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Neoadjuvant treatments (NAT) for breast cancer (BC) consist in the administration of chemotherapy-more rarely endocrine therapy-before surgery. Firstly, it was introduced 50 years ago to downsize locally advanced (inoperable) BCs. NAT are now widespread and so effective to be used also at the early stage of the disease. NAT are heterogeneous in terms of therapeutic patterns, class of used drugs, dosage, and duration. The poly-chemotherapy regimen and administration schedule are established by a multi-disciplinary team, according to the stage of disease, the tumor subtype and the age, the physical status, and the drug sensitivity of BC patients. Consequently, an accurate monitoring of treatment response can provide significant clinical advantages, such as the treatment de-escalation in case of early recognition of complete response or, on the contrary, the switch to an alternative treatment path in case of early detection of resistance to the ongoing therapy. Future is going toward increasingly personalized therapies and the prediction of individual response to treatment is the key to practice customized care pathways, preserving oncological safety and effectiveness. To gain such goal, the development of an accurate monitoring system, reproducible and reliable alone or as part of more complex diagnostic algorithms, will be promising., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

BACKGROUND. Contrast-enhanced mammography (CEM) is rapidly expanding as a credible alternative to MRI in various clinical settings. OBJECTIVE. The purpose of this study was to compare CEM and MRI for neoadjuvant therapy (NAT) response assessment in patients with breast cancer. METHODS. This prospective study included 51 patients (mean age, 46 ± 11 [SD] years) with biopsy-proven breast cancer who were candidates for NAT from May 2015 to April 2018. Patients underwent both CEM and MRI before, during, and after NAT (pre-NAT, mid-NAT, and post-NAT, respectively). Post-NAT CEM included a 6-minute delayed acquisition. One breast radiologist with experience in CEM reviewed CEM examinations; one breast radiologist with experience in MRI reviewed MRI examinations. The radiologists assessed for the presence of an enhancing lesion; if an enhancing lesion was detected, its size was measured. RECIST version 1.1 response assessment categories were derived. Pathologic complete response (pCR) was defined as absence of both invasive cancer and ductal carcinoma in situ (DCIS). RESULTS. Of 51 patients, 16 achieved pCR. CEM yielded systematically lower size measurements compared with MRI (mean difference, -0.2 mm for pre-NAT, -0.7 mm for mid-NAT, and -0.3 mm for post-NAT). All post-NAT imaging tests yielded systematically larger size measurements compared with pathology (mean difference, 0.8 mm for CEM, 1.2 mm for MRI, and 1.9 mm for delayed CEM). Of 12 patients with residual DCIS, an enhancing lesion was detected in seven on post-NAT CEM, eight on post-NAT MRI, and nine on post-NAT delayed CEM. Agreement of RECIST response categories between CEM and MRI, expressed as kappa coefficient, was 0.791 at mid-NAT and 0.871 at post-NAT. For detecting pCR by post-NAT imaging, sensitivity and specificity were 81% and 83% for CEM, 100% and 86% for MRI, and 81% and 89% for delayed CEM. Sensitivity was significantly higher for MRI than CEM ( p = .001) and delayed CEM ( p = .002); remaining comparisons were not significant ( p > .05). CONCLUSION. After NAT for breast cancer, CEM and MRI yielded comparable assessments of lesion size (both slightly overestimated vs pathology) and RECIST categories and showed no significant difference in specificity for pCR. MRI had higher sensitivity for pCR. Delayed CEM acquisition may help detect residual DCIS. CLINICAL IMPACT. Although MRI remains the preferred test for NAT response monitoring, the findings support CEM as a useful alternative when MRI is contraindicated or not tolerated.

Italy was the first western country to be hit by the initial wave of severe adult respiratory syndrome coronavirus 2 pandemic, which has been more widespread in the country's northern regions. Early reports showing that cancer patients are more susceptible to the infection posed a particular challenge that has guided our Breast Unit at Hub Hospital in Trento to making a number of stepwise operational changes. New internal guidelines and treatment selection criteria were drawn up by a virtual multidisciplinary tumour board that took into account the risks and benefits of treatment, and distinguished the patients requiring immediate treatment from those whose treatment could be delayed. A second wave of the pandemic is expected in the autumn as gatherings in closed places increase. We will take advantage of the gained experience and organisational changes implemented during the first wave in order to improve further, and continue to offer breast cancer management and treatment to our vulnerable patient population., (© 2021 John Wiley & Sons Ltd.)

Competing Interests: Dr Ferro has received speaker honoraria from Eli Lilly, Novartis and Pfizer. Orazio Caffo has served as advisor or speaker for Astellas, Astra Zeneca, Janssen, Sanofi and Pfizer. All other authors have no conflicts of interest to declare.

Background/aim: The Trento screening program transitioned to digital breast tomosynthesis (DBT) screening based on evidence that DBT improves breast cancer (BC) detection compared to mammography; an evaluation of the transition to DBT is reported in this pilot study., Methods: Prospective implementation of DBT screening included women aged ≥50 years who attended the Trento program for biennial screening. DBT screening included DBT acquisitions with synthesized 2D-images. A historical cohort of women who attended the program (January 2013-October 2014) and received digital mammography (DM) provided a comparison group. Independent double-reading (with a third arbitrating read for discordance) was used for DBT and DM screening. Screening outcomes included cancer detection rate (CDR/1000 screens), percentage of screens recalled to assessment (recall%), interval cancer rate (ICR/1000 screens) at 2-year follow-up, and screening sensitivity. Rate ratios (RR) and 95% confidence interval (95%CI) examined outcomes for DBT versus DM screening., Results: From women aged 50-69 years who accepted an invitation to screening (October 2014-October 2016) 46,343 comprised the DBT-screened group: amongst these 402 BCs (includes 50 ductal carcinoma in-situ (DCIS)) were detected (CDR 8.67/1000), whereas 205 BCs (includes 33 DCIS) were detected amongst 37,436 DM screens (CDR 5.48/1000) [RR for CDR:1.58 (1.34-1.87)]. Recall% was lower for DBT (2.55%) than DM (3.21%) [RR:0.79 (0.73-0.86)]. Compared to DM, DBT screening increased CDR for stage I-II BC, for all tumour size and grade categories, and for node-negative BC, but did not increase CDR for DCIS. Estimated ICR for DBT was 1.1/1000 whereas ICR for DM was 1.36/1000 [RR:0.81 (0.55-1.19)]. Screening sensitivity was 88.74% for DBT versus 80.08% for DM [RR:1.11 (0.94-1.31)]., Conclusion: DBT significantly improved early-detection measures but did not significantly reduce ICR (relative to DM screening), suggesting that it could add benefit as well as adding over-detection in population BC screening., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We previously reported the Screening with tomosynthesis or standard mammography-2 (STORM-2) trial, showing that tomosynthesis (3D-mammography) screening detected more cancers than 2D-mammography in double-reading practice. In this study, we report reader-specific detection measures for radiologists who performed the screen-reading in this trial., Methods: This is a sub-study of the STORM-2 trial which prospectively integrated 3D-mammography with acquired or synthetized 2D-mammograms in parallel double-reading arms. Asymptomatic women ≥49 years who attended population-based screening (Trento, 2013-2015) were recruited. Screening participants were recalled at any positive sequential screen-read in either reading arm of the trial. Radiologist-specific detection measures were calculated for each of seven radiologists who performed screen-reads: number of detected cancers, proportion of true-positive (TP) detection, and number and rate of false-positive (FP) recalls (FPR). We estimated incremental cancer detection rate (CDR) from integrating 3D-mammography in screen-reading., Results: Across all radiologists, TP detection (relative sensitivity) ranged between: 46% and 100% (median 59.5%) for 2D-mammography; 75% and 100% (median 76%) for integrated 2D/3D-mammography screening; 56% and 76% (median 64%) for 2Dsynthetic; 67% and 88% (median 78%) for 2Dsynthetic/3D-mammography. Integrating 3D-mammography led to incremental CDRs between 0/1000 and 3.5/1000 screens. FPR ranged between: 1.2% and 2.7% (median 2.25%) for 2D-mammography; 1.5% and 3.4% (median 2.75%) for 2D/3D-mammography; 1.6% and 4.6% (median 2.4%) for 2Dsynthetic; and 1.8% and 6.7% (median 3.0%) for 2Dsynthetic/3D-mammography., Conclusions: There was variability in the magnitude of effect from integrating 3D-mammography (relative to screen-reading with acquired or synthesised 2D-mammography alone) on individual radiologist's TP and FP detection, although there was an overall pattern of increasing cancer detection and also increasing FP recall for most readers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background & Methods: The prospective 'screening with tomosynthesis or standard 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 tomosynthesis (integrated 2D/3D-mammography). The STORM trial showed that tomosynthesis 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 tomosynthesis screening versus digital mammography screening., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Most population breast cancer (BC) screening programs use double-reading of 2D-mammography. We recently reported the screening with tomosynthesis or standard mammography-2 (STORM-2) trial, showing that double-read tomosynthesis (pseudo-3D-mammography) detected more BC than double-read 2D-mammography. In this study, we compare screen-detection measures for single-reading of 3D-mammography with those for double-reading of 2D-mammography, to inform screening practice., Methods: This is a secondary analysis based on STORM-2 which prospectively compared 3D-mammography and 2D-mammography in sequential screen-readings. Asymptomatic women ≥49 years who attended population-based screening (Trento, 2013-2015) were recruited. Participants recalled at any screen-read from parallel double-reading arms underwent further testing and/or biopsy. Single-reading of 3D-mammography, integrated with acquired or synthetized 2D-mammograms, was compared to double-reading of 2D-mammograhy alone for screen-detection measures: number of detected BCs, cancer detection rate (CDR), number and percentage of false-positive recall (FPR). Paired binary data were compared using McNemar's test., Results: Screening detected 90, including 74 invasive, BCs in 85 of 9672 participants. CDRs for single-reading using integrated 2D/3D-mammography (8.2 per 1000 screens; 95% CI 6.5-10.2) or 2D synthetic/3D-mammography (8.4 per 1000 screens; 95% CI: 6.7-10.4) were significantly higher than CDR for double-reading of 2D-mammography (6.3 per 1000 screens; 95% CI: 4.8-8.1), P<0.001 both comparisons. FPR% for single-read 2D/3D-mammography (2.60%; 95% CI: 2.29-2.94), or single-read 2D synthetic/3D-mammography (2.76%; 95% CI: 2.45-3.11), were significantly lower than FPR% for double-read 2D-mammography (3.42%; 95% CI: 3.07-3.80), P<0.001 and P=0.002 respectively., Conclusions: Single-reading of 3D-mammography (integrated 2D/3D or 2Dsynthetic/3D) detected more BC, and had lower FPR, compared to current practice of double-reading 2D-mammography alone - these findings have implications for population BC screening programs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Breast tomosynthesis (pseudo-3D mammography) improves breast cancer detection when added to 2D mammography. In this study, we examined whether integrating 3D mammography with either standard 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 Tomosynthesis Or standard Mammography-2 (STORM-2) study was a prospective 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., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objectives: To compare breast density (BD) assessment provided by an automated BD evaluator (ABDE) with that provided by a panel of experienced breast radiologists, on a multivendor dataset., Methods: Twenty-one radiologists assessed 613 screening/diagnostic digital mammograms from nine centers and six different vendors, using the BI-RADS a, b, c, and d density classification. The same mammograms were also evaluated by an ABDE providing the ratio between fibroglandular and total breast area on a continuous scale and, automatically, the BI-RADS score. A panel majority report (PMR) was used as reference standard. Agreement (κ) and accuracy (proportion of cases correctly classified) were calculated for binary (BI-RADS a-b versus c-d) and 4-class classification., Results: While the agreement of individual radiologists with the PMR ranged from κ = 0.483 to κ = 0.885, the ABDE correctly classified 563/613 mammograms (92 %). A substantial agreement for binary classification was found for individual reader pairs (κ = 0.620, standard deviation [SD] = 0.140), individual versus PMR (κ = 0.736, SD = 0.117), and individual versus ABDE (κ = 0.674, SD = 0.095). Agreement between ABDE and PMR was almost perfect (κ = 0.831)., Conclusions: The ABDE showed an almost perfect agreement with a 21-radiologist panel in binary BD classification on a multivendor dataset, earning a chance as a reproducible alternative to visual evaluation., Key Points: Individual BD assessment differs from PMR with κ as low as 0.483. An ABDE correctly classified 92 % of mammograms with almost perfect agreement (κ = 0.831). An ABDE can be a valid alternative to subjective BD assessment.

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.)

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.)