Yit Lim

The TOMMY trial: a comparison of TOMosynthesis with digital MammographY in the UK NHS Breast Screening Programme--a multicentre retrospective reading study comparing the diagnostic performance of digital breast tomosynthesis and digital mammography with digital mammography alone.

BACKGROUND Digital breast tomosynthesis (DBT) is a three-dimensional mammography technique with the potential to improve accuracy by improving differentiation between malignant and non-malignant lesions. OBJECTIVES The objectives of the study were to compare the diagnostic accuracy of DBT in conjunction with two-dimensional (2D) mammography or synthetic 2D mammography, against standard 2D mammography and to determine if DBT improves the accuracy of detection of different types of lesions. STUDY POPULATION Women (aged 47-73 years) recalled for further assessment after routine breast screening and women (aged 40-49 years) with moderate/high of risk of developing breast cancer attending annual mammography screening were recruited after giving written informed consent. INTERVENTION All participants underwent a two-view 2D mammography of both breasts and two-view DBT imaging. Image-processing software generated a synthetic 2D mammogram from the DBT data sets. RETROSPECTIVE READING STUDY In an independent blinded retrospective study, readers reviewed (1) 2D or (2) 2D + DBT or (3) synthetic 2D + DBT images for each case without access to original screening mammograms or prior examinations. Sensitivities and specificities were calculated for each reading arm and by subgroup analyses. RESULTS Data were available for 7060 subjects comprising 6020 (1158 cancers) assessment cases and 1040 (two cancers) family history screening cases. Overall sensitivity was 87% [95% confidence interval (CI) 85% to 89%] for 2D only, 89% (95% CI 87% to 91%) for 2D + DBT and 88% (95% CI 86% to 90%) for synthetic 2D + DBT. The difference in sensitivity between 2D and 2D + DBT was of borderline significance (p = 0.07) and for synthetic 2D + DBT there was no significant difference (p = 0.6). Specificity was 58% (95% CI 56% to 60%) for 2D, 69% (95% CI 67% to 71%) for 2D + DBT and 71% (95% CI 69% to 73%) for synthetic 2D + DBT. Specificity was significantly higher in both DBT reading arms for all subgroups of age, density and dominant radiological feature (p < 0.001 all cases). In all reading arms, specificity tended to be lower for microcalcifications and higher for distortion/asymmetry. Comparing 2D + DBT to 2D alone, sensitivity was significantly higher: 93% versus 86% (p < 0.001) for invasive tumours of size 11-20 mm. Similarly, for breast density 50% or more, sensitivities were 93% versus 86% (p = 0.03); for grade 2 invasive tumours, sensitivities were 91% versus 87% (p = 0.01); where the dominant radiological feature was a mass, sensitivities were 92% and 89% (p = 0.04) For synthetic 2D + DBT, there was significantly (p = 0.006) higher sensitivity than 2D alone in invasive cancers of size 11-20 mm, with a sensitivity of 91%. CONCLUSIONS The specificity of DBT and 2D was better than 2D alone but there was only marginal improvement in sensitivity. The performance of synthetic 2D appeared to be comparable to standard 2D. If these results were observed with screening cases, DBT and 2D mammography could benefit to the screening programme by reducing the number of women recalled unnecessarily, especially if a synthetic 2D mammogram were used to minimise radiation exposure. Further research is required into the feasibility of implementing DBT in a screening setting, prognostic modelling on outcomes and mortality, and comparison of 2D and synthetic 2D for different lesion types. STUDY REGISTRATION Current Controlled Trials ISRCTN73467396. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 4. See the HTA programme website for further project information.

Accuracy of Digital Breast Tomosynthesis for Depicting Breast Cancer Subgroups in a UK Retrospective Reading Study (TOMMY Trial)

PURPOSE To compare the diagnostic performance of two-dimensional (2D) mammography, 2D mammography plus digital breast tomosynthesis (DBT), and synthetic 2D mammography plus DBT in depicting malignant radiographic features. MATERIALS AND METHODS In this multicenter, multireader, retrospective reading study (the TOMMY trial), after written informed consent was obtained, 8869 women (age range, 29-85 years; mean, 56 years) were recruited from July 2011 to March 2013 in an ethically approved study. From these women, a reading dataset of 7060 cases was randomly allocated for independent blinded review of (a) 2D mammography images, (b) 2D mammography plus DBT images, and (c) synthetic 2D mammography plus DBT images. Reviewers had no access to results of previous examinations. Overall sensitivities and specificities were calculated for younger women and those with dense breasts. RESULTS Overall sensitivity was 87% for 2D mammography, 89% for 2D mammography plus DBT, and 88% for synthetic 2D mammography plus DBT. The addition of DBT was associated with a 34% increase in the odds of depicting cancer (odds ratio [OR] = 1.34, P = .06); however, this level did not achieve significance. For patients aged 50-59 years old, sensitivity was significantly higher (P = .01) for 2D mammography plus DBT than it was for 2D mammography. For those with breast density of 50% or more, sensitivity was 86% for 2D mammography compared with 93% for 2D mammography plus DBT (P = .03). Specificity was 57% for 2D mammography, 70% for 2D mammography plus DBT, and 72% for synthetic 2D mammography plusmDBT. Specificity was significantly higher than 2D mammography (P < .001in both cases) and was observed for all subgroups (P < .001 for all cases). CONCLUSION The addition of DBT increased the sensitivity of 2D mammography in patients with dense breasts and the specificity of 2D mammography for all subgroups. The use of synthetic 2D DBT demonstrated performance similar to that of standard 2D mammography with DBT. DBT is of potential benefit to screening programs, particularly in younger women with dense breasts. (©) RSNA, 2015.

The sensitivity of pre-operative axillary staging in breast cancer: comparison of invasive lobular and ductal carcinoma.

INTRODUCTION Axillary ultrasound (AUS) with fine-needle aspiration (FNA) biopsy of abnormal lymph nodes is important for pre-operative staging and planning the surgical management of the axilla. Invasive lobular carcinoma (ILC) metastases are thought to be difficult to detect because the cells are small and on cytology resemble lymphocytes. To investigate this we directly compared the sensitivity of pre-operative axillary staging between ILC and invasive ductal carcinoma (IDC). METHOD Consecutive patients that presented in a single breast unit with pure IDC between April 2005 and December 2006 and pure ILC between January 2008 and December 2012 were retrospectively identified from pathology records. Pre-operative axillary ultrasound and FNA biopsy results were compared with post-operative histopathology from the sentinel node biopsy (SNB) or axillary lymph node dissection (ALND). RESULTS A total of 275 and 142 axillae were identified in the IDC and ILC groups respectively. In the node positive patients there was no significant difference in the sensitivity of AUS (IDC vs. ILC; 58.7% vs. 52.8%). However, there was a significant difference in the sensitivity of ultrasound-guided FNA biopsy of abnormal nodes (IDC vs. ILC; 98.4% vs. 53.6%; p < 0.001). CONCLUSION AUS has comparative sensitivities between IDC and ILC populations. In contrast, FNA biopsy of abnormal axillary nodes is clearly less sensitive in the ILC group. In these patients, who have abnormal AUS, we suggest that a core biopsy is required to improve the pre-operative staging and prevent unnecessary surgical procedures.

Does Reader Performance with Digital Breast Tomosynthesis Vary according to Experience with Two-dimensional Mammography?

Purpose To assess whether individual reader performance with digital breast tomosynthesis (DBT) and two-dimensional (2D) mammography varies with number of years of experience or volume of 2D mammograms read. Materials and Methods After written informed consent was obtained, 8869 women (age range, 29-85 years; mean age, 56 years) were recruited into the TOMMY trial (A Comparison of Tomosynthesis with Digital Mammography in the UK National Health Service Breast Screening Program), an ethically approved, multicenter, multireader, retrospective reading study, between July 2011 and March 2013. Each case was read prospectively for clinical assessment and to establish ground truth. A retrospective reading data set of 7060 cases was created and randomly allocated for independent blinded review of (a) 2D mammograms, (b) DBT images and 2D mammograms, and (c) synthetic 2D mammograms and DBT images, without access to previous examinations. Readers (19 radiologists, three advanced practitioner radiographers, and two breast clinicians) who had 3-25 (median, 10) years of experience in the U.K. National Health Service Breast Screening Program and read 5000-13 000 (median, 8000) cases per annum were included in this study. Specificity was analyzed according to reader type and years and volume of experience, and then both specificity and sensitivity were analyzed by matched inference. The median duration of experience (10 years) was used as the cutoff point for comparison of reader performance. Results Specificity improved with the addition of DBT for all readers. This was significant for all staff groups (56% vs 68% and 49% vs 67% [P < .0001] for radiologists and advanced practitioner radiographers, respectively; 46% vs 55% [P = .02] for breast clinicians). Sensitivity was improved for 19 of 24 (79%) readers and was significantly higher for those with less than 10 years of experience (91% vs 86%; P = .03) and those with total mammographic experience of fewer than 80 000 cases (88% vs 86%; P = .03). Conclusion The addition of DBT to conventional 2D screening mammography improved specificity for all readers, but the gain in sensitivity was greater for readers with less than 10 years of experience.

Digital breast tomosynthesis at screening assessment: are two views always necessary?

OBJECTIVE The current recommendation from the UK National Health Service Breast Screening Programme is that digital breast tomosynthesis (DBT) can be used for further assessment of possible screen-detected soft-tissue abnormalities in place of spot compression views and when used should be performed in two projections. The aim of the study was to assess whether two-view DBT is necessary if the abnormality is seen only in one view on initial full-field digital mammography (FFDM). METHODS 617 cases with possible masses, distortions and asymmetrical densities visualized only in one view on screening FFDM were included. All of these females underwent two-view DBT, clinical examination and ultrasound. The FFDM and DBT findings on each view were compared and correlated with the histological diagnosis. RESULTS 586 of 617 cases had normal or benign findings on further assessment, and no additional information was obtained on the other DBT view. There were 31 confirmed cancers. In 26 cases (84%), the cancer was seen on the corresponding DBT view. No cancer was seen on the other DBT view alone. Five cancers (16%) were not seen on either view on DBT owing to technical reasons. No cancers would have been missed if only the corresponding DBT view was performed. CONCLUSION Two-view DBT may not be necessary when used for further assessment of possible screen-detected soft-tissue abnormalities. Larger studies should be undertaken to investigate this further. ADVANCES IN KNOWLEDGE One-view DBT may be adequate in assessing soft-tissue abnormalities seen only on one FFDM view.

A comparison of image interpretation times in full field digital mammography and digital breast tomosynthesis

Digital Breast Tomosynthesis (DBT) provides three-dimensional images of the breast that enable radiologists to discern whether densities are due to overlapping structures or lesions. To aid assessment of the cost-effectiveness of DBT for screening, we have compared the time taken to interpret DBT images and the corresponding two-dimensional Full Field Digital Mammography (FFDM) images. Four Consultant Radiologists experienced in reading FFDM images (4 years 8 months to 8 years) with training in DBT interpretation but more limited experience (137-407 cases in the past 6 months) were timed reading between 24 and 32 two view FFDM and DBT cases. The images were of women recalled from screening for further assessment and women under surveillance because of a family history of breast cancer. FFDM images were read before DBT, according to local practice. The median time for readers to interpret FFDM images was 17.0 seconds, with an interquartile range of 12.3-23.6 seconds. For DBT, the median time was 66.0 seconds, and the interquartile range was 51.1-80.5 seconds. The difference was statistically significant (p<0.001). Reading times were significantly longer in family history clinics (p<0.01). Although it took approximately four times as long to interpret DBT than FFDM images, the cases were more complex than would be expected for routine screening, and with higher mammographic density. The readers were relatively inexperienced in DBT interpretation and may increase their speed over time. The difference in times between clinics may be due to increased throughput at assessment, or decreased density.

TOMMY Trial (a comparison of tomosynthesis with digital mammography in the UK NHS breast screening programme) setting up a multicentre imaging trial

Digital breast tomosynthesis (DBT) has the potential to improve the accuracy of standard digital mammography (DM) [1]. The TOMMY Trial is a multicentre, multireader, retrospective matched comparison of the diagnostic performance of DBT and DM.

A randomised trial of screening with digital breast tomosynthesis plus conventional digital 2D mammography versus 2D mammography alone in younger higher risk women

INTRODUCTION Digital breast tomosynthesis (DBT) has been shown to increase invasive cancer detection rates at screening compared to full field digital (2D) mammography alone, and some studies have reported a reduction in the screening recall rate. No prospective randomised studies of DBT have previously been published. This study compares recall rates with 2D mammography with and without concurrent DBT in women in their forties with a family history of breast cancer undergoing incident screening. MATERIALS AND METHODS Asymptomatic women aged 40-49 who had previously undergone mammography for an increased risk of breast cancer were recruited in two screening centres. Participants were randomised to screening with 2D mammography only at the first study screen followed a year later by screening with 2D plus DBT, or vice versa. Recall rates were compared using an intention to treat analysis. Reading performance was analysed for the larger centre. RESULTS 1227 women were recruited. 1221 first screens (604 2D, 617 2D+DBT) and 1124second screens (558 2D+DBT, 566 2D) were analysed. Eleven women had screen-detected cancers: 5 after 2D, 6 after 2D+DBT. The false positive recall rates were 2.4% for 2D and 2.2% for 2D+DBT (p=0.89). There was a significantly greater reduction between rounds in the number of women with abnormal reads who were not recalled after consensus/arbitration with 2D+DBT than 2D (p=0.023). CONCLUSION The addition of DBT to 2D mammography in incident screening did not lead to a significant reduction in recall rate. DBT may increase reader uncertainty until DBT screening experience is acquired.

Same task, same observers, different values: the problem with visual assessment of breast density

The proportion of radio-opaque fibroglandular tissue in a mammographic image of the breast is a strong and modifiable risk factor for breast cancer. Subjective, area-based estimates made by expert observers provide a simple and efficient way of measuring breast density within a screening programme, but the degree of variability may render the reliable identification of women at increased risk impossible. This study examines the repeatability of visual assessment of percent breast density by expert observers. Five consultant radiologists and two breast physicians, all with at least two years’ experience in mammographic density assessment, were presented with 100 digital mammogram cases for which they had estimated density at least 12 months previously. Estimates of percent density were made for each mammographic view and recorded on a printed visual analogue scale. The level of agreement between the two sets of estimates was assessed graphically using Bland-Altman plots. All but one observer had a mean difference of less than 6 percentage points, while the largest mean difference was 14.66 percentage points. The narrowest 95% limits of agreement for the differences were -11.15 to 17.35 and the widest were -13.95 to 40.43. Coefficients of repeatability ranged from 14.40 to 38.60. Although visual assessment of breast density has been shown to be strongly associated with cancer risk, the lack of agreement shown here between repeat assessments of the same images by the same observers questions the reliability of using visual assessment to identify women at high risk or to detect moderate changes in breast density over time.

Visual assessment of breast density using Visual Analogue Scales: observer variability, reader attributes and reading time

Breast density is a strong risk factor for breast cancer and has potential use in breast cancer risk prediction, with subjective methods of density assessment providing a strong relationship with the development of breast cancer. This study aims to assess intra- and inter-observer variability in visual density assessment recorded on Visual Analogue Scales (VAS) among trained readers, and examine whether reader age, gender and experience are associated with assessed density. Eleven readers estimated the breast density of 120 mammograms on two occasions 3 years apart using VAS. Intra- and inter-observer agreement was assessed with Intraclass Correlation Coefficient (ICC) and variation between readers visualised on Bland-Altman plots. The mean scores of all mammograms per reader were used to analyse the effect of reader attributes on assessed density. Excellent intra-observer agreement (ICC>0.80) was found in the majority of the readers. All but one reader had a mean difference of <10 percentage points from the first to the second reading. Inter-observer agreement was excellent for consistency (ICC 0.82) and substantial for absolute agreement (ICC 0.69). However, the 95% limits of agreement for pairwise differences were -6.8 to 15.7 at the narrowest and 0.8 to 62.3 at the widest. No significant association was found between assessed density and reader age, experience or gender, or with reading time. Overall, the readers were consistent in their scores, although some large variations were observed. Reader evaluation and targeted training may alleviate this problem.