Hema Purushothaman

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.

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.

Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

Background Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. Aim To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. Methods The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). Results All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1–5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. Conclusions Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging.

Does reader performance with digital breast tomosynthesis (DBT) vary with experience of 2D mammography

This work was funded by the National Institute for Health Research’s Health Technology Assessment Programme.