Mammographic features and risk of breast cancer death among women with invasive screen-detected cancer in BreastScreen Norway 1996-2020.

OBJECTIVES: We explored associations between mammographic features and risk of breast cancer death among women with small (<15 mm) and large (≥15 mm) invasive screen-detected breast cancer. METHODS: We included data from 17,614 women diagnosed with invasive breast cancer as a result of participation in BreastScreen Norway, 1996-2020. Data on mammographic features (mass, spiculated mass, architectural distortion, asymmetric density, density with calcification and calcification alone), tumour diameter and cause of death was obtained from the Cancer Registry of Norway. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (CI) for breast cancer death by mammographic features using spiculated mass as reference, adjusting for age, tumour diameter and lymph node status. All analyses were dichotomised by tumour diameter (small versus large). RESULTS: Mean age at diagnosis was 60.8 (standard deviation, SD=5.8) for 10,160 women with small tumours and 60.0 (SD=5.8) years for 7454 women with large tumours. The number of breast cancer deaths was 299 and 634, respectively. Mean time from diagnosis to death was 8.7 (SD=5.0) years for women with small tumours and 7.2 (4.6) years for women with large tumours. Using spiculated mass as reference, adjusted HR for breast cancer death among women with small tumours was 2.48 (95% CI 1.67-3.68) for calcification alone, while HR for women with large tumours was 1.30 (95% CI 1.02-1.66) for density with calcification. CONCLUSIONS: Small screen-detected invasive cancers presenting as calcification and large screen-detected cancers presenting as density with calcification were associated with the highest risk of breast cancer death. CLINICAL RELEVANCE STATEMENT: Small tumours (<15 mm) presented as calcification alone and large tumours (≥ 15 mm) presented as density with calcification were associated with the highest risk of breast cancer death among women with screen-detected invasive breast cancer diagnosed 1996-2020. KEY POINTS: • Women diagnosed with invasive screen-detected breast cancer 1996-2020 were analysed. • Small screen-detected cancers presenting as calcification alone resulted in the highest risk of breast cancer death. • Large screen-detected cancers presenting as density with calcification resulted in the highest risk of breast cancer death.

Discordant and false-negative interpretations at digital breast tomosynthesis in the prospective Oslo Tomosynthesis Screening Trial (OTST) using independent double reading.

OBJECTIVES: To analyze discordant and false-negatives of double reading digital breast tomosynthesis (DBT) versus digital mammography (DM) including reading times in the Oslo Tomosynthesis Screening Trial (OTST), and reclassify these in a retrospective reader study as missed, minimal sign, or true-negatives. METHODS: The prospective OTST comparing double reading DBT vs. DM had paired design with four parallel arms: DM, DM + computer aided detection, DBT + DM, and DBT + synthetic mammography. Eight radiologists interpreted images in batches using a 5-point scale. Reading time was automatically recorded. A retrospective reader study including four radiologists classified screen-detected cancers with at least one false-negative score and screening examinations of interval cancers as negative, non-specific minimal sign, significant minimal sign, and missed; the two latter groups are defined "actionable." Statistics included chi-square, Fisher's exact, McNemar's, and Mann-Whitney U tests. RESULTS: Discordant rate (cancer missed by one reader) for screen-detected cancers was overall comparable (DBT (31% [71/227]) and DM (30% [52/175]), p = .81), significantly lower at DBT for spiculated cancers (DBT, 19% [20/106] vs. DM, 36% [38/106], p = .003), but high (28/49 = 57%, p = 0.001) for DBT-only detected spiculated cancers. Reading time and sensitivity varied among readers. False-negative DBT-only detected spiculated cancers had shorter reading time than true-negatives in 46% (13/28). Retrospective evaluation classified the following DBT exams "actionable": three missed by both readers, 95% (39/41) of discordant cancers detected by both modes, all 30 discordant DBT-only cancers, 25% (13/51) of interval cancers. CONCLUSIONS: Discordant rate was overall comparable for DBT and DM, significantly lower at DBT for spiculated cancers, but high for DBT-only detected spiculated lesions. Most false-negative screen-detected DBT were classified as "actionable." CLINICAL RELEVANCE STATEMENT: Retrospective evaluation of false-negative interpretations from the Oslo Tomosynthesis Screening Trial shows that most discordant and several interval cancers could have been detected at screening. This underlines the potential for modern AI-based reading aids and triage, as high-volume screening is a demanding task. KEY POINTS: • Digital breast tomosynthesis (DBT) screening is more sensitive and has higher specificity compared to digital mammography screening, but high-volume DBT screening is a demanding task which can result in high discordance rate among readers. • Independent double reading DBT screening had overall comparable discordance rate as digital mammography, lower for spiculated masses seen on both modalities, and higher for small spiculated cancer seen only on DBT. • Almost all discordant digital breast tomosynthesis-detected cancers (72 of 74) and 25% (13 of 51) of the interval cancers in the Oslo Tomosynthesis Screening Trial were retrospectively classified as actionable and could have been detected by the readers.

Interval and Consecutive Round Breast Cancer after Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Standard 2D Digital Mammography in BreastScreen Norway.

Background Screening that includes digital breast tomosynthesis (DBT) with two-dimensional (2D) synthetic mammography (SM) or standard 2D digital mammography (DM) results in detection of more breast cancers than does screening with DM alone. A decrease in interval breast cancer rates is anticipated but is not reported. Purpose To compare rates and characteristics of (a) interval breast cancer in women screened with DBT and SM versus those screened with DM alone and (b) screen-detected breast cancer at consecutive screenings with DM. Materials and Methods This prospective cohort study from BreastScreen Norway included women screened with DBT and SM (study group) or DM alone (control group) between February 2014 and December 2015 (baseline). All women, except nonattendees, women with breast cancer, and those who exceeded the upper age limit, were consecutively screened with DM after 2 years. Interval breast cancer, sensitivity, and specificity were estimated for women screened at baseline. Recall, screen-detected breast cancer, and positive predictive value were analyzed for consecutively screened women. A χ2 test, t test (P < .001 after Bonferroni correction indicated a significant difference), and binomial regression model were used to analyze differences across groups. Results A total of 92 404 women who underwent baseline screening (mean age, 59 years ± 6 [standard deviation]) were evaluated; 34 641 women in the study group (mean age, 59 years ± 6) were screened with DBT and SM and 57 763 women in the control group (mean age, 59 years ± 6) were screened with DM. A total of 26 474 women in the study group (mean age, 60 years ± 5) and 45 543 women in the control group (mean age, 60 years ± 5) were consecutively screened with DM. Rates of interval breast cancer were 2.0 per 1000 screened women in the study group and 1.5 per 1000 screened women in the control group (P = .12). No differences in histopathologic characteristics of interval breast cancer were observed. In the consecutive screening round, rates of screen-detected breast cancer were 3.9 per 1000 screened women (study group) and 5.6 per 1000 screened women (control group) (P = .001). Rates of histologic grade 1 invasive cancer were 0.5 per 1000 screened women (study group) and 1.3 per 1000 screened women (control group) (P = .001). Conclusion No differences in interval breast cancer rates or tumor characteristics were observed in women screened with DBT and SM compared with women screened with DM. Higher rates of low-grade screen-detected tumors were observed in the control group at consecutive screening. © RSNA, 2019 Online supplemental material is available for this article.

Digital Mammography versus Breast Tomosynthesis: Impact of Breast Density on Diagnostic Performance in Population-based Screening.

BackgroundPrevious studies comparing digital breast tomosynthesis (DBT) to digital mammography (DM) have shown conflicting results regarding breast density and diagnostic performance.PurposeTo compare true-positive and false-positive interpretations in DM versus DBT according to volumetric density, age, and mammographic findings.Materials and MethodsFrom November 2010 to December 2012, 24 301 women aged 50-69 years (mean age, 59.1 years ± 5.7) were prospectively included in the Oslo Tomosynthesis Screening Trial. Participants received same-compression DM and DBT with independent double reading for both DM and DM plus DBT reading modes. Eight experienced radiologists rated the images by using a five-point scale for probability of malignancy. Participants were followed up for 2 years to assess for interval cancers. Breast density was assessed by using automatic volumetric software (scale, 1-4). Differences in true-positive rates, false-positive rates, and mammographic findings were assessed by using confidence intervals (Newcombe paired method) and P values (McNemar and χ2 tests).ResultsThe true-positive rate of DBT was higher than that of DM for density groups (range, 12%-24%; P < .001 for density scores of 2 and 3, and P > .05 for density scores of 1 and 4) and age groups (range, 15%-35%; P < .05 for all age groups), mainly due to the higher number of spiculated masses and architectural distortions found at DBT (P < .001 for density scores of 2 and 3; P < .05 for women aged 55-69 years). The false-positive rate was lower for DBT than for DM in all age groups (range, -0.6% to -1.2%; P < .01) and density groups (range, -0.7 to -1.0%; P < .005) owing to fewer asymmetric densities (P ≤ .001), except for extremely dense breasts (0.1%, P = .82).ConclusionDigital breast tomosynthesis enabled the detection of more cancers in all density and age groups compared with digital mammography, especially cancers classified as spiculated masses and architectural distortions. The improvement in cancer detection rate showed a positive correlation with age. With use of digital breast tomosynthesis, false-positive findings were lower due to fewer asymmetric densities, except in extremely dense breasts.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Fuchsjäger and Adelsmayr in this issue.

Digital Mammography versus Digital Mammography Plus Tomosynthesis in Breast Cancer Screening: The Oslo Tomosynthesis Screening Trial.

Background Digital breast tomosynthesis (DBT) is replacing digital mammography (DM) in the clinical workflow. Currently, there are limited prospective studies comparing the diagnostic accuracy of both examinations and the role of synthetic mammography (SM) and computer-aided detection (CAD). Purpose To compare the accuracy of DM versus DM + DBT in population-based breast cancer screening. Materials and Methods This prospective study, performed from November 2010 to December 2012, included 24 301 women (mean age, 59.1 years ± 5.7 [standard deviation]) with 281 cancers, of which 51 were interval cancers. Each examination was independently interpreted with four reading modes: DM, DM + CAD, DM + DBT, and SM + DBT. Sensitivity and specificity were compared for DM versus DM + DBT, DM versus DM + CAD, DM + DBT versus SM + DBT, and DM versus DM + DBT at double reading. Reader-adjusted performance characteristics of reading modes were evaluated on the basis of pre-arbitration (initial interpretation) scores. Statistical analysis was based on cluster bootstrap analysis using 10 000 random resamples. Results Sensitivity was 54.1% (152 of 281) for DM and 70.5% (198 of 281) for DM + DBT. Reader-adjusted difference was 12.6% (95% confidence interval [CI]: 5.2%, 19.7%; P = .001). Specificity was 94.2% (false-positive fraction [FPF], 5.8%; 1388 of 24 020) for DM and 95.0% (FPF, 5.0%; 1209/24 020) for DM + DBT, with a reader-adjusted difference in FPF of -1.2% (95% CI: -1.7%, -0.7%; P < .001). Sensitivity was 69.0% (194 of 281) for SM + DBT and 70.5% (198 of 281) for DM + DBT, with a reader-adjusted difference of 1.0% (95% CI: -6.2%, 8.5%; P = .77). Specificity was 95.4% (FPF, 4.6%; 1111 of 24 020) for SM + DBT and 95.0% (FPF, 5.0%;1209 of 24 020) for DM + DBT, with reader-adjusted 95% CIs for FPF of 4.7%, 5.4% and 5.0%, 5.7%, respectively, and a difference of -0.3% (95% CI: -0.8%, 0.2%; P = .23). Differences in sensitivity and specificity with the addition of CAD were small and not significant (P > .2). Conclusion Addition of digital breast tomosynthesis to digital mammography resulted in significant gains in sensitivity and specificity. Synthetic mammography in combination with digital breast tomosynthesis had similar sensitivity and specificity to digital mammography in combination with digital breast tomosynthesis. © RSNA, 2019 See also the editorial by Lång in this issue.

Screening outcome for consecutive examinations with digital breast tomosynthesis versus standard digital mammography in a population-based screening program.

OBJECTIVES: To retrospectively investigate early performance measures of digital breast tomosynthesis (DBT) versus standard digital mammography (DM) for consecutive screening rounds. METHODS: We included information about 35,736 women screened in BreastScreen Norway, 2008-2016, with at least two consecutive screening examinations. The pair of two consecutive screening examinations was the unit of analysis, and results from the subsequent examination were the measure of interest. Screening technique changed during the study period, resulting in four study groups: DM after DM, DBT after DM, DM after DBT, and DBT after DBT. We compared selected early performance measures between the study groups. RESULTS: Recall for DM after DM was 3.6% and lower for all other study groups (p < 0.001). The rate of screen-detected breast cancer was 4.6/1000 for DM after DM; for DBT after DM and DBT after DBT, it was 9.9/1000 and 8.3/1000, respectively (p < 0.001 relative to DM after DM), and for DM after DBT 4.3/1000. The rate of tubular carcinoma was higher for DBT after DBT or after DM compared with DM after DM (p < 0.01). The rate of histologic grade 1 tumors was higher for DBT after DM compared with DM after DM (p < 0.001). We did not observe any statistical difference in the interval cancer rates. CONCLUSIONS: Lower recall and higher cancer detection rates for screening with DBT were sustainable over two consecutive screening rounds. Positive predictive values were higher for DBT than DM. There were no differences in the interval cancer rates between the study groups. KEY POINTS: • There is limited knowledge about early performance measures for screening with digital breast tomosynthesis beyond one screening round. • A decline in recall rate and an incline in the rate of screen-detected breast cancer were observed for women screened with DBT compared with DM, irrespective of prior screening technique. The interval breast cancer rate did not differ statistically for women screened with DBT versus DM. • Tumor characteristics tended to be prognostic favorable for DBT compared with DM with no differences in rates of more advanced cancers. The clinical significance of increased cancer detection and the potential for future mortality reduction remain unknown.

Performance of breast cancer screening using digital breast tomosynthesis: results from the prospective population-based Oslo Tomosynthesis Screening Trial.

PURPOSE: Digital breast tomosynthesis (DBT) has the potential to overcome limitations of conventional mammography. This study investigated the effects of addition of DBT on interval and detected cancers in population-based screening. METHODS: Oslo Tomosynthesis Screening Trial (OTST) was a prospective, independent double-reading trial inviting women 50-69 years biennially, comparing full-field digital mammography (FFDM) plus DBT with FFDM alone. Performance indicators and characteristics of screen-detected and interval cancers were compared with two previous FFDM rounds. RESULTS: 24,301 consenting women underwent FFDM + DBT screening over a 2-year period. Results were compared with 59,877 FFDM examinations during prior rounds. Addition of DBT resulted in a non-significant increase in sensitivity (76.2%, 378/496, vs. 80.8%, 227/281, p = 0.151) and a significant increase in specificity (96.4%, 57229/59381 vs. 97.5%, 23427/24020, p < .001). Number of recalls per screen-detected cancer decreased from 6.7 (2530/378) to 3.6 (820/227) with DBT (p < .001). Cancer detection per 1000 women screened increased (6.3, 378/59877, vs. 9.3, 227/24301, p < .001). Interval cancer rate per 1000 screens for FFDM + DBT remained similar to previous FFDM rounds (2.1, 51/24301 vs. 2.0, 118/59877, p = 0.734). Interval cancers post-DBT were comparable to prior rounds but significantly different in size, grade, and node status from cancers detected only using DBT. 39.6% (19/48) of interval cancers had positive nodes compared with only 3.9% (2/51) of additional DBT-only-detected cancers. CONCLUSIONS: DBT-supplemented screening resulted in significant increases in screen-detected cancers and specificity. However, no significant change was observed in the rate, size, node status, or grade of interval cancers. ClinicalTrials.gov: NCT01248546.

Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Digital Mammography: Evaluation in a Population-based Screening Program.

Purpose To compare the performance of digital breast tomosynthesis (DBT) and two-dimensional synthetic mammography (SM) with that of digital mammography (DM) in a population-based mammographic screening program. Materials and Methods In this prospective cohort study, data from 37 185 women screened with DBT and SM and from 61 742 women screened with DM as part of a population-based screening program in 2014 and 2015 were included. Early performance measures, including recall rate due to abnormal mammographic findings, rate of screen-detected breast cancer, positive predictive value of recall, positive predictive value of needle biopsy, histopathologic type, tumor size, tumor grade, lymph node involvement, hormonal status, Ki-67 level, and human epidermal growth factor receptor 2 status were compared in women who underwent DBT and SM screening and in those who underwent DM screening by using χ2 tests, two-sample unpaired t tests, and tests of proportions. Results Recall rates were 3.4% for DBT and SM screening and 3.3% for DM screening (P = .563). DBT and SM screening showed a significantly higher rate of screen-detected cancer compared with DM screening (9.4 vs 6.1 cancers per 1000 patients screened, respectively; P < .001). The rate of detection of tumors 10 mm or smaller was 3.2 per 1000 patients screened with DBT and SM and 1.8 per 1000 patients screened with DM (P < .001), and the rate of grade 1 tumors was 3.3 per 1000 patients screened with DBT and SM versus 1.4 per 1000 patients screened with DM (P < .001). On the basis of immunohistochemical analyses, rates of lymph node involvement and tumor subtypes did not differ between women who underwent DBT and SM screening and those who underwent DM screening. Conclusion DBT and SM screening increased the detection rate of histologically favorable tumors compared with that attained with DM screening. © RSNA, 2018 Online supplemental material is available for this article.

Classification of fatty and dense breast parenchyma: comparison of automatic volumetric density measurement and radiologists' classification and their inter-observer variation.

BACKGROUND: Automatically calculated breast density is a promising alternative to subjective BI-RADS density assessment. However, such software needs a cutoff value for density classification. PURPOSE: To determine the volumetric density threshold which classifies fatty and dense breasts with highest accuracy compared to average BI-RADS density assessment, and to analyze radiologists' inter-observer variation. MATERIAL AND METHODS: A total of 537 full field digital mammography examinations were randomly selected from a population based screening program. Five radiologists assessed density using the BI-RADS density scale, where BI-RADS I-II were classified as fatty and III-IV as dense. A commercially available software (Quantra) calculated volumetric breast density. We calculated the cutoff (threshold) values in volumetric density that yielded highest accuracy compared to median and individual radiologists' classification. Inter-observer variation was analyzed using the kappa statistic. RESULTS: The threshold that best matched the median radiologists' classification was 10%, which resulted in 87% accuracy. Thresholds that best matched individual radiologist's classification had a range of 8-15%. A total of 191 (35.6 %) cases were scored both dense and fatty by at least one radiologist. Fourteen (2.6 %) cases were unanimously scored by the radiologists, yet differently using automatic assessment. The agreement (kappa) between reader's median classification and individual radiologists was 0.624 to 0.902, and agreement between median classification and Quantra was 0.731. CONCLUSION: The optimal volumetric threshold of 10% using automatic assessment would classify breast parenchyma as fatty or dense with substantial accuracy and consistency compared to radiologists' BI-RADS categorization, which suffers from high inter-observer variation.

Breast MRI: EUSOBI recommendations for women's information.

UNLABELLED: This paper summarizes information about breast MRI to be provided to women and referring physicians. After listing contraindications, procedure details are described, stressing the need for correct scheduling and not moving during the examination. The structured report including BI-RADS® categories and further actions after a breast MRI examination are discussed. Breast MRI is a very sensitive modality, significantly improving screening in high-risk women. It also has a role in clinical diagnosis, problem solving, and staging, impacting on patient management. However, it is not a perfect test, and occasionally breast cancers can be missed. Therefore, clinical and other imaging findings (from mammography/ultrasound) should also be considered. Conversely, MRI may detect lesions not visible on other imaging modalities turning out to be benign (false positives). These risks should be discussed with women before a breast MRI is requested/performed. Because breast MRI drawbacks depend upon the indication for the examination, basic information for the most important breast MRI indications is presented. Seventeen notes and five frequently asked questions formulated for use as direct communication to women are provided. The text was reviewed by Europa Donna-The European Breast Cancer Coalition to ensure that it can be easily understood by women undergoing MRI. KEY POINTS: • Information on breast MRI concerns advantages/disadvantages and preparation to the examination • Claustrophobia, implantable devices, allergic predisposition, and renal function should be checked • Before menopause, scheduling on day 7-14 of the cycle is preferred • During the examination, it is highly important that the patient keeps still • Availability of prior examinations improves accuracy of breast MRI interpretation.

Interpretation of automated breast ultrasound (ABUS) with and without knowledge of mammography: a reader performance study.

BACKGROUND: Automated breast ultrasonography (ABUS) has the potential to be an important adjunct to mammography in women with dense breasts. PURPOSE: To compare reader performance and inter-observer variation of ABUS alone and in combination with mammography. MATERIAL AND METHODS: This retrospective study had ethical committee approval. All women gave written informed consent. One hundred and fourteen breasts in 90 women examined by digital mammography and ABUS were interpreted by five radiologists using BI-RADS categories. The 114 breasts included 38 cancers and 76 normal or benign findings. In the first reading session ABUS only was interpreted, and in the second ABUS plus digital mammography. Image interpretations were done without knowledge of clinical or imaging results. A consensus panel analyzed false negative and false positive interpretations. Reading time was recorded for one radiologist. AUC was used for performance measurement, and kappa statistic for inter-observer variability. RESULTS: Mean size for cancers was 16.2 mm; area under the curve (AUC) values for ABUS alone and for combined reading were, respectively: reader A, 0.592-0.744; reader B, 0.740-0.947; reader, C 0.759-0.823; reader D, 0.670-0.688; reader E, 0.904-0.923; and all readers combined 0.730-0.823. The higher AUC for combined reading was statistically significant (P < 0.05) for reader B and for all readers. There was a considerable inter-observer variability. Observer agreement revealed following kappa values for ABUS alone and combined reading, respectively: reader A, 0.22-0.30; reader B, 0.33-0.44; reader C, 0.32-0.39; reader D, 0.07-0.14; and reader E, 0.34-0.43. Shadowing from dense parenchyma was the most common cause of false positive ABUS interpretations. Mean interpretation time for a bilateral normal ABUS examination was 9 min. CONCLUSION: Observer agreement was higher and all radiologists improved diagnostic performance using combined ABUS and mammography interpretation. Combined reading should be standard if ABUS is implemented in screening of women with dense breasts.

Mammographic performance in a population-based screening program: before, during, and after the transition from screen-film to full-field digital mammography.

PURPOSE: To compare performance measures before, during, and after the transition from screen-film mammography (SFM) to full-field digital mammography (FFDM) in a population-based screening program. MATERIALS AND METHODS: No institutional review board approval was required for this analysis involving anonymized data for women aged 50-69 years enrolled in the Norwegian Breast Cancer Screening Program during 1996-2010. The χ(2) test was used to examine the equality of proportions of recall rates, positive predictive value of recall examinations and of invasive procedures, in addition to rates of screening-detected and interval cancers in women initially screened with SFM and FFDM and for women subsequently screened with SFM after SFM, FFDM after SFM, and FFDM after FFDM. RESULTS: The recall rate was 3.4% (47 091 of 1 391 188) for SFM and 2.9% (13 130 of 446 172) for FFDM (P < .001). The biopsy rate was 1.4% (19 776 of 1 391 188) for SFM and 1.1% (5108 of 446 172) for FFDM (P < .001). The rate of screening-detected ductal carcinoma in situ was higher (P = .019) while the rate of invasive breast cancer was lower (P < .001) for FFDM compared with those for SFM. The rate of both invasive screening-detected and interval breast cancer remained stable during the transition from SFM to FFDM (when the previous examination was SFM) and after FFDM was firmly established (when the previous examination was FFDM, >25 months after FFDM adoption) (P < .05). The positive predictive value of recall examinations and of invasive procedures increased from 19.3% (4559 of 23 598) and 48.3% (4651 of 9623) to 22.7% (681 of 2995) and 57.5% (689 of 1198), respectively, after adoption of FFDM (P < .001). CONCLUSION: After the initial transitional phase from SFM to FFDM, population-based screening with FFDM is associated with less harm because of lower recall and biopsy rates and higher positive predictive values after biopsy than screening with SFM.

Two-view digital breast tomosynthesis screening with synthetically reconstructed projection images: comparison with digital breast tomosynthesis with full-field digital mammographic images.

PURPOSE: To compare the performance of two versions of reconstructed two-dimensional (2D) images in combination with digital breast tomosynthesis (DBT) versus the performance of standard full-field digital mammography (FFDM) plus DBT. MATERIALS AND METHODS: This trial had ethical committee approval, and all participants gave written informed consent. Examinations (n = 24 901) in women between the ages of 50 and 69 years (mean age, 59.2 years) were interpreted prospectively as part of a screening trial that included independent interpretations of FFDM plus DBT and reconstructed 2D images plus DBT. Reconstructed 2D images do not require radiation exposure. Using analyses for binary data that accounted for correlated interpretations and were adjusted for reader-specific volume, two versions (initial and current) of reconstructed 2D images used during trial periods 1 (from November 22, 2010, to December 21, 2011; 12 631 women) and 2 (from January 20, 2012, to December 19, 2012; 12 270 women) were compared in terms of cancer detection and false-positive rates with the corresponding FFDM plus DBT interpretations. RESULTS: Cancer detection rates were 8.0, 7.4, 7.8, and 7.7 per 1000 screening examinations for FFDM plus DBT in period 1, initial reconstructed 2D images plus DBT in period 1, FFDM plus DBT in period 2, and current reconstructed 2D images plus DBT in period 2, respectively. False-positive scores were 5.3%, 4.6%, 4.6%, and 4.5%, respectively. Corresponding reader-adjusted paired comparisons of false-positive scores revealed significant differences for period 1 (P = .012) but not for period 2 (ratio = 0.99; 95% confidence interval: 0.88, 1.11; P = .85). CONCLUSION: The combination of current reconstructed 2D images and DBT performed comparably to FFDM plus DBT and is adequate for routine clinical use when interpreting screening mammograms.

Digital breast tomosynthesis in mammographic screening: false negative cancer cases in the To-Be 1 trial.

OBJECTIVES: The randomized controlled trial comparing digital breast tomosynthesis and synthetic 2D mammograms (DBT + SM) versus digital mammography (DM) (the To-Be 1 trial), 2016-2017, did not result in higher cancer detection for DBT + SM. We aimed to determine if negative cases prior to interval and consecutive screen-detected cancers from DBT + SM were due to interpretive error. METHODS: Five external breast radiologists performed the individual blinded review of 239 screening examinations (90 true negative, 39 false positive, 19 prior to interval cancer, and 91 prior to consecutive screen-detected cancer) and the informed consensus review of examinations prior to interval and screen-detected cancers (n = 110). The reviewers marked suspicious findings with a score of 1-5 (probability of malignancy). A case was false negative if ≥ 2 radiologists assigned the cancer site with a score of ≥ 2 in the blinded review and if the case was assigned as false negative by a consensus in the informed review. RESULTS: In the informed review, 5.3% of examinations prior to interval cancer and 18.7% prior to consecutive round screen-detected cancer were considered false negative. In the blinded review, 10.6% of examinations prior to interval cancer and 42.9% prior to consecutive round screen-detected cancer were scored ≥ 2. A score of ≥ 2 was assigned to 47.8% of negative and 89.7% of false positive examinations. CONCLUSIONS: The false negative rates were consistent with those of prior DM reviews, indicating that the lack of higher cancer detection for DBT + SM versus DM in the To-Be 1 trial is complex and not due to interpretive error alone. CRITICAL RELEVANCE STATEMENT: The randomized controlled trial on digital breast tomosynthesis and synthetic 2D mammograms (DBT) and digital mammography (DM), 2016-2017, showed no difference in cancer detection for the two techniques. The rates of false negative screening examinations prior to interval and consecutive screen-detected cancer for DBT were consistent with the rates in prior DM reviews, indicating that the non-superior DBT performance in the trial might not be due to interpretive error alone. KEY POINTS: • Screening with digital breast tomosynthesis (DBT) did not result in a higher breast cancer detection rate compared to screening with digital mammography (DM) in the To-Be 1 trial. • The false negative rates for examinations prior to interval and consecutive screen-detected cancer for DBT were determined in the trial to test if the lack of differences was due to interpretive error. • The false negative rates were consistent with those of prior DM reviews, indicating that the lack of higher cancer detection for DBT versus DM was complex and not due to interpretive error alone.

Overdiagnosis among women attending a population-based mammography screening program.

Increased incidence of ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC) after introduction of organized screening has prompted debate about overdiagnosis. The aim was to examine the excess in incidence of DCIS and IBC during the screening period and the deficit after women left the program, and thereby to estimate the proportion of overdiagnosis. Women invited to the Norwegian Breast Cancer Screening Program were analyzed for DCIS or IBC during the period 1995-2009. Incidence rate ratios (IRRs) were calculated for attended vs. never attended women. The IRRs were adjusted by Mantel-Haenszel (MH) method and applied to a set of reference rates and a reference population to estimate the proportion of overdiagnosis during the women's lifespan after the age of 50 years. A total of 702,131 women were invited to the program. An excess of DCIS and IBC was observed among women who attended screening during the screening period; prevalently invited women aged 50-51 years had a MH IRR of 1.86 (95% CI 1.65-2.09) and subsequently invited women aged 52-69 years had a MH IRR of 1.56 (95% CI 1.45-1.68). In women aged 70-79 years, a deficit of 30% (MH IRR 0.70, 95% CI 0.62-0.80) was observed 1-10 years after they left the screening program. The estimated proportion of overdiagnosis varied from 10 to 20% depending on outcome and whether the women were invited or actually screened. The results highlight the need for individual data with longitudinal screening history and long-term follow-up as a basis for estimating overdiagnosis.