Automated rating of background parenchymal enhancement in MRI of extremely dense breasts without compromising the association with breast cancer in the DENSE trial.

OBJECTIVES: Background parenchymal enhancement (BPE) on dynamic contrast-enhanced MRI (DCE-MRI) as rated by radiologists is subject to inter- and intrareader variability. We aim to automate BPE category from DCE-MRI. METHODS: This study represents a secondary analysis of the Dense Tissue and Early Breast Neoplasm Screening trial. 4553 women with extremely dense breasts who received supplemental breast MRI screening in eight hospitals were included. Minimal, mild, moderate and marked BPE rated by radiologists were used as reference. Fifteen quantitative MRI features of the fibroglandular tissue were extracted to predict BPE using Random Forest, Naïve Bayes, and KNN classifiers. Majority voting was used to combine the predictions. Internal-external validation was used for training and validation. The inverse-variance weighted mean accuracy was used to express mean performance across the eight hospitals. Cox regression was used to verify non inferiority of the association between automated rating and breast cancer occurrence compared to the association for manual rating. RESULTS: The accuracy of majority voting ranged between 0.56 and 0.84 across the eight hospitals. The weighted mean prediction accuracy for the four BPE categories was 0.76. The hazard ratio (HR) of BPE for breast cancer occurrence was comparable between automated rating and manual rating (HR = 2.12 versus HR = 1.97, P = 0.65 for mild/moderate/marked BPE relative to minimal BPE). CONCLUSION: It is feasible to rate BPE automatically in DCE-MRI of women with extremely dense breasts without compromising the underlying association between BPE and breast cancer occurrence. The accuracy for minimal BPE is superior to that for other BPE categories.

Re-attendance in supplemental breast MRI screening rounds of the DENSE trial for women with extremely dense breasts.

OBJECTIVES: Supplemental MRI screening improves early breast cancer detection and reduces interval cancers in women with extremely dense breasts in a cost-effective way. Recently, the European Society of Breast Imaging recommended offering MRI screening to women with extremely dense breasts, but the debate on whether to implement it in breast cancer screening programs is ongoing. Insight into the participant experience and willingness to re-attend is important for this discussion. METHODS: We calculated the re-attendance rates of the second and third MRI screening rounds of the DENSE trial. Moreover, we calculated age-adjusted odds ratios (ORs) to study the association between characteristics and re-attendance. Women who discontinued MRI screening were asked to provide one or more reasons for this. RESULTS: The re-attendance rates were 81.3% (3458/4252) and 85.2% (2693/3160) in the second and third MRI screening round, respectively. A high age (> 65 years), a very low BMI, lower education, not being employed, smoking, and no alcohol consumption were correlated with lower re-attendance rates. Moderate or high levels of pain, discomfort, or anxiety experienced during the previous MRI screening round were correlated with lower re-attendance rates. Finally, a plurality of women mentioned an examination-related inconvenience as a reason to discontinue screening (39.1% and 34.8% in the second and third screening round, respectively). CONCLUSIONS: The willingness of women with dense breasts to re-attend an ongoing MRI screening study is high. However, emphasis should be placed on improving the MRI experience to increase the re-attendance rate if widespread supplemental MRI screening is implemented. CLINICAL RELEVANCE STATEMENT: For many women, MRI is an acceptable screening method, as re-attendance rates were high - even for screening in a clinical trial setting. To further enhance the (re-)attendance rate, one possible approach could be improving the overall MRI experience. KEY POINTS: • The willingness to re-attend in an ongoing MRI screening study is high. • Pain, discomfort, and anxiety in the previous MRI screening round were related to lower re-attendance rates. • Emphasis should be placed on improving MRI experience to increase the re-attendance rate in supplemental MRI screening.

Current use and future perspectives of contrast-enhanced mammography (CEM): a survey by the European Society of Breast Imaging (EUSOBI).

OBJECTIVES: To perform a survey among members of the European Society of Breast Imaging (EUSOBI) regarding the use of contrast-enhanced mammography (CEM). METHODS: A panel of nine board-certified radiologists developed a 29-item online questionnaire, distributed to all EUSOBI members (inside and outside Europe) from January 25 to March 10, 2023. CEM implementation, examination protocols, reporting strategies, and current and future CEM indications were investigated. Replies were exploratively analyzed with descriptive and non-parametric statistics. RESULTS: Among 434 respondents (74.9% from Europe), 50% (217/434) declared to use CEM, 155/217 (71.4%) seeing less than 200 CEMs per year. CEM use was associated with academic settings and high breast imaging workload (p < 0.001). The lack of CEM adoption was most commonly due to the perceived absence of a clinical need (65.0%) and the lack of resources to acquire CEM-capable systems (37.3%). CEM protocols varied widely, but most respondents (61.3%) had already adopted the 2022 ACR CEM BI-RADS® lexicon. CEM use in patients with contraindications to MRI was the most common current indication (80.6%), followed by preoperative staging (68.7%). Patients with MRI contraindications also represented the most commonly foreseen CEM indication (88.0%), followed by the work-up of inconclusive findings at non-contrast examinations (61.5%) and supplemental imaging in dense breasts (53.0%). Respondents declaring CEM use and higher CEM experience gave significantly more current (p = 0.004) and future indications (p < 0.001). CONCLUSIONS: Despite a trend towards academic high-workload settings and its prevalent use in patients with MRI contraindications, CEM use and progressive experience were associated with increased confidence in the technique. CLINICAL RELEVANCE STATEMENT: In this first survey on contrast-enhanced mammography (CEM) use and perspectives among the European Society of Breast Imaging (EUSOBI) members, the perceived absence of a clinical need chiefly drove the 50% CEM adoption rate. CEM adoption and progressive experience were associated with more extended current and future indications. KEY POINTS: • Among the 434 members of the European Society of Breast Imaging who completed this survey, 50% declared to use contrast-enhanced mammography in clinical practice. • Due to the perceived absence of a clinical need, contrast-enhanced mammography (CEM) is still prevalently used as a replacement for MRI in patients with MRI contraindications. • The number of current and future CEM indications marked by respondents was associated with their degree of CEM experience.

Image quality of DWI at breast MRI depends on the amount of fibroglandular tissue: implications for unenhanced screening.

OBJECTIVES: To compare image quality of diffusion-weighted imaging (DWI) and contrast-enhanced breast MRI (DCE-T1) stratified by the amount of fibroglandular tissue (FGT) as a measure of breast density. METHODS: Retrospective, multi-reader, bicentric visual grading analysis study on breast density (A-D) and overall image and fat suppression quality of DWI and DCE-T1, scored on a standard 5-point Likert scale. Cross tabulations and visual grading characteristic (VGC) curves were calculated for fatty breasts (A/B) versus dense breasts (C/D). RESULTS: Image quality of DWI was higher in the case of increased breast density, with good scores (score 3-5) in 85.9% (D) and 88.4% (C), compared to 61.6% (B) and 53.5% (A). Overall image quality of DWI was in favor of dense breasts (C/D), with an area under the VGC curve of 0.659 (p < 0.001). Quality of DWI and DCE-T1 fat suppression increased with higher breast density, with good scores (score 3-5) for 86.9% and 45.7% of density D, and 90.2% and 42.9% of density C cases, compared to 76.0% and 33.6% for density B and 54.7% and 29.6% for density A (DWI and DCE-T1 respectively). CONCLUSIONS: Dense breasts show excellent fat suppression and substantially higher image quality in DWI images compared with non-dense breasts. These results support the setup of studies exploring DWI-based MR imaging without IV contrast for additional screening of women with dense breasts. CLINICAL RELEVANCE STATEMENT: Our findings demonstrate that image quality of DWI is robust in women with an increased amount of fibroglandular tissue, technically supporting the feasibility of exploring applications such as screening of women with mammographically dense breasts. KEY POINTS: • Image and fat suppression quality of diffusion-weighted imaging are dependent on the amount of fibroglandular tissue (FGT) which is closely connected to breast density. • Fat suppression quality in diffusion-weighted imaging of the breast is best in women with a high amount of fibroglandular tissue. • High image quality of diffusion-weighted imaging in women with a high amount of FGT in MRI supports that the technical feasibility of DWI can be explored in the additional screening of women with mammographically dense breasts.

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.

Assessing Quantitative Parenchymal Features at Baseline Dynamic Contrast-enhanced MRI and Cancer Occurrence in Women with Extremely Dense Breasts.

Background Automated identification of quantitative breast parenchymal enhancement features on dynamic contrast-enhanced (DCE) MRI scans could provide added value in assessment of breast cancer risk in women with extremely dense breasts. Purpose To automatically identify quantitative properties of the breast parenchyma on baseline DCE MRI scans and assess their association with breast cancer occurrence in women with extremely dense breasts. Materials and Methods This study represents a secondary analysis of the Dense Tissue and Early Breast Neoplasm Screening trial. MRI was performed in eight hospitals between December 2011 and January 2016. After segmentation of fibroglandular tissue, quantitative features (including volumetric density, volumetric morphology, and enhancement characteristics) of the parenchyma were extracted from baseline MRI scans. Principal component analysis was used to identify parenchymal measures with the greatest variance. Multivariable Cox proportional hazards regression was applied to assess the association between breast cancer occurrence and quantitative parenchymal features, followed by stratification of significant features into tertiles. Results A total of 4553 women (mean age, 55.7 years ± 6 [SD]) with extremely dense breasts were included; of these women, 122 (3%) were diagnosed with breast cancer. Five principal components representing 96% of the variance were identified, and the component explaining the greatest independent variance (42%) consisted of MRI features relating to volume of enhancing parenchyma. Multivariable analysis showed that volume of enhancing parenchyma was associated with breast cancer occurrence (hazard ratio [HR], 1.09; 95% CI: 1.01, 1.18; P = .02). Additionally, women in the high tertile of volume of enhancing parenchyma showed a breast cancer occurrence twice that of women in the low tertile (HR, 2.09; 95% CI: 1.25, 3.61; P = .005). Conclusion In women with extremely dense breasts, a high volume of enhancing parenchyma on baseline DCE MRI scans was associated with increased occurrence of breast cancer as compared with a low volume of enhancing parenchyma. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

A survey by the European Society of Breast Imaging on radiologists' preferences regarding quality assurance measures of image interpretation in screening and diagnostic mammography.

OBJECTIVES: Quality assurance (QA) of image interpretation plays a key role in screening and diagnostic mammography, maintaining minimum standards and supporting continuous improvement in interpreting images. However, the QA structure across Europe shows considerable variation. The European Society of Breast Imaging (EUSOBI) conducted a survey among the members to collect information on radiologists' preferences regarding QA measures in mammography. MATERIALS AND METHODS: An anonymous online survey consisting of 25 questions was distributed to all EUSOBI members and national breast radiology bodies in Europe. The questions were designed to collect demographic characteristics, information on responders' mammography workload and data about QA measures currently used in their country. Data was analysed using descriptive statistical analysis, the χ2 test, linear regression, and Durbin-Watson statistic test. RESULTS: In total, 251 breast radiologists from 34 countries completed the survey. Most respondents were providing both screening and symptomatic services (137/251, 54.6%), working in an academic hospital (85/251, 33.9%) and reading 1000-4999 cases per year (109/251, 43.4%). More than half of them (133/251, 53%) had established QA measures in their workplace. Although less than one-third (71/251, 28.3%) had to participate in regular performance testing, the vast majority (190/251, 75.7%) agreed that a mandatory test would be helpful to improve their skills. CONCLUSION: QA measures were in place for more than half of the respondents working in screening and diagnostic mammography to evaluate their breast imaging performance. Although there were substantial differences between countries, the importance of having QA in the workplace and implemented was widely acknowledged by radiologists. CLINICAL RELEVANCE STATEMENT: Although several quality assurance (QA) measures of image interpretation are recommended by European bodies or national organisations, the QA in mammography is quite heterogenous between countries and reporting settings, and not always actively implemented across Europe. KEY POINTS: The first survey that presents radiologists' preferences regarding QA measures of image interpretation in mammography. Quality assurance measures in the workplace are better-established for breast screening compared to diagnostic mammography. Radiologists consider that performance tests would help to improve their mammography interpretation skills.

European Society of Breast Imaging (EUSOBI) guidelines on the management of axillary lymphadenopathy after COVID-19 vaccination: 2023 revision.

Axillary lymphadenopathy is a common side effect of COVID-19 vaccination, leading to increased imaging-detected asymptomatic and symptomatic unilateral axillary lymphadenopathy. This has threatened to negatively impact the workflow of breast imaging services, leading to the release of ten recommendations by the European Society of Breast Imaging (EUSOBI) in August 2021. Considering the rapidly changing scenario and data scarcity, these initial recommendations kept a highly conservative approach. As of 2023, according to newly acquired evidence, EUSOBI proposes the following updates, in order to reduce unnecessary examinations and avoid delaying necessary examinations. First, recommendation n. 3 has been revised to state that breast examinations should not be delayed or rescheduled because of COVID-19 vaccination, as evidence from the first pandemic waves highlights how delayed or missed screening tests have a negative effect on breast cancer morbidity and mortality, and that there is a near-zero risk of subsequent malignant findings in asymptomatic patients who have unilateral lymphadenopathy and no suspicious breast findings. Second, recommendation n. 7 has been revised to simplify follow-up strategies: in patients without breast cancer history and no imaging findings suspicious for cancer, symptomatic and asymptomatic imaging-detected unilateral lymphadenopathy on the same side of recent COVID-19 vaccination (within 12 weeks) should be classified as a benign finding (BI-RADS 2) and no further work-up should be pursued. All other recommendations issued by EUSOBI in 2021 remain valid.

Radiofrequency localization of nonpalpable breast cancer in a multicentre prospective cohort study: feasibility, clinical acceptability, and safety.

PURPOSE: In breast conserving surgery, accurate lesion localization is essential for obtaining adequate surgical margins. Preoperative wire localization (WL) and radioactive seed localization (RSL) are widely accepted methods to guide surgical excision of nonpalpable breast lesions but are limited by logistical challenges, migration issues, and legislative complexities. Radiofrequency identification (RFID) technology may offer a viable alternative. The purpose of this study was to evaluate the feasibility, clinical acceptability, and safety of RFID surgical guidance for localization of nonpalpable breast cancer. METHODS: In a prospective multicentre cohort study, the first 100 RFID localization procedures were included. The primary outcome was the percentage of clear resection margins and re-excision rate. Secondary outcomes included procedure details, user experience, learningcurve, and adverse events. RESULTS: Between April 2019 and May 2021, 100 women underwent RFID guided breast conserving surgery. Clear resection margins were obtained in 89 out of 96 included patients (92.7%), re-excision was indicated in three patients (3.1%). Radiologists reported difficulties with the placement of the RFID tag, partially related to the relatively large needle-applicator (12-gauge). This led to the premature termination of the study in the hospital using RSL as regular care. The radiologist experience was improved after a manufacturer modification of the needle-applicator. Surgical localization involved a low learning curve. Adverse events (n = 33) included dislocation of the marker during insertion (8%) and hematomas (9%). The majority of adverse events (85%) occurred using the first-generation needle-applicator. CONCLUSION: RFID technology is a potential alternative for non-radioactive and non-wire localization of nonpalpable breast lesions.

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.

Long-term Survival in Breast Cancer Patients Is Associated with Contralateral Parenchymal Enhancement at MRI: Outcomes of the SELECT Study.

Background Several single-center studies found that high contralateral parenchymal enhancement (CPE) at breast MRI was associated with improved long-term survival in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Due to varying sample sizes, population characteristics, and follow-up times, consensus of the association is currently lacking. Purpose To confirm whether CPE is associated with long-term survival in a large multicenter retrospective cohort, and to investigate if CPE is associated with endocrine therapy effectiveness. Materials and Methods This multicenter observational cohort included women with unilateral ER-positive HER2-negative breast cancer (tumor size ≤50 mm and ≤three positive lymph nodes) who underwent MRI from January 2005 to December 2010. Overall survival (OS), recurrence-free survival (RFS), and distant RFS (DRFS) were assessed. Kaplan-Meier analysis was performed to investigate differences in absolute risk after 10 years, stratified according to CPE tertile. Multivariable Cox proportional hazards regression analysis was performed to investigate whether CPE was associated with prognosis and endocrine therapy effectiveness. Results Overall, 1432 women (median age, 54 years [IQR, 47-63 years]) were included from 10 centers. Differences in absolute OS after 10 years were stratified according to CPE tertile as follows: 88.5% (95% CI: 88.1, 89.1) in tertile 1, 85.8% (95% CI: 85.2, 86.3) in tertile 2, and 85.9% (95% CI: 85.4, 86.4) in tertile 3. CPE was independently associated with OS, with a hazard ratio (HR) of 1.17 (95% CI: 1.0, 1.36; P = .047), but was not associated with RFS (HR, 1.11; P = .16) or DRFS (HR, 1.11; P = .19). The effect of endocrine therapy on survival could not be accurately assessed; therefore, the association between endocrine therapy efficacy and CPE could not reliably be estimated. Conclusion High contralateral parenchymal enhancement was associated with a marginally decreased overall survival in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer, but was not associated with recurrence-free survival (RFS) or distant RFS. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Honda and Iima in this issue.

Validation of Combined Deep Learning Triaging and Computer-Aided Diagnosis in 2901 Breast MRI Examinations From the Second Screening Round of the Dense Tissue and Early Breast Neoplasm Screening Trial.

OBJECTIVES: Computer-aided triaging (CAT) and computer-aided diagnosis (CAD) of screening breast magnetic resonance imaging have shown potential to reduce the workload of radiologists in the context of dismissing normal breast scans and dismissing benign disease in women with extremely dense breasts. The aim of this study was to validate the potential of integrating CAT and CAD to reduce workload and workup on benign lesions in the second screening round of the DENSE trial, without missing cancer. METHODS: We included 2901 breast magnetic resonance imaging scans, obtained from 8 hospitals in the Netherlands. Computer-aided triaging and CAD were previously developed on data from the first screening round. Computer-aided triaging dismissed examinations without lesions. Magnetic resonance imaging examinations triaged to radiological reading were counted and subsequently processed by CAD. The number of benign lesions correctly classified by CAD was recorded. The false-positive fraction of the CAD was compared with that of unassisted radiological reading in the second screening round. Receiver operating characteristics (ROC) analysis was performed and the generalizability of CAT and CAD was assessed by comparing results from first and second screening rounds. RESULTS: Computer-aided triaging dismissed 950 of 2901 (32.7%) examinations with 49 lesions in total; none were malignant. Subsequent CAD classified 132 of 285 (46.3%) lesions as benign without misclassifying any malignant lesion. Together, CAT and CAD yielded significantly fewer false-positive lesions, 53 of 109 (48.6%) and 89 of 109 (78.9%), respectively ( P = 0.001), than radiological reading alone. Computer-aided triaging had a smaller area under the ROC curve in the second screening round compared with the first, 0.83 versus 0.76 ( P = 0.001), but this did not affect the negative predictive value at the 100% sensitivity operating threshold. Computer-aided diagnosis was not associated with significant differences in area under the ROC curve (0.857 vs 0.753, P = 0.08). At the operating thresholds, the specificities of CAT (39.7% vs 41.0%, P = 0.70) and CAD (41.0% vs 38.2%, P = 0.62) were successfully reproduced in the second round. CONCLUSION: The combined application of CAT and CAD showed potential to reduce workload of radiologists and to reduce number of biopsies on benign lesions. Computer-aided triaging (CAT) correctly dismissed 950 of 2901 (32.7%) examinations with 49 lesions in total; none were malignant. Subsequent computer-aided diagnosis (CAD) classified 132 of 285 (46.3%) lesions as benign without misclassifying any malignant lesion. Together, CAT and CAD yielded significantly fewer false-positive lesions, 53 of 109 (48.6%) and 89 of 109 (78.9%), respectively ( P = 0.001), than radiological reading alone.

De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

BACKGROUND: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline. METHODS: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. FINDINGS: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. INTERPRETATION: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. FUNDING: Dutch Cancer Society. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

Evaluation of reader performance during interpretation of breast cancer screening: the Recall and detection Of breast Cancer in Screening (ROCS) trial study design.

The magnitude of the tradeoff between recall rate (RR) and cancer detection rate (CDR) in breast-cancer screening is not clear, and it is expected to depend on target population and screening program characteristics. Multi-reader multi-case research studies, which may be used to estimate this tradeoff, rely on enriched datasets with artificially high prevalence rates, which may bias the results. Furthermore, readers participating in research studies are subject to "laboratory" effects, which can alter their performance relative to actual practice. The Recall and detection Of breast Cancer in Screening (ROCS) trial uses a novel data acquisition system that minimizes these limitations while obtaining an estimate of the RR-CDR curve during actual practice in the Dutch National Breast Cancer Screening Program. ROCS involves collection of at least 40,000 probability-of-malignancy ratings from at least 20 radiologists during interpretation of approximately 2,000 digital mammography screening cases each. With the use of custom-built software on a tablet, and a webcam, this data was obtained in the usual reading environment with minimal workflow disruption and without electronic access to the review workstation software. Comparison of the results to short- and medium-term follow-up allows for estimation of the RR-CDR and receiver operating characteristics curves, respectively. The anticipated result of the study is that performance-based evidence from practice will be available to determine the optimal operating point for breast-cancer screening. In addition, this data will be useful as a benchmark when evaluating the impact of potential new screening technologies, such as digital breast tomosynthesis or artificial intelligence. KEY POINTS: • The ROCS trial aims to estimate the recall rate-cancer detection rate curve during actual screening practice in the Dutch National Breast Cancer Screening Program. • The study design is aimed at avoiding the influence of the "laboratory effect" in usual observer performance studies. • The use of a tablet and a webcam allows for the acquisition of probability of malignancy ratings without access to the review workstation software.

A multicenter prospective cohort study to evaluate feasibility of radio-frequency identification surgical guidance for nonpalpable breast lesions: design and rationale of the RFID Localizer 1 Trial.

BACKGROUND: Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. METHODS: This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. DISCUSSION: This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. TRIAL REGISTRATION: Netherlands National Trial Register, NL8019 , registered on September 12th 2019.

Breast cancer screening in women with extremely dense breasts recommendations of the European Society of Breast Imaging (EUSOBI).

Breast density is an independent risk factor for the development of breast cancer and also decreases the sensitivity of mammography for screening. Consequently, women with extremely dense breasts face an increased risk of late diagnosis of breast cancer. These women are, therefore, underserved with current mammographic screening programs. The results of recent studies reporting on contrast-enhanced breast MRI as a screening method in women with extremely dense breasts provide compelling evidence that this approach can enable an important reduction in breast cancer mortality for these women and is cost-effective. Because there is now a valid option to improve breast cancer screening, the European Society of Breast Imaging (EUSOBI) recommends that women should be informed about their breast density. EUSOBI thus calls on all providers of mammography screening to share density information with the women being screened. In light of the available evidence, in women aged 50 to 70 years with extremely dense breasts, the EUSOBI now recommends offering screening breast MRI every 2 to 4 years. The EUSOBI acknowledges that it may currently not be possible to offer breast MRI immediately and everywhere and underscores that quality assurance procedures need to be established, but urges radiological societies and policymakers to act on this now. Since the wishes and values of individual women differ, in screening the principles of shared decision-making should be embraced. In particular, women should be counselled on the benefits and risks of mammography and MRI-based screening, so that they are capable of making an informed choice about their preferred screening method. KEY POINTS: • The recommendations in Figure 1 summarize the key points of the manuscript.

Deep Learning for Automated Triaging of 4581 Breast MRI Examinations from the DENSE Trial.

Background Supplemental screening with MRI has proved beneficial in women with extremely dense breasts. Most MRI examinations show normal anatomic and physiologic variation that may not require radiologic review. Thus, ways to triage these normal MRI examinations to reduce radiologist workload are needed. Purpose To determine the feasibility of an automated triaging method using deep learning (DL) to dismiss the highest number of MRI examinations without lesions while still identifying malignant disease. Materials and Methods This secondary analysis of data from the Dense Tissue and Early Breast Neoplasm Screening, or DENSE, trial evaluated breast MRI examinations from the first screening round performed in eight hospitals between December 2011 and January 2016. A DL model was developed to differentiate between breasts with lesions and breasts without lesions. The model was trained to dismiss breasts with normal phenotypical variation and to triage lesions (Breast Imaging Reporting and Data System [BI-RADS] categories 2-5) using eightfold internal-external validation. The model was trained on data from seven hospitals and tested on data from the eighth hospital, alternating such that each hospital was used once as an external test set. Performance was assessed using receiver operating characteristic analysis. At 100% sensitivity for malignant disease, the fraction of examinations dismissed from radiologic review was estimated. Results A total of 4581 MRI examinations of extremely dense breasts from 4581women (mean age, 54.3 years; interquartile range, 51.5-59.8 years) were included. Of the 9162 breasts, 838 had at least one lesion (BI-RADS category 2-5, of which 77 were malignant) and 8324 had no lesions. At 100% sensitivity for malignant lesions, the DL model considered 90.7% (95% CI: 86.7, 94.7) of the MRI examinations with lesions to be nonnormal and triaged them to radiologic review. The DL model dismissed 39.7% (95% CI: 30.0, 49.4) of the MRI examinations without lesions. The DL model had an average area under the receiver operating characteristic curve of 0.83 (95% CI: 0.80, 0.85) in the differentiation between normal breast MRI examinations and MRI examinations with lesions. Conclusion Automated analysis of breast MRI examinations in women with dense breasts dismissed nearly 40% of MRI scans without lesions while not missing any cancers. ClinicalTrials.gov: NCT01315015 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Joe in this issue.

Added Value of Prereading Screening Mammograms for Breast Cancer by Radiologic Technologists on Early Screening Outcomes.

Background In the Dutch breast cancer screening program, mammograms are preread by technologists to identify possible abnormalities, leading to "warning signals" (an audible and visual alert if the technologist observed an abnormality suspicious for cancer) for radiologists. The best moment to present these warning signals is unknown. Purpose To determine the effect that blinding of technologists' warning signals has on radiologists' early screening outcome measures during interpretation of mammograms. Materials and Methods In this prospective study from September 2017 to May 2019, on alternating months, radiologists were either blinded or nonblinded to the warning signals of the technologist when interpreting screening mammograms for breast cancer. All discrepancies between radiologists and technologists were reviewed during quality assurance sessions every 6 weeks, which could result in secondary recalls. The outcome measures of this study were recall rate, cancer detection rate, and positive predictive value of recall. A χ2 test was used to test for differences between the two groups. Results During the study period, 109 596 women (mean age, 62 years ± 7 [standard deviation]), including 53 291 in the blinded and 56 305 in the nonblinded groups, participated. The overall recall rate (including secondary recalls) was lower for women in the blinded group than in the nonblinded group (blinded: 1140 of 53 291 women [2.1%], nonblinded: 1372 of 56 305 women [2.4%]; P = .001). There was no evidence of cancer detection rate differences between the groups (blinded: 349 of 53 291 women [6.5 per 1000 screening examinations], nonblinded: 360 of 56 305 women [6.4 per 1000 screening examinations]; P = .75). The blinded group thus had a higher positive predictive value of recall (blinded: 349 of 1140 women [30.6%], nonblinded: 360 of 1372 women [26.2%]; P = .02). Conclusion While interpreting screening mammograms for breast cancer, radiologists blinded to technologists' warning signals had lower recall rates with higher positive predictive values than nonblinded radiologists, yet cancer detection rates seemed to remain unchanged. See also the editorial by Hofvind and Lee in this issue. © RSNA, 2021.

Cost-Effectiveness of Magnetic Resonance Imaging Screening for Women With Extremely Dense Breast Tissue.

BACKGROUND: Extremely dense breast tissue is associated with increased breast cancer risk and limited sensitivity of mammography. The DENSE trial showed that additional magnetic resonance imaging (MRI) screening in women with extremely dense breasts resulted in a substantial reduction in interval cancers. The cost-effectiveness of MRI screening for these women is unknown. METHODS: We used the MISCAN-breast microsimulation model to simulate several screening protocols containing mammography and/or MRI to estimate long-term effects and costs. The model was calibrated using results of the DENSE trial and adjusted to incorporate decreases in breast density with increasing age. Screening strategies varied in the number of MRIs and mammograms offered to women ages 50-75 years. Outcomes were numbers of breast cancers, life-years, quality-adjusted life-years (QALYs), breast cancer deaths, and overdiagnosis. Incremental cost-effectiveness ratios (ICERs) were calculated (3% discounting), with a willingness-to-pay threshold of €22 000. RESULTS: Calibration resulted in a conservative fit of the model regarding MRI detection. Both strategies of the DENSE trial were dominated (biennial mammography; biennial mammography plus MRI). MRI alone every 4 years was cost-effective with €15 620 per QALY. Screening every 3 years with MRI alone resulted in an incremental cost-effectiveness ratio of €37 181 per QALY. All strategies with mammography and/or a 2-year interval were dominated because other strategies resulted in more additional QALYs per additional euro. Alternating mammography and MRI every 2 years was close to the efficiency frontier. CONCLUSIONS: MRI screening is cost-effective for women with extremely dense breasts, when applied at a 4-year interval. For a willingness to pay more than €22 000 per QALY gained, MRI at a 3-year interval is cost-effective as well.

Axillary lymphadenopathy at the time of COVID-19 vaccination: ten recommendations from the European Society of Breast Imaging (EUSOBI).

Unilateral axillary lymphadenopathy is a frequent mild side effect of COVID-19 vaccination. European Society of Breast Imaging (EUSOBI) proposes ten recommendations to standardise its management and reduce unnecessary additional imaging and invasive procedures: (1) in patients with previous history of breast cancer, vaccination should be performed in the contralateral arm or in the thigh; (2) collect vaccination data for all patients referred to breast imaging services, including patients undergoing breast cancer staging and follow-up imaging examinations; (3) perform breast imaging examinations preferentially before vaccination or at least 12 weeks after the last vaccine dose; (4) in patients with newly diagnosed breast cancer, apply standard imaging protocols regardless of vaccination status; (5) in any case of symptomatic or imaging-detected axillary lymphadenopathy before vaccination or at least 12 weeks after, examine with appropriate imaging the contralateral axilla and both breasts to exclude malignancy; (6) in case of axillary lymphadenopathy contralateral to the vaccination side, perform standard work-up; (7) in patients without breast cancer history and no suspicious breast imaging findings, lymphadenopathy only ipsilateral to the vaccination side within 12 weeks after vaccination can be considered benign or probably-benign, depending on clinical context; (8) in patients without breast cancer history, post-vaccination lymphadenopathy coupled with suspicious breast finding requires standard work-up, including biopsy when appropriate; (9) in patients with breast cancer history, interpret and manage post-vaccination lymphadenopathy considering the timeframe from vaccination and overall nodal metastatic risk; (10) complex or unclear cases should be managed by the multidisciplinary team.