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Objective: To pilot a process for the independent external validation of an artificial intelligence (AI) tool to detect breast cancer using data from the NHS breast screening programme (NHSBSP). Methods: A representative data set of mammography images from 26,000 women attending 2 NHS screening centres, and an enriched data set of 2054 positive cases were used from the OPTIMAM image database. The use case of the AI tool was the replacement of the first or second human reader. The performance of the AI tool was compared to that of human readers in the NHSBSP. Results: Recommendations for future external validations of AI tools to detect breast cancer are provided. The tool recalled different breast cancers to the human readers. This study showed the importance of testing AI tools on all types of cases (including non-standard) and the clarity of any warning messages. The acceptable difference in sensitivity and specificity between the AI tool and human readers should be determined. Any information vital for the clinical application should be a required output for the AI tool. It is recommended that the interaction of radiologists with the AI tool, and the effect of the AI tool on arbitration be investigated prior to clinical use. Conclusion: This pilot demonstrated several lessons for future independent external validation of AI tools for breast cancer detection. Advances in knowledge Knowledge has been gained towards best practice procedures for performing independent external validations of AI tools for the detection of breast cancer using data from the NHS Breast Screening Programme.

OBJECTIVES: This study was designed to compare the detection of subtle lesions (calcification clusters or masses) when using the combination of digital breast tomosynthesis (DBT) and synthetic mammography (SM) with digital mammography (DM) alone or combined with DBT. METHODS: A set of 166 cases without cancer was acquired on a DBT mammography system. Realistic subtle calcification clusters and masses in the DM images and DBT planes were digitally inserted into 104 of the acquired cases. Three study arms were created: DM alone, DM with DBT and SM with DBT. Five mammographic readers located the centre of any lesion within the images that should be recalled for further investigation and graded their suspiciousness. A JAFROC figure of merit (FoM) and lesion detection fraction (LDF) were calculated for each study arm. The visibility of the lesions in the DBT images was compared with SM and DM images. RESULTS: For calcification clusters, there were no significant differences (p > 0.075) in FoM or LDF. For masses, the FoM and LDF were significantly improved in the arms using DBT compared to DM alone (p < 0.001). On average, both calcification clusters and masses were more visible on DBT than on DM and SM images. CONCLUSIONS: This study demonstrated that masses were detected better with DBT than with DM alone and there was no significant difference (p = 0.075) in LDF between DM&DBT and SM&DBT for calcifications clusters. Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses. KEY POINTS: • The detection of masses was significantly better using DBT than with digital mammography alone. • The detection of calcification clusters was not significantly different between digital mammography and synthetic 2D images combined with tomosynthesis. • Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses for the imaging technology used. ispartof: EUROPEAN RADIOLOGY vol:32 issue:2 pages:806-814 ispartof: location:Germany status: published

Funder: Policy Research Unit in Cancer Awareness, Screening and early Diagnosis, PR-PRU-1217-21601, Funder: American Cancer Society NHPDCSGBR-GBRLONG Policy Research Unit in Cancer Awareness, Screening and early Diagnosis, PR-PRU-1217-21601, BACKGROUND: This study investigates whether quantitative breast density (BD) serves as an imaging biomarker for more intensive breast cancer screening by predicting interval, and node-positive cancers. METHODS: This case-control study of 1204 women aged 47-73 includes 599 cancer cases (302 screen-detected, 297 interval; 239 node-positive, 360 node-negative) and 605 controls. Automated BD software calculated fibroglandular volume (FGV), volumetric breast density (VBD) and density grade (DG). A radiologist assessed BD using a visual analogue scale (VAS) from 0 to 100. Logistic regression and area under the receiver operating characteristic curves (AUC) determined whether BD could predict mode of detection (screen-detected or interval); node-negative cancers; node-positive cancers, and all cancers vs. controls. RESULTS: FGV, VBD, VAS, and DG all discriminated interval cancers (all p < 0.01) from controls. Only FGV-quartile discriminated screen-detected cancers (p < 0.01). Based on AUC, FGV discriminated all cancer types better than VBD or VAS. FGV showed a significantly greater discrimination of interval cancers, AUC = 0.65, than of screen-detected cancers, AUC = 0.61 (p < 0.01) as did VBD (0.63 and 0.53, respectively, p < 0.001). CONCLUSION: FGV, VBD, VAS and DG discriminate interval cancers from controls, reflecting some masking risk. Only FGV discriminates screen-detected cancers perhaps adding a unique component of breast cancer risk.

Objectives In breast cancer screening, two readers separately examine each woman’s mammograms for signs of cancer. We examined whether preventing the two readers from seeing each other’s decisions (blinding) affects behaviour and outcomes. Methods This cohort study used data from the CO-OPS breast-screening trial (1,119,191 women from 43 screening centres in England) where all discrepant readings were arbitrated. Multilevel models were fitted using Markov chain Monte Carlo to measure whether reader 2 conformed to the decisions of reader 1 when they were not blinded, and the effect of blinding on overall rates of recall for further tests and cancer detection. Differences in positive predictive value (PPV) were assessed using Pearson’s chi-squared test. Results When reader 1 recalls, the probability of reader 2 also recalling was higher when not blinded than when blinded, suggesting readers may be influenced by the other’s decision. Overall, women were less likely to be recalled when reader 2 was blinded (OR 0.923; 95% credible interval 0.864, 0.986), with no clear pattern in cancer detection rate (OR 1.029; 95% credible interval 0.970, 1.089; Bayesian p value 0.832). PPV was 22.1% for blinded versus 20.6% for not blinded (p < 0.001). Conclusions Our results suggest that when not blinded, reader 2 is influenced by reader 1’s decisions to recall (alliterative bias) which would result in bypassing arbitration and negate some of the benefits of double-reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics. Key Points • In Europe, it is recommended that breast screening mammograms are analysed by two readers but there is little evidence on the effect of ‘blinding’ the readers so they cannot see each other’s decisions. • We found evidence that when the second reader is not blinded, they are more likely to agree with a recall decision from the first reader and less likely to make an independent judgement (alliterative error). This may reduce overall accuracy through bypassing arbitration. • This observational study suggests an association between blinding the second reader and higher positive predictive value of screening, but this may be confounded by centre characteristics.

Background The Sloane audit compares screen-detected ductal carcinoma in situ (DCIS) pathology with subsequent management and outcomes. Methods This was a national, prospective cohort study of DCIS diagnosed during 2003–2012. Results Among 11,337 patients, 7204 (64%) had high-grade DCIS. Over time, the proportion of high-grade disease increased (from 60 to 65%), low-grade DCIS decreased (from 10 to 6%) and mean size increased (from 21.4 to 24.1 mm). Mastectomy was more common for high-grade (36%) than for low-grade DCIS (15%). Few (6%) patients treated with breast-conserving surgery (BCS) had a surgical margin n = 413), median time 62 months, followed by DCIS (n = 225), at median 37 months. Radiotherapy (RT) was most protective against recurrence for high-grade DCIS (3.2% for high-grade DCIS with RT compared to 6.9% without, compared with 2.3 and 3.0%, respectively, for low/intermediate-grade DCIS). Ipsilateral DCIS events lessened after 5 years, while the risk of ipsilateral invasive cancer remained consistent to beyond 10 years. Conclusion DCIS pathology informs patient management and highlights the need for prolonged follow-up of screen-detected DCIS.

Introduction This multicentre, retrospective study aimed to establish correlation between estimated tumour volume doubling times (TVDT) from a series of interval breast cancers with their clinicopathological features. The potential impact of delayed diagnosis on prognosis was also explored. Materials and methods Interval cancers, where screening mammograms demonstrated changes that were retrospectively classified as either uncertain or suspicious, were reviewed from five screening units within the UK NHS Breast Screening Programme (NHSBSP). Data collected included the time interval between screening mammogram and cancer diagnosis, the size of the initial mammographic abnormality and of the subsequent cancer, demographics, mammographic density and tumour biology. We estimated volume doubling times and the estimated change in size and node status, which would have followed if these cancers had been detected at the previous screen. Results 306 interval cancers meeting the inclusion criteria were identified. Average time from screening to diagnosis was 644 days (SD 276 days). 19% were diagnosed in the first twelve months, 42% in the subsequent twelve months and 39% thereafter. Overall average estimated TVDT was 167 days (95% CI 151–186). Significant differences were noted with age (p = 0.01), grade (p, Highlights • Unfavourable tumour grade and ER negativity were associated with shorter duration tumour volume doubling time. • Delayed diagnosis of the interval cancers in this series was estimated to reduce ten year survival from 86% to 82%. • Breast cancers in younger women were estimated to display faster growth, i.e., shorter doubling time.

IntroductionThe National Health Service (NHS) Breast Screening Programme aims to detect cancer earlier when treatment is more effective but can harm women by over diagnosing and overtreating cancers which would never have become symptomatic. As well as breast cancer, a spectrum of atypical epithelial proliferations (atypia) can also be detected as part of screening. This spectrum of changes, while not cancer, may mean that a woman is more likely to develop breast cancer in the future. Follow-up of atypia is not evidence based. We currently do not know which atypia should be detected to avoid future cancer. This study will explore how atypia develops into breast cancer in terms of number of women, time of cancer development, cancer type and severity, and whether this varies for different types of atypia.Methods and analysisThe Sloane cohort study began in April 2003 with ongoing data collection including atypia diagnosed through screening at screening units in the UK. The database for England has 3645 cases (24 September 2020) of epithelial atypia, with follow-up from 1 to 15 years. The outcomes include subsequent invasive breast cancer and the nature of subsequent cancer. Descriptive statistics will be produced. The observed rates of breast cancer at 1, 3 and 6 years for types of atypia will be reported with CIs, to enable comparison to women in the general population. Time to event methods will be used to describe the time to breast cancer diagnosis for the types of atypia, including flexible parametric modelling if appropriate. Patient representatives from Independent Cancer Patients’ Voice are included at every stage of the research.Ethics and disseminationThe study has received research ethics approval from the University of Warwick Biomedical and Scientific Research Ethics Committee (BSREC 10/20–21, 8 October 2020), Public Health England office for data release approvals (ODR1718_313) and approval from the English Breast Research Advisory Committee (BSPRAC_031). The findings will be disseminated to breast screening clinicians (via journal publication and conference presentation), to the NHS Breast Screening Programme to update their guidelines on how women with atypia should be followed up, and to the general public.

Peer reviewed: True, PURPOSE: The introduction of breast screening in the UK led to an increase in the detection of non-invasive breast neoplasia, predominantly ductal carcinoma in situ (DCIS), a non-obligatory precursor of invasive breast cancer. The Sloane Project, a UK prospective cohort study of screen-detected non-invasive breast neoplasia, commenced in 2003 to evaluate the radiological assessment, surgical management, pathology, adjuvant therapy and outcomes for non-invasive breast neoplasia. Long-term follow-up and accurate data collection are essential to examine the clinical impact. Here, we describe the establishment, development and analytical processes for this large UK cohort study. PARTICIPANTS: Women diagnosed with non-invasive breast neoplasia via the UK National Health Service Breast Screening Programme (NHSBSP) from 01 April 2003 are eligible, with a minimum age of 46 years. Diagnostic, therapeutic and follow-up data collected via proformas, complement date and cause of death from national data sources. Accrual for patients with DCIS ceased in 2012 but is ongoing for patients with epithelial atypia/in situ neoplasia, while follow-up for all continues long term. FINDINGS TO DATE: To date, patients within the Sloane cohort comprise one-third of those diagnosed with DCIS within the NHSBSP and are representative of UK practice. DCIS has a variable outcome and confirms the need for longer-term follow-up for screen-detected DCIS. However, the radiology and pathology features of DCIS can be used to inform patient management. We demonstrate validation of follow-up information collected from national datasets against traditional, manual methods. FUTURE PLANS: Conclusions derived from the Sloane Project are generalisable to women in the UK with screen-detected DCIS. The follow-up methodology may be extended to other UK cohort studies and routine clinical follow-up. Data from English patients entered into the Sloane Project are available on request to researchers under data sharing agreement. Annual follow-up data collection will continue for a minimum of 20 years.

Objectives To study how radiologists’ perceived ability to interpret digital mammography (DM) images is affected by decreases in image quality. Methods One view from 45 DM cases (including 30 cancers) was degraded to six levels each of two acquisition-related issues (lower spatial resolution and increased quantum noise) and three post-processing-related issues (lower and higher contrast and increased correlated noise) seen during clinical evaluation of DM systems. The images were shown to fifteen breast screening radiologists from five countries. Aware of lesion location, the radiologists selected the most-degraded mammogram (indexed from 1 (reference) to 7 (most degraded)) they still felt was acceptable for interpretation. The median selected index, per degradation type, was calculated separately for calcification and soft tissue (including normal) cases. Using the two-sided, non-parametric Mann-Whitney test, the median indices for each case and degradation type were compared. Results Radiologists were not tolerant to increases (medians: 1.5 (calcifications) and 2 (soft tissue)) or decreases (median: 2, for both types) in contrast, but were more tolerant to correlated noise (median: 3, for both types). Increases in quantum noise were tolerated more for calcifications than for soft tissue cases (medians: 3 vs. 4, p = 0.02). Spatial resolution losses were considered less acceptable for calcification detection than for soft tissue cases (medians: 3.5 vs. 5, p = 0.001). Conclusions Perceived ability of radiologists for image interpretation in DM was affected not only by image acquisition-related issues but also by image post-processing issues, and some of those issues affected calcification cases more than soft tissue cases. Key Points • Lower spatial resolution and increased quantum noise affected the radiologists’ perceived ability to interpret calcification cases more than soft tissue lesion or normal cases. • Post-acquisition image processing-related effects, not only image acquisition-related effects, also impact the perceived ability of radiologists to interpret images and detect lesions. • In addition to current practices, post-acquisition image processing-related effects need to also be considered during the testing and evaluation of digital mammography systems.

Background Artificial intelligence (AI) systems performing at radiologist-like levels in the evaluation of digital mammography (DM) would improve breast cancer screening accuracy and efficiency. We aimed to compare the stand-alone performance of an AI system to that of radiologists in detecting breast cancer in DM. Methods Nine multi-reader, multi-case study datasets previously used for different research purposes in seven countries were collected. Each dataset consisted of DM exams acquired with systems from four different vendors, multiple radiologists’ assessments per exam, and ground truth verified by histopathological analysis or follow-up, yielding a total of 2652 exams (653 malignant) and interpretations by 101 radiologists (28 296 independent interpretations). An AI system analyzed these exams yielding a level of suspicion of cancer present between 1 and 10. The detection performance between the radiologists and the AI system was compared using a noninferiority null hypothesis at a margin of 0.05. Results The performance of the AI system was statistically noninferior to that of the average of the 101 radiologists. The AI system had a 0.840 (95% confidence interval [CI] = 0.820 to 0.860) area under the ROC curve and the average of the radiologists was 0.814 (95% CI = 0.787 to 0.841) (difference 95% CI = −0.003 to 0.055). The AI system had an AUC higher than 61.4% of the radiologists. Conclusions The evaluated AI system achieved a cancer detection accuracy comparable to an average breast radiologist in this retrospective setting. Although promising, the performance and impact of such a system in a screening setting needs further investigation.

To develop methods to model the relationship between cancer detection and recall rates to inform professional standards. Annual screening programme information for each of the 80 English NHSBSP units (totalling 11.3 million screening tests) for the seven screening years from 1 April 2009 to 31 March 2016 and some Dutch screening programme information were used to produce linear and non-linear models. The non-linear models estimated the modelled maximum values (MMV) for cancers detected at different grades and estimated how rapidly the MMV was reached (the modelled ‘slope’ (MS)). Main outcomes include the detection rate for combined invasive/micro-invasive and high-grade DCIS (IHG) detection rate and the low/intermediate grade DCIS (LIG) detection rate. At prevalent screens for IHG cancers, 99% of the MMV was reached at a recall rate of 7.0%. The LIG detection rate had no discernible plateau, increasing linearly at a rate of 0.12 per 1000 for every 1% increase in recall rate. At incident screens, 99% of the MMV for IHG cancer detection was 4.0%. LIG DCIS increased linearly at a rate of 0.18 per 1000 per 1% increase in recall rate. Our models demonstrate the diminishing returns associated with increasing recall rates. The screening programme in England could use the models to set recall rate ranges, and other countries could explore similar methodology. • Question: How can we determine optimum recall rates in breast cancer screening? • Findings: In this large observational study, we show that increases in recall rates above defined levels are almost exclusively associated with false positive recalls and a very small increase in low/intermediate grade DCIS. • Meaning: High recall rates are not associated with increases in detection of life-threatening cancers. The models developed in this paper can be used to help set recall rate ranges that maximise benefit and minimise harm.

Purpose To study the feasibility of automatically identifying normal digital mammography (DM) exams with artificial intelligence (AI) to reduce the breast cancer screening reading workload. Methods and materials A total of 2652 DM exams (653 cancer) and interpretations by 101 radiologists were gathered from nine previously performed multi-reader multi-case receiver operating characteristic (MRMC ROC) studies. An AI system was used to obtain a score between 1 and 10 for each exam, representing the likelihood of cancer present. Using all AI scores between 1 and 9 as possible thresholds, the exams were divided into groups of low- and high likelihood of cancer present. It was assumed that, under the pre-selection scenario, only the high-likelihood group would be read by radiologists, while all low-likelihood exams would be reported as normal. The area under the reader-averaged ROC curve (AUC) was calculated for the original evaluations and for the pre-selection scenarios and compared using a non-inferiority hypothesis. Results Setting the low/high-likelihood threshold at an AI score of 5 (high likelihood > 5) results in a trade-off of approximately halving (− 47%) the workload to be read by radiologists while excluding 7% of true-positive exams. Using an AI score of 2 as threshold yields a workload reduction of 17% while only excluding 1% of true-positive exams. Pre-selection did not change the average AUC of radiologists (inferior 95% CI > − 0.05) for any threshold except at the extreme AI score of 9. Conclusion It is possible to automatically pre-select exams using AI to significantly reduce the breast cancer screening reading workload., European Radiology, 29 (9), ISSN:0938-7994, ISSN:1432-1084

ObjectiveRandomised controlled trials have shown a reduction in breast cancer mortality from mammography screening and it is the detection of high-grade invasive cancers that is responsible for much of this effect. We determined the detection rates of invasive cancers by grade, size and type of screen and estimated relative sensitivities with emphasis on grade 3 detection.MethodsThis observational study analysed data from over 11 million screening episodes (67,681 invasive cancers) from the English NHS breast screening programme over seven screening years 2009/2010 to 2015/2016 for women aged 45–70.ResultsAt prevalent (first) screens (which are unaffected by screening interval), the detection rate of small (ConclusionsSensitivity for small grade 3 invasive cancers is poor compared with that for grade 1 and 2 invasive cancers and larger grade 3 malignancies. This observation is likely a limitation of the current technology related to the absence of identifiable mammographic features for small high-grade cancers. Future work should focus on technologies and strategies to improve detection of these clinically most significant cancers.Key Points• The detection of small high-grade invasive cancers is vital to reduce breast cancer mortality.• We estimate the sensitivity for small grade 3 invasive cancers may be only 26% of that of small grade 1 invasive cancers. This is likely to be associated with the non-specific mammographic features for these cancers.• New technologies and appropriate strategies using current technology are required to maximise the detection of small grade 3 invasive cancers.

This study was designed to compare the detection of subtle lesions (calcification clusters or masses) when using the combination of digital breast tomosynthesis (DBT) and synthetic mammography (SM) with digital mammography (DM) alone or combined with DBT.A set of 166 cases without cancer was acquired on a DBT mammography system. Realistic subtle calcification clusters and masses in the DM images and DBT planes were digitally inserted into 104 of the acquired cases. Three study arms were created: DM alone, DM with DBT and SM with DBT. Five mammographic readers located the centre of any lesion within the images that should be recalled for further investigation and graded their suspiciousness. A JAFROC figure of merit (FoM) and lesion detection fraction (LDF) were calculated for each study arm. The visibility of the lesions in the DBT images was compared with SM and DM images.For calcification clusters, there were no significant differences (p0.075) in FoM or LDF. For masses, the FoM and LDF were significantly improved in the arms using DBT compared to DM alone (p0.001). On average, both calcification clusters and masses were more visible on DBT than on DM and SM images.This study demonstrated that masses were detected better with DBT than with DM alone and there was no significant difference (p = 0.075) in LDF between DMDBT and SMDBT for calcifications clusters. Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses.• The detection of masses was significantly better using DBT than with digital mammography alone. • The detection of calcification clusters was not significantly different between digital mammography and synthetic 2D images combined with tomosynthesis. • Our results support previous studies that it may be acceptable to not acquire digital mammography alongside tomosynthesis for subtle calcification clusters and ill-defined masses for the imaging technology used.

To review outcomes of male patients attending the breast unit, evaluate effectiveness of imaging and examination in detecting breast cancer and review adherence to guidelines for male breast imaging.A retrospective review was undertaken of male patients attending Cambridge Breast Unit from 1 January 2015 to 31 December 2019. Patient electronic records and imaging were reviewed to establish demographics, clinical findings, imaging, biopsy, and pathology outcomes.Of 1,362 male patients attending the breast unit, 1,028 (75%) had imaging performed. Biopsy was performed in 41 men (3%), with 14 cancers diagnosed (1%). Clinical examination showed 42.7% sensitivity, 99.6% specificity, 54.6% positive predictive value (PPV) and 99.4% negative predictive value (NPV) for detection of cancer. Mammogram demonstrated 84.6% sensitivity, 99.4% specificity, 69.8% PPV, and 99.8% NPV for detection of malignancy. Ultrasound demonstrated 78.6% sensitivity, 98.9% specificity, 73.3% PPV and 99.2% NPV for detection of cancer. Forty-one percent of patients40 years and 51% 50 years were imaged, who according to local and Royal College of Radiologists (RCR) guidelines did not require imaging based on age and clinical score.Male patients account for a small proportion of referrals to the breast unit but generate significant workload. Imaging protocols, incorporating clinical score and age cut-off at 40 years remains robust for detecting malignancy. Clinician awareness of the imaging protocol, and close liaison with radiologists is essential to minimise additional radiology workload.

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. In mammography, measurement of breast density, dose estimation, and differentiation between cysts and solid tumours are example applications requiring accurate data on tissue attenuation. Published attenuation data are, however, sparse and cover a relatively wide range. To supplement available data we have previously measured the attenuation of cyst fluid and solid lesions using photon-counting spectral mammography. The present study aims to measure the attenuation of normal adipose and glandular tissue, and to measure the effect of formalin fixation, a major uncertainty in published data. A total of 27 tumour specimens, 7 fibro-glandular tissue specimens, and 15 adipose tissue specimens were included. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, from which x-ray attenuation as a function of energy can be derived. The spread in attenuation between samples was relatively large, partly because of natural variation. The variation of malignant and glandular tissue was similar, whereas that of adipose tissue was lower. Formalin fixation slightly altered the attenuation of malignant and glandular tissue, whereas the attenuation of adipose tissue was not significantly affected. The difference in attenuation between fresh tumour tissue and cyst fluid was smaller than has previously been measured for fixed tissue, but the difference was still significant and discrimination of these two tissue types is still possible. The difference between glandular and malignant tissue was close-to significant; it is reasonable to expect a significant difference with a larger set of samples. We believe that our studies have contributed to lower the overall uncertainty of breast tissue attenuation in the literature due to the relatively large sample sets, the novel measurement method, and by clarifying the difference between fresh and fixed tissue. QC 20210108

Knowledge of x-ray attenuation is essential for developing and evaluating x-ray imaging technologies. For instance, techniques to better characterize cysts at mammography screening would be highly desirable to reduce recalls, but the development is hampered by the lack of attenuation data for cysts. We have developed a method to measure x-ray attenuation of tissue samples using a prototype photon-counting spectral mammography unit. The method was applied to measure the attenuation of 50 samples of breast cyst fluid and 50 samples of water. Spectral (energy-resolved) images of the samples were acquired and the image signal was mapped to equivalent thicknesses of two known reference materials, which can be used to derive the x-ray attenuation as a function of energy. The attenuation of cyst fluid was found to be significantly different from water. There was a relatively large natural spread between different samples of cyst fluid, whereas the homogeneity of each individual sample was found to be good; the variation within samples did not reach above the quantum noise floor. The spectral method proved stable between several measurements on the same sample. Further, chemical analysis and elemental attenuation calculation were used to validate the spectral measurement on a subset of the samples. The two methods agreed within the precision of the elemental attenuation calculation over the mammographic energy range., Comment: arXiv admin note: substantial text overlap with arXiv:2101.02449

The development of new x-ray imaging techniques often requires prior knowledge of tissue attenuation, but the sources of such information are sparse. We have measured the attenuation of adipose breast tissue using spectral imaging, in vitro and in vivo. For the in-vitro measurement, fixed samples of adipose breast tissue were imaged on a spectral mammography system, and the energy-dependent x-ray attenuation was measured in terms of equivalent thicknesses of aluminum and poly-methyl methacrylate (PMMA). For the in-vivo measurement, a similar procedure was applied on a number of spectral screening mammograms. The results of the two measurements agreed well and were consistent with published attenuation data and with measurements on tissue-equivalent material., Comment: arXiv admin note: text overlap with arXiv:2101.02449

Contains fulltext : 229548.pdf (Publisher’s version ) (Open Access) PURPOSE: To develop a candidate instrument to assess image quality in digital mammography, by identifying clinically relevant features in images that are affected by lower image quality. METHODS: Interviews with fifteen expert breast radiologists from five countries were conducted and analysed by using adapted directed content analysis. During these interviews, 45 mammographic cases, containing 44 lesions (30 cancers, 14 benign findings), and 5 normal cases, were shown with varying image quality. The interviews were performed to identify the structures from breast tissue and lesions relevant for image interpretation, and to investigate how image quality affected the visibility of those structures. The interview findings were used to develop tentative items, which were evaluated in terms of wording, understandability, and ambiguity with expert breast radiologists. The relevance of the tentative items was evaluated using the content validity index (CVI) and modified kappa index (k*). RESULTS: Twelve content areas, representing the content of image quality in digital mammography, emerged from the interviews and were converted into 29 tentative items. Fourteen of these items demonstrated excellent CVI>/=0.78 (k* > 0.74), one showed good CVI

In this study we used a large previously built database of 2,892 mammograms and 31,650 single mammogram radiologists’ assessments to simulate the impact of replacing one radiologist by an AI system in a double reading setting. The double human reading scenario and the double hybrid reading scenario (second reader replaced by an AI system) were simulated via bootstrapping using different combinations of mammograms and radiologists from the database. The main outcomes of each scenario were sensitivity, specificity and workload (number of necessary readings). The results showed that when using AI as a second reader, workload can be reduced by 44%, sensitivity remains similar (difference -0.1%; 95% CI = - 4.1%, 3.9%), and specificity increases by 5.3% (P

The OPTIMAM Mammography Image Database is a sharable resource with processed and unprocessed mammography images from United Kingdom breast screening centers, with annotated cancers and clinical det...

We summarise here the information to be provided to women and referring physicians about percutaneous breast biopsy and lesion localisation under imaging guidance. After explaining why a preoperative diagnosis with a percutaneous biopsy is preferred to surgical biopsy, we illustrate the criteria used by radiologists for choosing the most appropriate combination of device type for sampling and imaging technique for guidance. Then, we describe the commonly used devices, from fine-needle sampling to tissue biopsy with larger needles, namely core needle biopsy and vacuum-assisted biopsy, and how mammography, digital breast tomosynthesis, ultrasound, or magnetic resonance imaging work for targeting the lesion for sampling or localisation. The differences among the techniques available for localisation (carbon marking, metallic wire, radiotracer injection, radioactive seed, and magnetic seed localisation) are illustrated. Type and rate of possible complications are described and the issue of concomitant antiplatelet or anticoagulant therapy is also addressed. The importance of pathological-radiological correlation is highlighted: when evaluating the results of any needle sampling, the radiologist must check the concordance between the cytology/pathology report of the sample and the radiological appearance of the biopsied lesion. We recommend that special attention is paid to a proper and tactful approach when communicating to the woman the need for tissue sampling as well as the possibility of cancer diagnosis, repeat tissue sampling, and or even surgery when tissue sampling shows a lesion with uncertain malignant potential (also referred to as “high-risk” or B3 lesions). Finally, seven frequently asked questions are answered.

Key words: DCIS, radiotherapy, endocrine therapy, survival, surgical margins Background: The benefits and risks of breast screening remain controversial, with particular concern that ductal carcinoma in situ (DCIS) may be over-diagnosed and over-treated. There is little prospective data on treatment or outcomes for screen detected DCIS. Methods: A prospective cohort of non-invasive lesions diagnosed through the United Kingdom National Health Service Breast Screening Programme (NHSBSP) (1 April 2003 to 31 March 2012) was linked to national databases and case note review to analyse patterns of care, recurrence and mortality. Results: Screen-detected DCIS in 9938 women was analysed, 33% (9938/30041) of women with a final diagnosis of non-invasive breast neoplasia diagnosed through the NHSBSP over the same time. The patients (mean age was 60 years: range 46-87 years) were treated by breast conservation surgery (BCS; 7007; 70.5%) or mastectomy (2931). At 64 months median follow up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or mastectomy (4.5%) (p Breast radiotherapy (RT) after BCS (4363/7007; 62%) was associated with a 3.1% absolute reduction in any ipsilateral DCIS or invasive cancer (No RT: 7.2% vs RT: 4.1% (p Among 321 (3.2%) women who died, 46 deaths (0.5%; 14.3% of all deaths) were attributed to invasive breast cancer. Death from breast cancer was uncommon and outnumbered 5:1 by death due to other causes. RT after BCS was associated with a non-significant 0.2% absolute reduction in breast cancer mortality. However, women who developed invasive breast cancer had a worse survival than those with further DCIS (p Conclusions: Recurrent DCIS or invasive cancer is uncommon following screen detected DCIS treated by surgery and adjuvant therapy. Both RT and endocrine therapy following surgery were associated with a significant reduction in further DCIS and invasive disease, but not breast cancer mortality, within 5 years of diagnosis. This study quantifies the benefits of radiotherapy and endocrine therapy to inform decision making in the management of screen detected DCIS. Citation Format: Thompson AM, Clements K, Cheung S, Pinder SE, Lawrence G, Sawyer E, Kearins O, Ball GR, Tomlinson I, Hanby AM, Thomas J, Maxwell AJ, Wallis MG, Dodwell DJ. Impact of radiotherapy and endocrine therapy on further events: Final multivariate analysis of a prospective, national cohort study of screen detected ductal carcinoma in situ (DCIS) of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-02.

Background: LORIS is a multi-centre, randomised (1:1) controlled trial of Surgery v Active Monitoring with annual mammography in patients with low risk ductal carcinoma in situ (DCIS). During a 2 year Feasibility Study potential patients were invited to complete the Clinical Trials Questionnaire (CTQ)1 and participate in a semi structured telephone interview about the verbal, written and DVD based trial information. The DVD was produced to complement the patient information sheet (PIS) and incorporates simple graphics and a Q&A session with women asking the Chief Investigator questions about the trial. Aims:To examine the reasons for trial participation/rejection and obtain feedback about the clarity, timing and usefulness of the PIS and DVD in order to identify potential communication drivers and barriers to trial recruitment. Methods: Participants completed the CTQ1 prior to randomisation and with their consent were contacted following randomisation for an interview. Women declining the trial were issued with an optional pack containing the CTQ1 and the researchers' contact details if they wanted an interview. The CTQ1 comprises16 reasons that might influence a decision to either accept or decline a trial. For each statement participants register their agreement or disagreement on a scale of 1 (strongly agree) to 5 (strongly disagree) and indicate the most important reason for their decision. Interviews explored factors such as, attitudes about randomisation, and usefulness of the trial information provided. Results: 41 patients were randomised during feasibility; 20 surgery, 21 active monitoring, 16 patients declined the trial. 40/41(98%) acceptors and 9/16 (56%) decliners completed the CTQ1. The main reason for joining LORIS was:- “I thought the trial offered the best treatment available” 13/40 (32%) and for decling the trial was “The idea of randomisation worried me” (4/9; 44%). 35 interviews were conducted (31/41 (76%) accepted and 4/16 (25%) declined LORIS). At interview acceptors commented that the PIS was very useful and clear (84%; 26/31 & 90%; 28/31, respectively). 74% (23/31) of women who joined LORIS watched the DVD and the majority (19/23; 83%) found it “very useful” and 22 (22/23; 96%) “very easy to understand”. A third of women (10/31) said the PIS and the DVD helped them decide to participate in LORIS. Women who declined the trial had clear treatment preferences; 2/4 did not watch the DVD. Three quarters of women interviewed (19/25) watched the DVD with family members/friends and found it reassuring. One commented it was “Put in words you can understand and not be baffled by”. The most popular aspect was the Q&A session (13/25; 52%). Conclusions:The LORIS DVD was a useful, easy to understand recruitment tool, complementing the PIS. Many women felt reassured that the content was consistent with, and added to that provided by healthcare professionals. Opinions of family and friends, worries about randomisation and personal preferences exert an influence of those declining these types of trial. Fallowfield LJ, Jenkins V, et al. (1998) Attitudes of patients to randomised clinical trials of cancer therapy. Eur J Cancer 34(10):1554–1559. Citation Format: Fallowfield LJ, Matthews L, Jenkins VA, May SF, Francis A, Rae D, Wallis M. Interview data from women contemplating LORIS trial entry during the feasibility study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-08-01.

Breast cancer screening with mammography reduces mortality in the women who attend by detecting high risk cancer early. It is far from perfect with variations in both sensitivity for the detection of cancer and very wide variations in specificity, leading to unnecessary recalls and biopsies. Over the last 12 months several papers have reported on AI algorithms that perform as well as human readers on large well curated population data sets. The nature of the test sets, the way the gold standard has been calculated, the definition of a positive call, and the statistics used all influence the results. Historically retrospective studies have not predicted the real-life performance of radiologist plus machine. So, it is important to perform prospective studies before introducing Artificial intelligence into real world breast screening.

Introduction:\ud Optimum mammography positioning technique is necessary to maximise cancer detection. Current criteria for mammography appraisal lack reliability and validity with a need to develop a more objective system.\ud \ud We aimed to establish current international practice in assessing image quality (IQ), of screening mammograms then develop and validate a reproducible assessment tool.\ud \ud Methods:\ud A questionnaire sent to centres in countries undertaking population screening identified practice, participants for an expert panel (EP) of radiologists/radiographers and a testing panel (TP) of radiographers. The EP developed category criteria and descriptors using a modified Delphi process to agree definitions.\ud \ud The EP scored 12 screening mammograms to test agreement then a main set of 178 cases. Weighted scores were derived for each descriptor enabling calculation of numerical parameters for each new category. The TP then scored the main set. Statistical analysis included ANOVA, t-tests and Kendall's coefficient.\ud \ud Results:\ud 11 centres in 8 countries responded forming an EP of 7 members and TP of 44 members.\ud \ud The EP showed moderate agreement when the scoring the mini test set W = 0.50 p < 0.001 and the main set W = 0.55 p < 0.001, ‘posterior nipple line’ being the most difficult descriptor.\ud \ud The weighted total scores differentiated the 4 new categories Perfect, Good, Adequate and Inadequate (p < 0.001).\ud \ud Conclusion:\ud We have developed an assessment tool by Delphi consensus and weighted consensus criteria. We have successfully tabulated a range of numerical scores for each new category providing the first validated and reproducible mammography IQ scoring system.

Aims To assess the feasibility of undertaking microbubble-guided vacuum-assisted biopsy (VAB) of the sentinel lymph node (SLN) and determine its sensitivity in detecting metastases. Patient experience and the impact of VAB on subsequent axillary surgery were also evaluated. Materials and methods Patients with a normal axillary ultrasound or benign core biopsy planned for surgical SLN biopsy were recruited. Part 1 of the study was used to establish the technique of ultrasound microbubble contrast to detect the SLN. In Part 2 microbubble detection of the SLN was followed by 13 G VAB. All patients subsequently had surgical histological correlation. Results One hundred and thirty-nine patients were recruited: 36 to Part 1 and 103 to Part 2. Of the 100 patients in Part 2 included for analysis, 82 (82%) underwent successful biopsy. Sensitivity for detecting metastases was 58.8% (95% confidence interval: 32.9%, 81.6%). The procedure was generally well tolerated; however, VAB interfered adversely with subsequent surgical SLN biopsy with surgeons reporting moderate or severe interference in 48% of patients and an additional 8.3% with complete failure of SLNB. Conclusion It is possible to perform VAB of microbubble-detected SLNs. Although the sensitivity for detecting metastases was reasonable, the adverse effect on subsequent surgery was significant.

Purpose In patients with breast cancer, avoiding overtreatment of the axilla without compromising oncological outcomes is an important clinical goal. Previous work has suggested that patients with a normal grey-scale ultrasound and benign radiological core biopsy of SLN identified with CEUS are unlikely to have high volume axillary metastases. We therefore assessed the reproducibility of this biopsy technique in multiple centres and in 2 centres, measured the volume of axillary metastases at the end of primary surgical treatment in patients with a false negative SLN core biopsy. Materials and Methods Between 2010 and 2016 data were collected on patients with early breast cancer; 1361 from Maidstone Breast Clinic (1) (prospective, sequential), 376 from Tunbridge Wells Breast Clinic (2) (retrospective, sequential), 122 from Leeds Breast Clinic (3) (retrospective, selected) and 48 from Imperial College Healthcare (4) (prospective, selected). Patients at Centres 1 and 2 had a normal grey-scale axillary ultrasound. Patients had a CEUS SLN core biopsy procedure prior to axillary surgery (sentinel lymph node excision (SLNE)/axillary lymph node dissection (ALND)). Results SLN were successfully core biopsied (nodal tissue retrieved) in 80% (Centre 1), 79.5% (Centre 2), 77.5% (Centre 3) and 88% (Centre 4). Patients with invasive breast cancer and a successful SLN core biopsy went on to have primary surgical treatment, 816 (Centre 1), 215 (Centre 2), 80 (Centre 3) and 38 (Centre 4). As a test to identify all SLN metastases, the sensitivities were 47.5% (95% CI 39.9-55.1), 52.5% (95% CI 39.1-65.7), 46.4% (95% CI 27.5-66.1) and 45.5% (95% CI 16.7-76.6) respectively. Specificities; 99.7% (95% CI 98.9-100), 98.1 (95% CI 94.5-99.6), 100% (95% CI 93.2-100%) and 96.3% (95% CI 81-99.9) respectively. Negative predictive values; 87.3% (95% CI 84.6-89.6), 84.5% (95% CI 78.4-89.5), 86.9% (95% CI 82.4-90.3) and 86.2% (95% CI 78.4-91.5) respectively. At Centres 1 and 2, 13/637 (2%) and 6/183 (3%) respectively of patients with a benign microbubble/ CEUS SLN core biopsy had 2 or more LN macrometastases found at SLNE/ ALND. Conclusion The identification and biopsy of SLN using CEUS is a reproducible technique. Despite the low sensitivity, the negative predictive value is high and in a large cohort of patients from centres 1 and 2, only a small proportion of patients had 2 or more 2 lymph node macro metastases that were both occult on grey-scale ultrasound and missed by SLN core biopsy. In the era of axillary conservation, these results indicate that some patients may be suitable for complete radiological staging of the axilla and thus safely avoid axillary surgery. Citation Format: Cox KL, Sharma N, Taylor-Phillips S, Weeks J, Mills P, Lim A, Haigh I, Sever A, Wallis M, DeSilva T, Hashem M. Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound (CEUS) to identify and biopsy sentinel lymph nodes (SLN) in breast cancer is a reproducible technique and may characterise a group of patients who can completely avoid axillary surgery [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-04.

Background: Fat necrosis is a common finding after trauma or surgery of the breast. There are various presentations on imaging and differentiation from malignancy can be challenging. Objectives: To analyze early signs of fat necrosis on postoperative mammograms after the excision of benign and malignant findings in accordance to modern adjuvant treatment. Patients and Methods: A retrospective analysis was performed as part of an audit. Mammograms of 39 patients, who underwent surgical excision of benign disease, and 81 patients with cancer surgery, were reviewed. Adjuvant therapy, such as radiotherapy, chemotherapy and hormonal treatment, was noted. Results: Mean patient age was 54.6 ± 6.5 years in the benign and 59.8 ± 7.8 years in the malignant group. Mean lesion size did not differ between the groups (P = 0.735). Development of fat necrosis on mammography follow-up was observed in 12.8% (5/39) of the patients in the benign and in 32.1% (26/81) of the patients in the malignant group (P = 0.024). Mean follow-up time until the first sign of fat necrosis was 2.6 years in the benign group and 2.0 years in the malignant group (P = 0.187). With radiation therapy ± hormonal treatment 25 of 75 patients (33.3%) developed fat necrosis. Hormonal treatment significantly influenced the development of fat necrosis in the malignant group (odds ratio [OR]: 0.231; P = 0.029). Four of 16 patients (25.0%) having radiation and chemotherapy developed fat necrosis. Conclusion: Fat necrosis development was observed significantly more often in patients after breast cancer surgery and modern adjuvant treatment compared to benign breast surgery. However, hormonal adjuvant treatment seemed to lower the chance of fat necrosis development.

Purpose To report the impact of changing from screen-film mammography to digital mammography (DM) in a large organized national screening program. Materials and Methods A retrospective analysis of prospectively collected annual screening data from 2009-2010 to 2015-2016 for the 80 facilities of the English National Health Service Breast Cancer Screening Program, together with estimates of DM usage for three time periods, enabled the effect of DM to be measured in a study of 11.3 million screening episodes in women aged 45-70 years (mean age, 59 years). Regression models were used to estimate percentage and absolute change in detection rates due to DM. Results The overall cancer detection rate was 14% greater with DM (P < .001). There were higher rates of detection of grade 1 and 2 invasive cancers (both ductal and lobular), but no change in the detection of grade 3 invasive cancers. The recall rate was almost unchanged by the introduction of DM. At prevalent (first) screening episodes for women aged 45-52 years, DM increased the overall detection rate by 19% (P < .001) and for incident screening episodes in women aged 53-70 years by 13% (P < .001). Conclusion The overall cancer detection rate was 14% greater with digital mammography with no change in recall rates and without confounding by changes in other factors. There was a substantially higher detection of grade 1 and grade 2 invasive cancers, including both ductal and lobular cancers, but no change in the detection of grade 3 invasive cancers. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by C.I. Lee and J.M. Lee in this issue.

AIM To examine the association between recall, needle biopsy, and cancer detection rates to inform the setting of target ranges to optimise the benefit to harm ratio of breast screening programmes. MATERIALS AND METHODS Annual screening programme information from 2009/10 to 2015/16 for the 80 screening units of the English National Health Service Breast Screening Programme (totalling 11.3 million screening tests) was obtained from annual (KC62) returns. Linear regression models were used to examine the association between needle biopsy rates and recall rates and non-linear regression models to examine the association between cancer detection rates and needle biopsy rates. RESULTS The models show and quantify the diminishing returns for prevalent screens with increasing biopsy rates. A biopsy rate increase from 10 to 20 per 1,000 increases the cancer detection rate by 2.13 per 1,000 with four extra biopsies per extra cancer detected. Increasing the biopsy rate from 40 to 50 per 1,000, increases the cancer detection rate by only 0.25 per 1,000, with 40 extra biopsies per extra cancer detected. Although diminishing returns are also seen at incident screens, screening is generally more efficient. CONCLUSIONS Increasing needle biopsy rates leads to rapidly diminishing returns in cancer detection and a marked increase in non-malignant/benign needle biopsies. Much of the harms associated with screening in terms of false-positive recall rates and non-cancer biopsies occur at prevalent screens with much lower rates at incident screens. Needle biopsy rate targets should be considered together with recall rate targets to maximise benefit and minimise harm.

The purpose of the study is to test the performance of the combination of digital breast tomosynthesis (DBT) and synthetic views on the detection for cancers presenting as calcifications compared to the performance of planar mammography combined with DBT. A pilot study is presented. A set of 22 cases without cancer were collected from a Siemens Inspiration mammography system. Twenty-two simulated calcification clusters were inserted into the planar and DBT projections of 16 cases. For each case one breast and one view were used. The images were processed using Siemens proprietary software. Seven experienced mammography readers viewed the cases in three study arms: planar alone (ArmP), planar with DBT (ArmP&D) and synthetic 2D with DBT (ArmS&D). The observers marked the suspected location of the clusters and classified the likelihood of there being a suspicious calcification clusters for each case. A JAFROC figure of merit (FoM) was calculated for each study arm. The detection fractions of all cases were 46±16% (P and P&D), 34±19% (S&D). For lesion marked for recall then the maximum detection rate was 19%. The FoMs were 0.48±0.15 (P) and 0.42±0.17 (P&D), but significantly lower (p≤0.003) for S&D (0.32±0.16). This pilot study demonstrated the feasibility of undertaking a larger study. The overall detection were lower (

Purpose: To measure changes in breast density in a screening population. Method: Unprocessed mammograms were collected for 8,268 women (6034 and 2234 women with two and three sequential screening rounds respectively) with normal breasts (routine recall), from the OPTIMAM image database. The volumetric breast density (VBD), fibroglandular volume (FGV) and breast volume (BV) were determined and the changes between screening rounds calculated. Linear regression determined if the rate of change in these breast density measures varied significantly with age at initial screen. The women were split into four quartiles according to VBD in both screening rounds, and any changes in the quartile allocation of each woman determined. The VBD for these women was compared to our previously published data for women with screen detected and interval cancers. Results: Averaged over all women, the percentage change in VBD, FGV and BV, over 6 years was -11.2% (95%CI: - 12.2% to -10.2%), -5.3% (95%CI: -6.1% to -4.5%) and 11.5% (95%CI: 10.4% to 12.6%) respectively. The percentage change per month, of VBD, FGV and BD decreased significantly with age (p

Purpose To investigate the relationship between image quality measurements and the clinical performance of digital mammographic systems. Methods Mammograms containing subtle malignant non-calcification lesions and simulated malignant calcification clusters were adapted to appear as if acquired by four types of detector. Observers searched for suspicious lesions and gave these a malignancy score. Analysis was undertaken using jackknife alternative free-response receiver operating characteristics weighted figure of merit (FoM). Images of a CDMAM contrast-detail phantom were adapted to appear as if acquired using the same four detectors as the clinical images. The resultant threshold gold thicknesses were compared to the FoMs using a linear regression model and an F-test was used to find if the gradient of the relationship was significantly non-zero. Results The detectors with the best image quality measurement also had the highest FoM values. The gradient of the inverse relationship between FoMs and threshold gold thickness for the 0.25 mm diameter disk was significantly different from zero for calcification clusters (p = 0.027), but not for non-calcification lesions (p = 0.11). Systems performing just above the minimum image quality level set in the European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis resulted in reduced cancer detection rates compared to systems performing at the achievable level. Conclusions The clinical effectiveness of mammography for the task of detecting calcification clusters was found to be linked to image quality assessment using the CDMAM phantom. The European Guidelines should be reviewed as the current minimum image quality standards may be too low.

Background: The independent review of the UK National Health Service Breast Screening Programme reported (The Lancet, Volume 380, Issue 9855, Page 1778, 17 Nov 2012) on the benefits and harms of breast screening. It concluded that breast screening saves lives and acknowledged the existence of overtreatment. It encouraged randomized trials to elucidate the appropriate treatment of screen-detected DCIS to gain a better understanding of its natural history. The LORIS trial addresses the possible overtreatment of low and low/intermediate grade screen-detected (low risk) DCIS by randomizing patients to standard surgical treatment or active monitoring, each with long term follow up. Trial Design: LORIS is a phase III, multicentre, 2 arm study, with a built in 2 year Feasibility Phase, in patients confirmed to have low risk DCIS defined by strict criteria and determined by central pathology review. Patients will be randomized between standard surgery and active monitoring with annual mammography. Patients will be followed up for a minimum of 10 years. Eligibility Criteria: 1) Female, age ≥ 46 years 2) Screen-detected or incidental microcalcification (with no mass lesion clinically or on imaging) 3) Low risk DCIS on large volume vacuum-assisted biopsy, confirmed by central pathology review 4) Patient fit to undergo surgery 5) No previous breast cancer or ipsilateral DCIS diagnosis 6) Written informed consent Specific Aims: The LORIS Trial aims to establish whether patients with newly diagnosed low risk DCIS can safely avoid surgery without detriment to their wellbeing (psychological and physical) and whether those patients that do require surgery can be identified by pathological and radiological means. Primary endpoint: Ipsilateral invasive breast cancer free survival time Secondary endpoints: Overall survival; mastectomy rate; time to mastectomy; time to surgery; patient reported outcomes; health resource utilisation and assessment of predictive biomarkers. A digital image data repository and tissue bank will provide a prospective resource for both translational and imaging studies. Statistical Methods: A total of 932 patients will be randomized to a non-inferiority design to test the null hypothesis that active monitoring of women diagnosed with low risk DCIS is not non-inferior in terms of ipsilateral invasive breast cancer free survival (iiBCFS) time compared to treatment with surgery. The iiBCFS time will be compared across the two arms on a per protocol and intent-to-treat basis, using a 1-sided (α=0.05) log-rank test for non-inferiority. The iiBCFS rate is assumed to be 97.5% in the surgery arm at 5 years, utilizing 80% power to exclude a difference of more than 2.5% in the active monitoring arm. Present Accrual and Target Accrual: 32 UK centres are open for the Feasibility Phase of the trial which is nearing completion. The web-based central pathology review process is functioning efficiently, with a one week maximum turn around. Registrations and sites randomizing patients are on or above target. Randomizations are currently approximately 70% of target. A total of 60 centres will open in the main trial. Contact Information: For further information, please email the LORIS Trial Office LORIS@trials.bham.ac.uk. Citation Format: Francis A, Bartlett J, Billingham L, Bowden S, Brookes C, Dodwell D, Evans A, Fairbrother P, Fallowfield L, Gaunt C, Hanby A, Jenkins V, Matthews L, Pinder S, Pirrie S, Rea D, Reed M, Roberts T, Thomas J, Wallis M, Wilcox M, Young J. The UK LORIS trial: Randomizing patients with low or low intermediate grade ductal carcinoma in situ (DCIS) to surgery or active monitoring [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-03-01.

Optoacoustic imaging with ultrasound (OPUS) can assess in-vivo perfusion/oxygenation through surrogate measures of oxy, deoxy and total hemoglobin content in tissues. The primary aim of our study was to evaluate the ability of OPUS to detect physiological changes in the breast during the menstrual cycle and to determine qualitative/quantitative metrics of normal parenchymal tissue in pre-/post-menopausal women. The secondary aim was to assess the technique's repeatability. We performed a prospective ethically approved study in volunteers using OPUS (700, 800 and 850 nm wavelengths) in the proliferative/follicular and secretory phase of the menstrual cycle. Regions of interest (ROIs) were drawn on the most superficial region of fibroglandular tissue and same-day intra-observer repeatability was assessed. We used t-tests to interrogate differences in the OPUS measurements due to hormonal changes and interclass correlation coefficients/Bland-Altman plots to evaluate the repeatability of mean ROI signal intensities. 22 pre-menopausal and 8 post-menopausal volunteers were recruited. 21 participants underwent repeatability examinations. OPUS intensity values were significantly higher (p 0.0001) at all excitation wavelengths in the secretory compared to the proliferative/follicular phase. Post-menopausal volunteers showed similar optoacoustic values to the proliferative/follicular phase of pre-menopausal volunteers. The repeatability of the technique was comparable to other handheld ultrasound modalities. OPUS detects changes in perfusion/vascularity related to the menstrual cycle and menopausal status of breast parenchyma.ZIEL: Optoakustische Bildgebung mittels Ultraschall (OPUS) erlaubt die in-vivo Beurteilung von Perfusion/Oxygenierung mittels Surrogatmessungen von Oxy-, Deoxy- und totalem Hämoglobingehalt im Gewebe. Das vorrangige Ziel dieser Studie war es zu evaluieren, ob physiologische Veränderungen im Brustparenchym während des Menstruationszyklus nachweisbar sind und qualitative sowie quantitative Merkmale normalen Brustparenchyms in prä- und postmenopausalen Probandinnen zu bestimmen. Als weiteres Ziel wurde die Reproduzierbarkeit dieser Technik evaluiert. Die vorliegende prospektive Studie zur Evaluierung von OPUS (700, 800 und 850 nm Wellenlänge) an freiwilligen Probandinnen während der proliferativen/follikulären und sekretorischen Zyklusphasen wurde von der lokalen Ethikkommission positive beurteilt. Regions of interest (ROIs) wurden im oberflächlichsten fibroglandulären Gewebe gezeichnet und die Intraobserver-Reproduzierbarkeit wurde am selben Untersuchungstag beurteilt. Um Unterschiede zwischen OPUS-Messungen in Abhängigkeit von Zyklusphasen zu beurteilen, wurden t-Tests verwendet. Interklassen-Korrelationskoeffizienten/Bland-Altman Plots wurden verwendet um die Reproduzierbarkeit der mittleren ROI Signalintensität zu untersuchen. 22 prämenopausale und 8 postmenopausale Probandinnen wurden rekrutiert. 21 Probandinnen unterzogen sich Reproduzierbarkeitstests. Unabhängig von der Exzitationswellenlänge waren OPUS Intensitätswerte während der sekretorischen Phase signifikant höher (p 0,0001) als während der proliferativen/follikulären Phase. Die Messwerte in postmenopausalen Probandinnen glichen denen prämenopausaler Probandinnen während der proliferativen/follikulären Phase. Die Reproduzierbarkeit dieser Technik glich der anderer Ultraschallhandgeräte. OPUS detektiert Veränderungen der Perfusion/Vaskularisation des Brustparenchyms in Abhängigkeit von Menstruationszyklus und Menopausenstatus.

Purpose To investigate the effect of double readings by a second radiologist on recall rates, cancer detection, and characteristics of cancers detected in the National Health Service Breast Screening Program in England. Materials and Methods In this retrospective analysis, 805 206 women were evaluated through screening and diagnostic test results by extracting 1 year of routine data from 33 English breast screening centers. Centers used double reading of digital mammograms, with arbitration if there were discrepant interpretations. Information on reader decisions, with results of follow-up tests, were used to explore the effect of the second reader. The statistical tests used were the test for equality of proportions, the χ2 test for independence, and the t test. Results The first reader recalled 4.76% of women (38 295 of 805 206 women; 95% confidence interval [CI]: 4.71%, 4.80%). Two readers recalled 6.19% of women in total (49 857 of 805 206 women; 95% CI: 6.14%, 6.24%), but arbitration of discordant readings reduced the recall rate to 4.08% (32 863 of 805 206 women; 95% CI: 4.04%, 4.12%; P < .001). A total of 7055 cancers were detected, of which 627 (8.89%; 95% CI: 8.22%, 9.55%; P < .001) were detected by the second reader only. These additional cancers were more likely to be ductal carcinoma in situ (30.5% [183 of 600] vs 22.0% [1344 of 6114]; P < .001), and additional invasive cancers were smaller (mean size, 14.2 vs 16.7 mm; P < .001), had fewer involved nodes, and were likely to be lower grade. Conclusion Double reading with arbitration reduces recall and increases cancer detection compared with single reading. Cancers detected only by the second reader were smaller, of lower grade, and had less nodal involvement. © RSNA, 2018.

The use of conventional clinical trials to optimise technology and techniques in breast cancer screening carries with it issues of dose, high cost and delay. This has motivated the development of Virtual Clinical Trials (VCTs) as an alternative in-silico assessment paradigm. However, such an approach requires a set of modelling tools that can realistically represent the key biological and technical components within the imaging chain. The OPTIMAM image simulation toolbox provides a complete validated end-to-end solution for VCTs, wherein commonly-found regular and irregular lesions can be successfully and realistically simulated. As spiculated lesions are the second most common form of solid mass we report on our latest developments to produce realistic spiculated lesion models, with particular application in Alternative Forced Choice trials. We make use of sets of spicules drawn using manually annotated landmarks and interpolated by a fitted 3D spline for each spicule. Once combined with a solid core, these are inserted into 2D and tomosynthesis image segments and blended using a combination of elongation, rotational alignment with background, spicule twisting and core radial contraction effects. A mixture of real and simulated images (86 2D and 86 DBT images) with spiculated lesions were presented to an experienced radiologist in an observer study. The latest observer study results demonstrated that 88.4% of simulated images of lesions in 2D and 67.4% of simulated lesions in DBT were rated as definitely or probably real on a six-point scale. This presents a significant improvement on our previous work which did not employ any background blending algorithms to simulate spiculated lesions in clinical images.

Reviewing interval cancers and prior screening mammograms are a key measure to monitor screening performance. Radiological analysis of the imaging features in prior mammograms and retrospective classification are an important educational tool for readers to improve individual performance. The requirements of remote, collaborative image review sessions, such as those required to run a remote interval cancer review, are variable and demand a flexible and configurable software solution that is not currently available on commercial workstations. The wide range of requirements for both collection and remote review of interval cancers has precipitated the creation of extensible medical image viewers and accompanying systems. In order to allow remote viewing, an application has been designed to allow workstation-independent, PACS-less viewing and interaction with medical images in a remote, collaborative manner, providing centralised reporting and web-based feedback. A semi-automated process, which allows the centralisation of interval cancer cases, has been developed. This stand-alone, flexible image collection toolkit provides the extremely important function of bespoke, ad-hoc image collection at sites where there is no dedicated hardware. Web interfaces have been created which allow a national or regional administrator to organise, coordinate and administer interval cancer review sessions and deploy invites to session members to participate. The same interface allows feedback to be analysed and distributed. The eICR provides a uniform process for classifying interval cancers across the NHSBSP, which facilitates rapid access to a robust 'external' review for patients and their relatives seeking answers about why their cancer was 'missed'.

Overdiagnosis is the inevitable flip side of early detection resulting in unnecessary labelling of well women with a diagnosis of cancer and possible unnecessary treatment. Overdiagnosis occurs because breast cancers have different rates of growth and slow-growing cancers are preferentially detected by screening. Some of these slow-growing screen-detected cancers may never have been clinically apparent during an individual's lifetime. Evaluating the benefits and risks of screening are complex, but this has been performed for the UK population by an independent review led by Professor Marmot. It might be possible to limit overdiagnosis by identifying women with "low-risk disease" earlier, either at the point of screening when additional investigations could be delayed (possibly for ever) so that they are not subjected to additional diagnostic tests, or at the point of diagnosis. Both these options would require major re-education of clinicians and the public who would need to accept that screening is "deliberately ignoring a cancer". There is a long surgical history of reducing the burden of treatment, which continues today with trials of management of the axilla and reducing or even omitting radiotherapy for low-risk disease. The Low Risk Ductal Carcinoma In Situ trial (LORIS) has started to identify a group of breast cancer patients who could avoid surgery and be offered active monitoring. We need to consider planning a similar trial for low-risk invasive breast cancer.