Implementing Multifactorial Risk Assessment with Polygenic Risk Scores for Personalized Breast Cancer Screening in the Population Setting: Challenges and Opportunities.

Risk-stratified breast screening has been proposed as a strategy to overcome the limitations of age-based screening. A prospective cohort study was undertaken within the PERSPECTIVE I&I project, which will generate the first Canadian evidence on multifactorial breast cancer risk assessment in the population setting to inform the implementation of risk-stratified screening. Recruited females aged 40-69 unaffected by breast cancer, with a previous mammogram, underwent multifactorial breast cancer risk assessment. The adoption of multifactorial risk assessment, the effectiveness of methods for collecting risk factor information and the costs of risk assessment were examined. Associations between participant characteristics and study sites, as well as data collection methods, were assessed using logistic regression; all p-values are two-sided. Of the 4246 participants recruited, 88.4% completed a risk assessment, with 79.8%, 15.7% and 4.4% estimated at average, higher than average and high risk, respectively. The total per-participant cost for risk assessment was CAD 315. Participants who chose to provide risk factor information on paper/telephone (27.2%) vs. online were more likely to be older (p = 0.021), not born in Canada (p = 0.043), visible minorities (p = 0.01) and have a lower attained education (p < 0.0001) and perceived fair/poor health (p < 0.001). The 34.4% of participants requiring risk factor verification for missing/unusual values were more likely to be visible minorities (p = 0.009) and have a lower attained education (p ≤ 0.006). This study demonstrates the feasibility of risk assessment for risk-stratified screening at the population level. Implementation should incorporate an equity lens to ensure cancer-screening disparities are not widened.

Diagnostic accuracy of supplemental three-dimensional breast ultrasound in the work-up of BI-RADS 0 screening recalls.

OBJECTIVE: To evaluate the diagnostic accuracy of supplemental 3D automated breast ultrasound (ABUS) in the diagnostic work-up of BI-RADS 0 recalls. We hypothesized that 3D ABUS may reduce the benign biopsy rate. MATERIALS AND METHODS: In this prospective multicenter diagnostic study, screening participants recalled after a BI-RADS 0 result underwent bilateral 3D ABUS supplemental to usual care: digital breast tomosynthesis (DBT) and targeted hand-held ultrasound (HHUS). Sensitivity, specificity, positive predictive value, and negative predictive value of 3D ABUS, and DBT plus HHUS, were calculated. New 3D ABUS findings and changes of management (biopsy or additional imaging) were recorded. RESULTS: A total of 501 women (median age 55 years, IQR [51-64]) with 525 BI-RADS 0 lesions were included between April 2018 and March 2020. Cancer was diagnosed in 45 patients. 3D ABUS sensitivity was 72.1% (95% CI [57.2-83.4%]), specificity 84.4% (95% CI [80.8-87.4%]), PPV 29.2% (95% CI [21.4-38.5%]), and NPV 97.1% 95.0-98.4%). Sensitivity of DBT plus HHUS was 100% (95% CI [90.2-100%]), specificity 71.4% (95% CI [67.2-75.2%]), PPV 23.8% (95% CI [18.1-30.5%]) and NPV 100% (95% CI [98.7-100%]). Twelve out of 43 (27.9%) malignancies in BI-RADS 0 lesions were missed on 3D ABUS, despite being detected on DBT and/or HHUS. Supplemental 3D ABUS resulted in the detection of 57 new lesions and six extra biopsy procedures, all were benign. CONCLUSION: 3D ABUS in the diagnostic work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with HHUS and/or DBT and should not be used to omit biopsy. Supplemental 3D ABUS increases the benign biopsy rate. TRIAL REGISTRATION: Dutch Trial Register, available via https://www.onderzoekmetmensen.nl/en/trial/29659 CRITICAL RELEVANCE STATEMENT: Supplemental 3D automated breast ultrasound in the work-up of BI-RADS 0 recalls may miss over a quarter of cancers detected with other methods and should not be used to omit biopsy; ABUS findings did increase benign biopsy rate. KEY POINTS: Automated breast ultrasound (ABUS) may miss over 25% of cancers detectable by alternative methods. Don't rely solely on 3D ABUS to assess indication for biopsy. New findings with supplemental 3D ABUS increase the benign biopsy rate.

The Public's Intended Uptake of Hypothetical Esophageal Adenocarcinoma Screening Scenarios: A Nationwide Survey.

INTRODUCTION: Screening for early esophageal adenocarcinoma (EAC) may potentially reduce EAC-related mortality and morbidity. This study aimed to examine the Dutch population's intended uptake of 3 hypothetical EAC screening test scenarios and preferences for potential future organization. METHODS: A total of 8,350 Dutch individuals aged 45-75 years were invited, of whom 2,258 completed a web-based survey. Participants were randomly assigned to 1 of 3 hypothetical screening test scenarios (i.e., transnasal endoscopy, ingestible cell collection device, or breath analysis). The primary outcome was intended uptake. Secondary outcomes included acceptance of screening eligibility criteria and preferences regarding invitation, counseling, and diagnostic follow-up. We performed exploratory univariable and multivariable regression analyses to assess which determinants were associated with EAC screening intent. RESULTS: Intended uptake of screening was highest in the breath analysis scenario (95%), followed by conventional upper endoscopy (78%), an ingestible cell collection device (75%), and transnasal endoscopy (68%) ( P < 0.001). Anticipating discomfort was most strongly associated with decreased intention to undergo transnasal endoscopy (odds ratio 0.18, 95% confidence interval 0.11-0.29) or swallow a cell collection device (odds ratio 0.20, 95% confidence interval 0.13-0.32). Cancer worry and high acceptance of test sensitivity/specificity were consistently associated with a positive intention to participate in screening. Inviting persons for screening based on gastroesophageal reflux disease symptoms, age, or the output of a risk prediction model was acceptable to 74%, 69%, and 66%, respectively. Inviting only men was acceptable for only 41% of women. The majority (58%) preferred to be invited by a public health organization, and 32% of the participants preferred to discuss their decision to participate with a healthcare professional. DISCUSSION: Participants in this study self-selected through a web-based survey, potentially introducing selection bias. Participants generally intended to participate in EAC screening, although the level of intent depended on the discomfort and performance associated with the offered screening test. Determining eligibility based on gastroesophageal reflux disease symptoms, age, or a risk calculator, but not sex, would be acceptable to most individuals.

Oesophageal cancer awareness and anticipated time to help-seeking: results from a population-based survey.

BACKGROUND: Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking. METHODS: We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month). RESULTS: The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87). CONCLUSION: Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes.

Women's Experiences with Digital Breast Tomosynthesis and Targeted Breast Ultrasound for Focal Breast Complaints: A Survey Study.

Background: Owing to its high sensitivity, as concluded in the Breast UltraSound Trial (BUST), targeted ultrasound (US) now seems a promising accurate stand-alone modality for diagnostic evaluation of breast complaints. This approach implies omission of bilateral digital breast tomosynthesis (DBT) in women with clearly benign US findings. Within BUST, radiologists started with US followed by DBT. This side-study investigates women's experiences with DBT, their main motivation to undergo diagnostic imaging, and their view on US as a stand-alone modality. Methods: A subset of BUST participants completed a questionnaire on their DBT experiences, reason for undergoing diagnostic assessment, and view on US-only diagnostics. Responses were analyzed with descriptive statistics and logistic regression analyses. Results: In total, 778 of 838 women (response rate 92.8%) were included (M = 47, SD = 11.16). Of them, 16.8% reported no burden of DBT, 33.5% slight burden, 31.0% moderate, and 12.7% severe burden. Furthermore, 13% reported no pain, 35.3% slight pain, 33.2% moderate, and 11.3% severe pain. Moreover, 88.3% indicated that the most important reason for breast assessment was explanation of their complaint and to rule out breast cancer, whereas 3.2% wanted to "check" both breasts. And 82.4% reported satisfaction with US only in case of a nonmalignancy. Conclusions: Our study shows that most women in the diagnostic setting experience at least slight-to-moderate DBT-related burden and pain, and that explanation for their symptoms is their main interest. Also, the majority report satisfaction with US only in case of nonmalignant findings. However, exploration of women's perspectives outside this study is needed as our participants all underwent both examinations.

The prognostic potential of mammographic growth rate of invasive breast cancer in the Nijmegen breast cancer screening cohort.

OBJECTIVES: Insight into the aggressiveness of potential breast cancers found in screening may optimize recall decisions. Specific growth rate (SGR), measured on mammograms, may provide valuable prognostic information. This study addresses the association of SGR with prognostic factors and overall survival in patients with invasive carcinoma of no special type (NST) from a screened population. METHODS: In this historic cohort study, 293 women with NST were identified from all participants in the Nijmegen screening program (2003-2007). Information on clinicopathological factors was retrieved from patient files and follow-up on vital status through municipalities. On consecutive mammograms, tumor volumes were estimated. After comparing five growth functions, SGR was calculated using the best-fitting function. Regression and multivariable survival analyses described associations between SGR and prognostic factors as well as overall survival. RESULTS: Each one standard deviation increase in SGR was associated with an increase in the Nottingham prognostic index by 0.34 [95% confidence interval (CI): 0.21-0.46]. Each one standard deviation increase in SGR increased the odds of a tumor with an unfavorable subtype (based on histologic grade and hormone receptors; odds ratio 2.14 [95% CI: 1.45-3.15]) and increased the odds of diagnosis as an interval cancer (versus screen-detected; odds ratio 1.57 [95% CI: 1.20-2.06]). After a median of 12.4 years of follow-up, 78 deaths occurred. SGR was not associated with overall survival (hazard ratio 1.12 [95% CI: 0.87-1.43]). CONCLUSIONS: SGR may indicate prognostically relevant differences in tumor aggressiveness if serial mammograms are available. A potential association with cause-specific survival could not be determined and is of interest for future research.

Deep learning-based breast region segmentation in raw and processed digital mammograms: generalization across views and vendors.

Purpose: We developed a segmentation method suited for both raw (for processing) and processed (for presentation) digital mammograms (DMs) that is designed to generalize across images acquired with systems from different vendors and across the two standard screening views. Approach: A U-Net was trained to segment mammograms into background, breast, and pectoral muscle. Eight different datasets, including two previously published public sets and six sets of DMs from as many different vendors, were used, totaling 322 screen film mammograms (SFMs) and 4251 DMs (2821 raw/processed pairs and 1430 only processed) from 1077 different women. Three experiments were done: first training on all SFM and processed images, second also including all raw images in training, and finally testing vendor generalization by leaving one dataset out at a time. Results: The model trained on SFM and processed mammograms achieved a good overall performance regardless of projection and vendor, with a mean (±std. dev.) dice score of 0.96±0.06 for all datasets combined. When raw images were included in training, the mean (±std. dev.) dice score for the raw images was 0.95±0.05 and for the processed images was 0.96±0.04. Testing on a dataset with processed DMs from a vendor that was excluded from training resulted in a difference in mean dice varying between -0.23 to +0.02 from that of the fully trained model. Conclusions: The proposed segmentation method yields accurate overall segmentation results for both raw and processed mammograms independent of view and vendor. The code and model weights are made available.

Method of primary breast cancer detection and the disease-free interval, adjusting for lead time.

BACKGROUND: Little is known about the impact of screen-detected breast cancer compared with clinically detected breast cancer on the disease-free interval (ie, free from locoregional recurrences, distant metastasis, contralateral breast cancer). Moreover, it is thought that most studies overestimate the beneficial effect of screening, as they do not adjust for lead time. We investigated the association between method of breast cancer detection and disease-free interval, taking lead time into account. METHODS: Women aged 50-76 years, diagnosed with breast cancer between 2005 and 2008 were selected from the Netherlands Cancer Registry. Women diagnosed in 2005 were divided into screen-detected and clinically detected cancer and had a follow-up of 10 years (2005 cohort). Women diagnosed in 2006-2008 were divided into screen-detected, interval, and nonscreen-related cancer and had a follow-up of 5 years (2006-2008 cohort). A previously published method was used to adjust for lead time. Analyses were repeated correcting for confounding variables instead of lead time. RESULTS: The 2005 cohort included 6215 women. Women with screen-detected cancer had an improved disease-free interval compared with women with clinically detected cancer (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.68 to 0.87). The 2006-2008 cohort included 15 176 women. Women with screen-detected or interval cancer had an improved disease-free interval compared with women with nonscreen-related cancer (HR = 0.76, 95% CI = 0.66 to 0.88; HR = 0.88, 95% CI = 0.78 to 0.99, respectively). Correcting for confounders instead of lead time did not change associations. CONCLUSION: Women with screen-detected cancer had an improved disease-free interval compared with women with a nonscreen-related or clinically detected cancer, after correction for lead time.

Long-term cause of death patterns and mode of breast cancer detection in The Netherlands, 2004-2019.

OBJECTIVE: Early detection through mammographic screening and various treatment modalities of cancer may have changed life expectancy and cause-specific mortality of breast cancer patients. We aimed to determine the long-term cause of death patterns in screening-detected patients and clinically diagnosed patients in the Netherlands compared with the general population. METHODS: Using data from the Netherlands Cancer Registry and Statistics Netherlands of around 26,000 women, aged 50-75 at diagnosis and surgically treated for invasive breast cancer in 2004-2008, we compared patients with screening-detected and clinically diagnosed cancer for major causes of death until 2020. The expected number of all-cause and cause-specific deaths was calculated using rates of the general population. RESULTS: During the follow-up period, 4310 women died. The age-standardised all-cause mortality ratio for the screening-detected cancer group was 1.41 (95% confidence interval (95% CI), 1.37-1.46). A higher mortality ratio was observed for patients with clinically detected cancer: 2.27 (95% CI, 2.19-2.34). The observed versus expected breast cancer mortality ratio in the screening-detected patient group was 8.92 (95% CI, 8.45-9.40) and 20.23 (19.38-21.09) in the clinical group. Excess mortality was found for lung cancer in both patient groups, and small elevations for circulatory and respiratory disease in the clinically detected group. CONCLUSION: Our results indicate that for the screening group no other causes of death but breast and lung cancer were prominent compared with the general population. The clinical group showed excess mortality for some other causes of death as well, suggesting a less healthy group compared with the general population.

Dutch, UK and US professionals' perceptions of screening for Barrett's esophagus and esophageal adenocarcinoma: a concept mapping study.

BACKGROUND: Novel, less-invasive technologies to screen for Barrett's esophagus (BE) may enable a paradigm shift in early detection strategies for esophageal adenocarcinoma (EAC). Understanding professionals' perspectives on screening is important to determine how to proceed. We aimed to explore and compare professionals' perceptions of screening for BE and EAC screening in three countries. METHODS: In this study, 29 Dutch, 20 British and 18 American health care professionals (clinicians, researchers and policy makers) participated in concept mapping: a mixed-methods consensus building methodology. Statements on perceived barriers, facilitators, advantages, disadvantages, implications or worries associated with screening for BE and EAC were collected in asynchronous digital brainstorm sessions. Subsequently, participants sorted the statements into groups according to thematic similarity and assessed the relevance of each statement in evaluating the acceptability of BE and EAC screening. Multidimensional scaling and cluster analysis were used to map the associations between generated statements. RESULTS: Professionals across three countries identified eight consistent themes that relate to their perceptions of screening for BE and EAC: (1) Benefits, (2) Harms, (3) Clinical effectiveness concerns, (4) Screening population, (5) Screening modality, (6) Resources, (7) Ownership, and (8) Public communication. Dutch and American professionals prioritized the potential health benefits of screening but also questioned clinical impact. In contrast, British participants prioritized identification of the screening population and suitable test. CONCLUSIONS: Most professionals see potential in less-invasive screening tests for BE and EAC but underline the need to define the target screening population and determine benefits and harms before widely employing them. Successful implementation will require thoughtful consideration of the involvement of general practitioners, readiness of endoscopy and pathology services, balanced public communication, and country-specific regulations.

Optimizing the Pairs of Radiologists That Double Read Screening Mammograms.

Background Despite variation in performance characteristics among radiologists, the pairing of radiologists for the double reading of screening mammograms is performed randomly. It is unknown how to optimize pairing to improve screening performance. Purpose To investigate whether radiologist performance characteristics can be used to determine the optimal set of pairs of radiologists to double read screening mammograms for improved accuracy. Materials and Methods This retrospective study was performed with reading outcomes from breast cancer screening programs in Sweden (2008-2015), England (2012-2014), and Norway (2004-2018). Cancer detection rates (CDRs) and abnormal interpretation rates (AIRs) were calculated, with AIR defined as either reader flagging an examination as abnormal. Individual readers were divided into performance categories based on their high and low CDR and AIR. The performance of individuals determined the classification of pairs. Random pair performance, for which any type of pair was equally represented, was compared with the performance of specific pairing strategies, which consisted of pairs of readers who were either opposite or similar in AIR and/or CDR. Results Based on a minimum number of examinations per reader and per pair, the final study sample consisted of 3 592 414 examinations (Sweden, n = 965 263; England, n = 837 048; Norway, n = 1 790 103). The overall AIRs and CDRs for all specific pairing strategies (Sweden AIR range, 45.5-56.9 per 1000 examinations and CDR range, 3.1-3.6 per 1000; England AIR range, 68.2-70.5 per 1000 and CDR range, 8.9-9.4 per 1000; Norway AIR range, 81.6-88.1 per 1000 and CDR range, 6.1-6.8 per 1000) were not significantly different from the random pairing strategy (Sweden AIR, 54.1 per 1000 examinations and CDR, 3.3 per 1000; England AIR, 69.3 per 1000 and CDR, 9.1 per 1000; Norway AIR, 84.1 per 1000 and CDR, 6.3 per 1000). Conclusion Pairing a set of readers based on different pairing strategies did not show a significant difference in screening performance when compared with random pairing. © RSNA, 2023.

Impact of the COVID-19 pandemic on breast cancer incidence and tumor stage in the Netherlands and Norway: A population-based study.

BACKGROUND: Comparing the impact of the COVID-19 pandemic on the incidence of newly diagnosed breast tumors and their tumor stage between the Netherlands and Norway will help us understand the effect of differences in governmental and social reactions towards the pandemic. METHODS: Women newly diagnosed with breast cancer in 2017-2021 were selected from the Netherlands Cancer Registry and the Cancer Registry of Norway. The crude breast cancer incidence rate (tumors per 100,000 women) during the first (March-September 2020), second (October 2020-April 2021), and Delta COVID-19 wave (May-December 2021) was compared with the incidence rate in the corresponding periods in 2017, 2018, and 2019. Incidence rates were stratified by age group, method of detection, and clinical tumor stage. RESULTS: During the first wave breast cancer incidence declined to a larger extent in the Netherlands than in Norway (27.7% vs. 17.2% decrease, respectively). In both countries, incidence decreased in women eligible for screening. In the Netherlands, incidence also decreased in women not eligible for screening. During the second wave an increase in the incidence of stage IV tumors in women aged 50-69 years was seen in the Netherlands. During the Delta wave an increase in overall incidence and incidence of stage I tumors was seen in Norway. CONCLUSION: Alterations in breast cancer incidence and tumor stage seem related to a combined effect of the suspension of the screening program, health care avoidance due to the severity of the pandemic, and other unknown factors.

Acceptability of risk-based triage in cervical cancer screening: A focus group study.

BACKGROUND: Compared to the previous cytology-based program, the introduction of primary high-risk human papillomavirus (hrHPV) based screening in 2017 has led to an increased number of referrals. To counter this, triage of hrHPV-positive women in cervical cancer screening can potentially be optimized by taking sociodemographic and lifestyle risk factors for cervical abnormalities into account. Therefore, it is essential to gain knowledge of the views of women (30-60 years) eligible for cervical cancer screening. OBJECTIVE: The main goal of this qualitative study was to gain insight in the aspects that influence acceptability of risk-based triage in cervical cancer screening. DESIGN: A focus group study in which participants were recruited via four general medical practices, and purposive sampling was used to maximize heterogeneity with regards to age, education level, and cervical cancer screening experiences. APPROACH: The focus group discussions were transcribed verbatim and analyzed using reflexive thematic analysis. PARTICIPANTS: A total of 28 women (average age: 45.2 years) eligible for cervical cancer screening in The Netherlands participated in seven online focus group discussions. Half of the participants was higher educated, and the participants differed in previous cervical cancer screening participation and screening result. KEY RESULTS: In total, 5 main themes and 17 subthemes were identified that determine the acceptability of risk-stratified triage. The main themes are: 1) adequacy of the screening program: an evidence-based program that is able to minimize cancer incidence and reduce unnecessary referrals; 2) personal information (e.g., sensitive topics and stigma); 3) emotional impact: fear and reassurance; 4) communication (e.g., transparency); and 5) autonomy (e.g., prevention). CONCLUSION: The current study highlights several challenges regarding the development and implementation of risk-based triage that need attention in order to be accepted by the target group. These challenges include dealing with sensitive topics and a transparent communication strategy.

The effect of a pre-scheduled appointment on attendance in a population-based mammography screening programme.

BACKGROUND: Pre-scheduled appointments can increase attendance in breast cancer screening programmes compared to 'open invitations' but relatively few randomized controlled trials exist. We investigated the effect of a pre-scheduled appointment on uptake in the Flemish population-based mammography screening programme. METHODS: Between September and December 2022, a total of 4798 women were randomly assigned to receive either a pre-scheduled appointment or open invitation. The difference in attendance was compared with Poisson regression analysis for the primary endpoint (attendance ≤92 days after date of invitation), yielding relative risks (RRs). This was done separately for three groups: women invited to a mobile unit and a history of nonattendance (group M-NA); women invited to a hospital-based unit and a history of nonattendance (group HB-NA); women invited to a hospital-based unit and a history of irregular attendance (group HB-IA). There were no women invited to a mobile unit and a history of irregular attendance. RESULTS: The RRs in favour of the pre-scheduled appointment were 2.3 [95% confidence interval (CI) 1.80-2.88], 1.8 (95% CI 1.07-2.97) and 1.8 (95% CI 1.43-2.39), for groups M-NA, HB-NA and HB-IA, respectively. We found no statistically significant difference between the various RRs. The respective absolute gains in attendance between pre-scheduled appointment and open invitation were 8.3%, 4.4% and 15.8%. CONCLUSIONS: Sending an invitation with a pre-scheduled appointment is an effective tool to increase screening attendance in both mobile and hospital-based screening units. The pre-scheduled appointment is associated with a considerable absolute gain in attendance which varies depending on the screening history.

Lesion detection in digital breast tomosynthesis: human reader experiments indicate no benefit from the integration of information from multiple planes.

Purpose: In digital breast tomosynthesis (DBT), radiologists need to review a stack of 20 to 80 tomosynthesis images, depending upon breast size. This causes a significant increase in reading time. However, it is currently unknown whether there is a perceptual benefit to viewing a mass in the 3D tomosynthesis volume. To answer this question, this study investigated whether adjacent lesion-containing planes provide additional information that aids lesion detection for DBT-like and breast CT-like (bCT) images. Method: Human reader detection performance was determined for low-contrast targets shown in a single tomosynthesis image at the center of the target (2D) or shown in the entire tomosynthesis image stack (3D). Using simulations, targets embedded in simulated breast backgrounds, and images were generated using a DBT-like (50 deg angular range) and a bCT-like (180 deg angular range) imaging geometry. Experiments were conducted with spherical and capsule-shaped targets. Eleven readers reviewed 1600 images in two-alternative forced-choice experiments. The area under the receiver operating characteristic curve (AUC) and reading time were computed for the 2D and 3D reading modes for the DBT and bCT imaging geometries and for both target shapes. Results: Spherical lesion detection was higher in 2D mode than in 3D, for both DBT- and bCT-like images (DBT: AUC2D=0.790, AUC3D=0.735, P=0.03; bCT: AUC2D=0.869, AUC3D=0.716, P<0.05), but equivalent for capsule-shaped signals (DBT: AUC2D=0.891, AUC3D=0.915, P=0.19; bCT: AUC2D=0.854, AUC3D=0.847, P=0.88). Average reading time was up to 134% higher for 3D viewing (P<0.05). Conclusions: For the detection of low-contrast lesions, there is no inherent visual perception benefit to reviewing the entire DBT or bCT stack. The findings of this study could have implications for the development of 2D synthetic mammograms: a single synthesized 2D image designed to include all lesions present in the volume might allow readers to maintain detection performance at a significantly reduced reading time.

Professionals' views on the justification for esophageal adenocarcinoma screening: A systematic literature search and qualitative analysis.

Screening for early esophageal adenocarcinoma (EAC), including screening for its precursor Barrett's esophagus (BE), has the potential to reduce EAC-related mortality and morbidity. This literature review aimed to explore professionals' views on the justification for EAC screening. A systematic search of Ovid Medline, EMBASE, and PsycInfo, from January 1, 2000 to September 22, 2022, identified 5 original studies and 63 expert opinion articles reporting professionals' perspectives on EAC screening. Included articles were qualitatively analyzed using the framework method, which was deductively led by modernized screening principles. The analyses showed that many professionals are optimistic about technological advancements in BE detection and treatment. However, views on whether the societal burden of EAC merits screening were contradictory. In addition, knowledge of the long-term benefits and risks of EAC screening is still considered insufficient. There is no consensus on who to screen, how often to screen, which screening test to use, and how to manage non-dysplastic BE. Professionals further point out the need to develop technology that facilitates automated test sample processing and public education strategies that avoid causing disproportionately high cancer worry and social stigma. In conclusion, modernized screening principles are currently insufficiently fulfilled to justify widespread screening for EAC. Results from future clinical screening trials and risk prediction modeling studies may shift professionals' thoughts regarding justification for EAC screening.

The dilemma of recalling well-circumscribed masses in a screening population: A narrative literature review and exploration of Dutch screening practice.

BACKGROUND: In Dutch breast cancer screening, solitary, new or growing well-circumscribed masses should be recalled for further assessment. This results in cancers detected but also in false positive recalls, especially at initial screening. The aim of this study was to determine characteristics of well-circumscribed masses at mammography and identify potential methods to improve the recall strategy. METHODS: A systematic literature search was performed using PubMed. In addition, follow-up data were retrieved on all 8860 recalled women in a Dutch screening region from 2014 to 2019. RESULTS: Based on 15 articles identified in the literature search, we found that probably benign well-circumscribed masses that were kept under surveillance had a positive predictive value (PPV) of 0-2%. New or enlarging solitary well-circumscribed masses had a PPV of 10-12%. In general the detected carcinomas had a favorable prognosis. In our exploration of screening practice, 25% of recalls (2133/8860) were triggered by a well-circumscribed mass. Those recalls had a PPV of 2.0% for initial and 10.6% for subsequent screening. Most detected carcinomas had a favorable prognosis as well. CONCLUSION: To recognize malignancies presenting as well-circumscribed masses, identifying solitary, new or growing lesions is key. This information is missing at initial screening since prior examinations are not available, leading to a low PPV. Access to prior clinical examinations may therefore improve this PPV. In addition, given the generally favorable prognosis of screen-detected malignant well-circumscribed masses, one may opt to recall these lesions at subsequent screening, if grown, rather than at initial screening.

Cumulative risks of false positive recall and screen-detected breast cancer after multiple screening examinations.

Women tend to make a decision about participation in breast cancer screening and adhere to this for future invitations. Therefore, our study aimed to provide high-quality information on cumulative risks of false-positive (FP) recall and screen-detected breast cancer over multiple screening examinations. Individual Dutch screening registry data (2005-2018) were gathered on subsequent screening examinations of 92 902 women age 49 to 51 years in 2005. Survival analyses were used to calculate cumulative risks of a FP and a true-positive (TP) result after seven examinations. Data from 66 472 women age 58 to 59 years were used to extrapolate to 11 examinations. Participation, detection and additional FP rates were calculated for women who previously received FP results compared to women with true negative (TN) results. After 7 examinations, the cumulative risk of a TP result was 3.7% and the cumulative risk of a FP result was 9.1%. After 11 examinations, this increased to 7.1% and 13.5%, respectively. Following a FP result, participation was lower (71%-81%) than following a TN result (>90%). In women with a FP result, more TP results (factor 1.59 [95% CI: 1.44-1.72]), more interval cancers (factor 1.66 [95% CI: 1.41-1.91]) and more FP results (factor 1.96 [95% CI: 1.87-2.05]) were found than in women with TN results. In conclusion, due to a low recall rate in the Netherlands, the cumulative risk of a FP recall is relatively low, while the cumulative risk of a TP result is comparable. Breast cancer diagnoses and FP results were more common in women with FP results than in women with TN results, while participation was lower.

US and Digital Breast Tomosynthesis in Women with Focal Breast Complaints: Results of the Breast US Trial (BUST).

Background Digital breast tomosynthesis (DBT) followed by targeted US is commonly performed to evaluate women with localized breast complaints. However, the added value of DBT in addition to targeted US is unknown. Omitting DBT may be cost-effective and improve patient comfort but may miss potential breast cancer. Purpose To assess whether an imaging protocol consisting of targeted US alone may be feasible for the diagnostic work-up of women with localized symptoms and to assess the supplemental value of DBT in this reversed setting. Materials and Methods This prospective study enrolled consecutive women aged 30 years or older with focal breast complaints in three hospitals in the Netherlands between September 2017 and June 2019. In all participants, first, targeted US was evaluated, and if needed, biopsy was performed, followed by DBT. The primary outcome was the frequency of breast cancer detected with DBT when US was negative. Secondary outcomes were frequency of cancer detected with DBT elsewhere in the breast and combined overall sensitivity of US plus DBT. The reference standard was 1 year follow-up or histopathologic examination. Results There were 1961 women (mean age ± SD, 47 years ± 12) enrolled. Based on initial US alone, 1587 participants (81%) had normal or benign findings and 1759 (90%) had a definitive accurate diagnosis. In total, 204 breast cancers were detected during initial work-up. The frequency of malignancy was 10% (192 of 1961 participants) with US (US sensitivity, 98.5% [95% CI: 96, 100]; US specificity, 90.8% [95% CI: 89, 92]). DBT depicted three unobserved malignant lesions at the complaint site and 0.41% (eight of 1961 participants) of incidental malignant findings in participants without symptomatic cancer. Conclusion Compared with combined US and DBT, US was accurate as a stand-alone breast imaging modality in the assessment of focal breast complaints. The rate of cancer detection of cancers elsewhere in the breast with DBT is comparable to cancer detection rate of screening mammography. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Newell in this issue.

Expanding the boundaries of previously obtained informed consent in research: Views from participants in the Personalised Risk-based Mammascreening study.

INTRODUCTION: Understanding participants' concerns and information needs regarding broadened consent is crucial to ensure transparency and participant autonomy. Our study qualitatively examined these issues in women participating in the Personalized RISk-based MAmmascreening study (PRISMA). The original PRISMA informed consent was project-specific (i.e., breast cancer research), limiting the scope of secondary research. We explored participants' needs for broadened consent to preserve informed decision-making while maximising the potential re-use of data. METHODS: Focus groups (FGs) were performed following a semistructured discussion guide. Two independent researchers analysed the data thematically using an inductive approach. FINDINGS: Twenty-three asymptomatic women and 13 women diagnosed with breast cancer were randomly divided into six FGs. Four superordinate themes were identified: (1) Normalization, (2) Attitude towards the pharmaceutical industry, (3) Privacy and (4) Knowledge. Our participants viewed data sharing as an important conduit for advancing medical science. Perceived integrity was more often attributed to noncommercial than commercial parties, with a marked mistrust towards the pharmaceutical industry. Most requested information needs related to data protection. Participants' ideal consent process would confer a range of options; for example, they would be able to choose with whom data can be shared, whether data will be de-identified or anonymous, the expiration date of their consent and how, if requested, general and personal study results would be disclosed. CONCLUSION: Our participants expressed clear information needs and a strong desire to be actively engaged in future data sharing decisions. Given that many researchers collaborate with commercial parties, building public confidence in these institutions would be beneficial. Illustrative examples addressing privacy concerns and clarifying difficult terms would aid consent decision-making. Although our participants displayed great altruism in sharing their data and accepted that broad consent would ultimately facilitate future research, broad consent did not reflect their ideal situation. Dynamic consent may be an option but warrants further feasibility research. PATIENT AND PUBLIC CONTRIBUTION: Women were recruited from the general breast cancer screening population. Their perceptions and information needs, as reported in this study, will not only inform broadened consent for PRISMA but ideally guide other consent templates and decisions regarding consent processes.