suspicious mammographies, 138 cancers were detected. Out of 17,626 negative mammographies, 6,449 (36.5%) were classified as "dense breast" and underwent ultrasonography: 29 cancers were detected (detection rate: 0.44%, or 17.3% of total cancers). Out of 25 cancer cases reviewed, negative mammography and asymptomatic status was confirmed in 15 (detection rate 0.23%, or 8.9% of total cancers). The cancer detection rate was 0.11%, 0.22%, 0.32% and 0.14% for age groups <40, 40-49, 50-59 and >59, respectively. The cost per additional carcinoma detected by ultrasonography alone was euro 25,847.85 whereas that per examined woman was euro 21.68., Conclusions: The study confirms the possibility that ultrasonography can detect mammographically occult breast carcinoma in dense breasts. The evidence is insufficient to recommend this policy in routine screening practice but suggests that, at least in current clinical practice, adding ultrasonography in dense breasts may be useful despite the substantial costs.

Interval breast cancers-those diagnosed after a negative mammographic screen and before the next scheduled screen-are an important indicator of the potential effectiveness of population screening for breast cancer. Although the incidence of interval cancers is usually monitored, radiological surveillance is not undertaken routinely in most screening programmes. Here, we describe radiological surveillance of interval breast cancers and discuss methodological difficulties in the radiological review process and in the categorisation of interval cancers as false-negative, true, or occult. Furthermore, we identify methods that affect whether an interval cancer is classified as a false-negative (missed) or a true interval cancer. For all radiological categories of interval cancers, we outline possible changes to screening programmes that might improve cancer detection. Standardised radiological surveillance of interval cancers might allow within-programme comparisons and has the potential to guide practice and improve quality.

The inter- and intraobserver agreement (K statistic) in reporting according to BI-RADS assessment categories was tested on 12 dedicated breast radiologists, with little prior working knowledge of BI-RADS, reading a set of 50 lesions (29 malignant, 21 benign). Intraobserver agreement (four categories: R2, R3, R4, R5) was fair (0.21-0.40), moderate (0.41-0.60), substantial (0.61-0.80) or almost perfect (>0.80) for one, two, five or four radiologists, or (six categories: R2, R3, R4a, R4b, R4c, R5) fair, moderate, substantial or almost perfect for three, three, three or three radiologists, respectively. Interobserver agreement (four categories) was fair, moderate or substantial for three, six, or three radiologists, or (six categories) slight, fair or moderate for one, six, or five radiologists. Major disagreement occurred for intermediate categories (R3=0.12, R4=0.25, R4a=0.08, R4b=0.07, R4c=0.10). We found insufficient intra- and interobserver consistency of breast radiologists in reporting BI-RADS assessment categories. Although training may improve these results, simpler alternative reporting methods (systems), focused on clinical decision-making, should be explored.

Purpose: The use of full field digital mammography (FFDM) in alternative to conventional screen film mammography (SFM) in the current practice is delayed by the high costs of FFDM. The present study, performed at the Centro per lo Studio e la Prevenzione Oncologica of Florence, using both FFDM and SFM, was aimed at estimating the impact of introducing the new FFDM technique on overall mammography costs., Material and Methods: We estimated the differential costs of both methods, based on real expenditures, as provided by the administrative department, and on radiologists, radiographers and other staff's working time. Two different workload scenarios (5000 and 10,000 tests/year per mammography equipment) were considered. Common costs of both techniques were censored for study purpose., Results: Beside a higher cost due to purchase and hire/leasing costs of equipment, FFDM implies a greater workload for radiologists (reading time almost doubled). SFM implies a greater workload for the administrative staff to run the archive and for loading/unloading films of the roller viewer, whereas no different workload has been observed for radiographers. Overall FFDM costs 24.22-26.46 for examination more than SFM for the 5000 tests scenario and 9.91-12.15 more for the 10,000 tests scenario., Discussion: Although present study estimates cannot easily be generalised to any local setting, the model for cost calculation is easy to be exported to another scenario by applying different local parameters. The advantages made available by FFDM (computerised data recording, tele-transmission, tele-reporting, tele-consulting, automatic display on monitor of previous exams and use of CAD) may justify the higher cost, but a limited reduction in purchase and assistance costs could easily allow a turnover, with FFDM being more convenient than SFM even on the cost side.

Aims and Background: Service mammography screening has been reported to have suboptimal performance compared to controlled trials. The aim of this study was to evaluate the sensitivity of the mammography screening program in four Local Health Units (ASL) and the possible causes of diagnostic error in cases further surfacing as interval cancers., Material and Methods: Interval cancers were identified by cross checking of screened women databases with hospital discharge records reporting breast cancer. Proportional interval cancer incidence (observed interval cancers/expected invasive cancers) was determined by matching the database of women screened during 1999-2002 to the hospital discharge records databases during 1999-2003. The ratio of observed interval cancer rate to underlying incidence was compared to international standards and with literature data. Screening mammograms reported as negative and followed by interval cancers were randomly mixed with true-negative controls, and the resulting set underwent blind review by an external radiologist who applied the conventional criteria recommended for the classification of the type of diagnostic error (occult, minimal signs, screening error)., Results: Matching of screening archives with the hospital discharge records databases allowed for the identification of 154 invasive interval cancers compared to 480 expected. The proportional observed/expected interval cancer incidence in the first and second year of the interval was 21% and 46%, respectively (ASL 1 = 14% or 38%, ASL 2 = 19% or 48%, ASL 3 = 30% or 53%, ASL 4 = 25% or 49%). Radiological review included 38 further interval cancer cases, identified after the time limits defined for proportional interval cancer incidence assessment, and could not include 18 interval cancers, not retrieved from ASL 4 archives: overall, 174 interval cancers were reviewed, of which 135 were classified as occult (77.3%) (ASL 1 = 83.3%, ASL 2 = 71.1%, ASL 3 = 78.6%, ASL 4 = 75%), 12 (6.9%) as minimal signs (ASL 1 = 6.6%, ASL 2 = 11.5%, ASL 3 = 2.4%, ASL 4 = 5%), and 27 (15.5%) as screening error (ASL 1 = 8.3%, ASL 2 = 17.3%, ASL 3 = 19.0%, ASL 4 = 25%)., Conclusions: Observed proportional interval cancer incidence was lower than commonly reported for service screening programs and currently recommended (< 30% in the first, < 50% in the second year of the interval). The analysis of interval cancer causes showed a screening error rate below the maximum acceptable standard (< 20% of interval cancers should be classified as screening error) in three of four programs and in average figures. Substantial differences observed among single programs (one did not comply to recommended standards) suggest that space is available for the improvement of overall performance by optimizing program organization and by further training of radiologists. Overall, the analysis showed a good sensitivity of the screening program in the Veneto Region, although the performance was inferior to that of excellence centers, and further action to improve it is possible. Assessment and review of interval cancers is an early indicator of screening efficacy which has not yet been fully adopted in Italian screening programs. Although using hospital discharge records to identify interval cancers may be affected by limited errors, such a procedure is particularly convenient, as data from hospital discharge records are available much in advance compared to cancer registries and are the most reliable source of information for areas uncovered by a cancer registry. Hospital discharge records-based procedures for interval cancers assessment should be employed routinely in screening programs.

Purpose: To compare the performance of screen-film and digital mammography in the assessment of screen-detected breast lesions., Materials and Methods: A series of 100 consecutive mammographic screen-detected lesions (65 masses, 6 architectural distortions, 29 microcalcifications) deserving diagnostic assessment and judged to have a low positive predictive value underwent screen-film mammography (SFM) and digital mammography by a Fuji computed radiography system (FCR) (double exposure, same view, without removing compression) of the corresponding breast. Three sets of images (SFM, hard copy and soft copy FCR) were read, blind of assessment outcome, by three experienced radiologists. For the three different imaging modalities a contrast-detail analysis, dose evaluation and diagnostic accuracy by means of ROC analysis were performed. At the end of the diagnostic workup all suspicious cases (20) underwent surgical biopsy and were histologically confirmed as cancers and the cases which were negative or benign at assessment (80) were followed up for a period of 12-20 months. During the follow-up period two more cases proved to be cancers at subsequent examinations., Results: Contrast-detail analysis gives better image quality for FCR compared to SFM at the same delivered dose, whilst in ROC analysis the SFM (AUC 0.7158), hard copy FCR (AUC 0.7404) and soft copy FCR (AUC 0.7501) (chi(2)=1.30, p=0.5220) are equivalent., Conclusion: FCR has a diagnostic performance equivalent to SFM in the assessment of screen-detected lesions with a low positive predictive value for cancer and it may be safely included in routine screening practice.

The inter- and intraobserver agreement (kappa-statistic) in reporting according to Breast Imaging Reporting and Data System (BI-RADS((R))) breast density categories was tested in 12 dedicated breast radiologists reading a digitized set of 100 two-view mammograms. Average intraobserver agreement was substantial (kappa=0.71, range 0.32-0.88) on a four-grade scale (D1/D2/D3/D4) and almost perfect (kappa=0.81, range 0.62-1.00) on a two-grade scale (D1-2/D3-4). Average interobserver agreement was moderate (kappa=0.54, range 0.02-0.77) on a four-grade scale and substantial (kappa=0.71, range 0.31-0.88) on a two-grade scale. Major disagreement was found for intermediate categories (D2=0.25, D3=0.28). Categorization of breast density according to BI-RADS is feasible and consistency is good within readers and reasonable between readers. Interobserver inconsistency does occur, and checking the adoption of proper criteria through a proficiency test and appropriate training might be useful. As inconsistency is probably due to erroneous perception of classification criteria, standard sets of reference images should be made available for training.

Purpose: To evaluate the sensitivity of the mammographic screening programme and the causes of diagnostic fault in cases surfacing as interval cancers., Materials and Methods: Interval cancers (CI) were identified by linkage of the screening database for the years 2000-2002 to the database of hospital discharge records (HDR) for breast cancer during 2000-2002. Linkage between screening attenders during 2000-2001 and HDR (biennial follow-up for year 2000, one year follow-up for year 2001) was used to calculate the proportional rate of observed/expected IC. The observed/ expected rate was compared with international standards and literature data. Screening mammograms followed by IC, randomly admixtured with negative controls, underwent blind review by an independent radiologist, using the recommended classification criteria to evaluate causes of error (occult, minimal signs, screening error)., Results: The analysis of HDR during 2000-2002 allowed us to identify 31 out of 89 expected IC. Proportional observed/expected IC rate in the first or second year of screening interval was 26 or 67%, respectively. Screening mammograms for radiological review were available in 38 of 61 total IC: 20 cases (52.6%) were classified as occult, whereas minimal signs or screening errors were 2 (5.2%) or 16 (42.1%), respectively. Diagnostic suspicion had been reported at screening in 7 of 16 cases classified as screening error, but were not diagnosed at the subsequent diagnostic assessment., Conclusions: Proportional IC rate was higher than reported in the literature or currently recommended (<30% in the 1st, <50% in the 2nd year). The analysis of error causes shows an excess of screening errors with respect to current recommendations (<20% of IC should be classified as screening error at review), but also an excess of IC suspected at screening but misdiagnosed at assessment (7/38=18.4 %). Overall the analysis revealed a reduced sensitivity of the screening programme, as often observed in service screening as compared to excellence centres, and suggests proper action to improve diagnostic accuracy. Analysis and critical review of IC is an early indicator of screening efficacy which is not currently used in Italian screening programmes. Using HDR for this purpose may have limited drawbacks, but gives the advantage of earlier identification of IC as compared to cancer registries and is the most reliable source of information in areas lacking a cancer registry. The present study methodology might be currently applied in screening programmes.

Objective: To assess double reading effectiveness in mammography screening., Design: Retrospective study of 177,631 consecutive mammograms double read during 1998-2003., Setting: The Florence screening programme, involving 11 trained radiologists. Abnormalities reported by at least one reader prompted assessment., Results: The referral rate was 2.89% for the first reader, 3.15% for the second reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were suspected only by the second reader (6.4% relative, 0.024% increase in absolute detection rate) and had a lower stage compared to the first reader (pTis-pT1b = 65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in 20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman examined, or 11,168 per additional cancer detected (versus 11,585 at a single reading)., Discussion: Second reading is effective in detecting a limited number of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and review findings (high rate of "screening errors" and BI-RADS R4b-c categories) suggest that second reading detects small "difficult cases" as well as larger cancers missed due to fatigue or loss of attention. Second reading reduces screening specificity to a minor extent, and since cancer detection at second reading seems cost-effective the procedure is recommendable in routine practice.

Objective: To asses the effectiveness of arbitration of discordant double readings in mammography screening., Design: A retrospective study of 1217 consecutive arbitrations., Setting: A subset of discordant double readings from the Florence screening programme underwent arbitration by a third reader., Results: Positive arbitration of 1217 discordant double readings prompted assessment in 476 cases (39.2%), detecting 30 cancers (6.3%). Of 741 negative arbitrations (60.8%), 311 have been followed up thus far, and two cancers (0.64%) occurred in the site previously suspected at one of the two independent readings. Arbitration had a sensitivity of 86.3% and a negative predictive value of 99.3%. Arbitration reduced the overall referral rates from 3.82% to 2.59% (relative decrease 32.1%). Due to false-negative arbitration, cancers detected per 1000 women screened would decrease from 4.58 to 4.50 (relative decrease 1.7%). For every cancer missed due to false-negative arbitration, 151 unnecessary recalls and 21,248 euro would have been saved, whereas the saved cost per screened woman due to arbitration was 1.72 euro., Discussion: Arbitration of discordant double reading would substantially reduce referral rates with a limited reduction in cancer detection rate, and may be recommended as a routine procedure. Greater benefit from arbitration might be expected in the presence of high referral rates at independent double reading, a common scenario in a newly implemented service screening.

Purpose: To compare the diagnostic accuracy of two commercial CAD systems (CADx and R2) and their impact as an aid to conventional reading of screening mammograms., Materials and Methods: The image set considered consisted of 120 mammograms, 89 confirmed negative and 31 with subsequent interval cancers (11 classified as false negatives (FN), 20 as "minimal signs" (MS)). The set was digitised and processed with CAD, and printouts obtained of the mammograms with indications of the areas warranting review. Six expert radiologists read the mammograms three times, once using conventional reading and twice using CAD reading with CADx and R2, respectively. The two CAD systems were compared in terms of diagnostic accuracy of the marks and the impact of CAD reading compared to conventional reading and to the use of independent second reading simulated by combining pairs of single conventional readings., Results: R2 highlighted more calcifications (218 vs 132, +65%) and CADx highlighted more masses (208 vs 105, +98%). CADx and R2 marked 15 and 17 out of 31 cancers, respectively (sensitivity 48.3% vs 54.8%, chi squared=6.4, p=0.79), 10 and 6 out of 11 FN (90.9% vs 54.5%, chi squared=2.0, p=0.15), respectively, and 5 and 11 out of 20 MS (25.0% vs 55.0%, chi squared=2.6, p=0.10), respectively. As for specificity, the false positive markings for masses were on average (per case) 1.60 for CADx and 0.75 for R2, those for calcifications were 1.08 for CADx and 1.77 for R2 and the total false positive markings were 2.68 for CADx and 2.52 for R2. CADx and R2 marked 73 and 63 of 89 negative controls (specificity = 0.18 vs 0.29, chi squared=2.52, p=0.11), respectively. All the radiologists showed greater sensitivity with CAD reading compared to conventional reading. On average, sensitivity with conventional reading was 58.6% (109/186), as against 70.9% (132/186) for CADx or R2 (chi squared=5.71, p=0.016). Sensitivity for FN cases was 71.2% (47/66) with conventional reading, 84.8% (56/66) with CADx (chi squared=2.82, p=0.09) and 80.3% (53/66) for R2 (chi squared=1.03, p=0.30) (CADx vs R2, chi squared=0.21, p=0.64). Sensitivity for MS cases was 51.6% (62/120) for conventional reading, 63.3% (76/120) for CADx (chi squared=2.88, p=0.08) and 65.8% (79/120) for R2 (chi squared=4.40, p=0.03) (CADx vs R2, chi squared=0.07, p=0.78). The recall rates were 18.1% (97/534) for conventional reading, 29.7% (159/534) for CADx (chi squared=5.72, p=0.01) and 24.3% (130/534) for R2 (chi squared=10.11, p=10-5) (CADx vs R2, chi squared=3.71, p=0.05). Double reading was significantly more sensitive than conventional reading (chi squared=29.6, p=10-6), CADx (chi squared=5.33, p=0.02) and R2 (chi squared=5.33, p=0.02). The recall rate for double reading was significantly higher than for conventional reading (chi squared=21.5, p=10-6) whereas no significant difference was detected when compared to CADx (chi squared=0.16, p=0.68) or R2 (chi squared=3.4, p=0.06)., Conclusions: Despite using different algorithms, the two CAD systems exhibit comparable levels of diagnostic accuracy and a similar positive impact on sensitivity when used as an aid to conventional reading. Single reading with either CAD system is as specific but not as sensitive to double independent reading: its use as an alternative to double reading cannot be recommended and should be investigated further by means of controlled prospective studies.