Linda Appelman’s research while affiliated with Radboud University Medical Centre (Radboudumc) and other places

Objectives The breast ultrasound trial (BUST) demonstrates a high negative predictive value of ultrasound for women presenting with focal breast complaints, suggesting a potential shift from mammography/digital breast tomosynthesis (DBT) to ultrasound as a primary imaging modality. This BUST side-study explored women’s perspectives on adopting ultrasound as the primary diagnostic tool. Methods Twenty-nine female BUST participants (mean age = 48.4, SD = 8.3) with benign findings after diagnostic evaluation participated in one of six focus group interviews 18–24 months post-imaging. Discussions were transcribed and analyzed thematically. Results Four overarching themes were identified; personal health situation, organization of breast care, effectiveness of imaging, and professionals’ attitudes and roles. Participants considered their own health history and complaint type (personal health situation) and discussed eligibility for national screening programs and the costs of both exams (organization of breast care). Opinions varied on the effectiveness of imaging, particularly regarding the importance of detecting additional non-symptomatic findings with mammography/DBT that may be missed by ultrasound. Concerns were also raised about implementing research findings without conclusive scientific evidence. Health professionals’ attitudes and roles encompassed the influence of GPs’ and radiologists’ attitudes and the process of image interpretation. Conclusion These findings reveal diverse attitudes of women towards ultrasound as a primary modality, warranting caution when transitioning to new clinical standards. Providing comprehensive information about the evidence on the benefits and risks of different imaging modalities is essential, and fostering shared decision-making could enhance acceptance. Offering women the choice of additional imaging, such as mammography/DBT after an initial ultrasound, may balance clinical performance with patient autonomy. Critical relevance statement Patients’ perspectives on medical procedures are increasingly significant in modern healthcare. Women’s perceived barriers and facilitators to diagnostic imaging, shaped by numerous factors, offer healthcare professionals insights beyond pure biomedical approaches, fostering shared decision-making within radiology and other clinical contexts. Key Points This study explores women’s perspectives on breast ultrasound as a primary imaging modality. Attitudes towards an ultrasound-first approach are shaped by internal and external considerations. Considerations are highly informed by emotional responses and lack of knowledge. Insights into women’s perspectives inform healthcare professionals and foster shared decision-making within radiology. Graphical Abstract

Introduction The high diagnostic accuracy of ultrasound opens possibilities to shift towards an initial ultrasound approach for the evaluation of focal breast complaints in women, with only additional DBT in case of unclear or suspicious ultrasound findings. As general practitioners (GPs) are important stakeholders in the diagnostic pathway, this study focuses on GPs perspective on ultrasound as primary diagnostic imaging test, as well as the GP referral process. Methods Sixteen Dutch GPs were interviewed on the referral process and their perceived barriers and facilitators of initial ultrasound diagnostics in women presenting with focal breast complaints. Interview data were transcribed verbatim and analyzed thematically. Results Thematic analysis identified themes related to 1) the routine breast consult (consult characteristics, referral decision, referral rationale and diagnostic imaging decision) and 2) considerations of an ultrasound-only approach. Regarding the latter, the theme diagnostic workflow emphasizes GPs concerns regarding long waiting times for ultrasound. Professional communication describes communicational barriers on patient-radiologist and radiologist-GP level. In the theme doctor-patient relationship shared decision-making was highlighted, while concerns existed on the lack of patient return to the GP after result disclosure at the hospital. Effectiveness of imaging is associated with GPs’ acceptance of the diagnostic performance of ultrasound as stand-alone modality. Personal expertise and workload is related to consequences of an initial ultrasound approach on GPs workload and professional tasks. Regarding the patient benefit-harm trade-off, various patient (dis)advantages were highlighted. Decentralization of diagnostic evaluation was considered a potential practical implication of ultrasound as primary diagnostic test. Conclusion Participants seemed to welcome ultrasound-only diagnostics for the evaluation of women's focal breast complaints, emphasizing multiple benefits for both the patients and GPs. They, however, also addressed various challenges that should be taken into consideration when actually practicing an initial ultrasound approach.

Background Although DBT is the standard initial imaging modality for women with focal breast symptoms, the importance of ultrasound has grown rapidly in the past decades. Therefore, the Breast UltraSound Trial (BUST) focused on assessing the diagnostic value of ultrasound and digital breast tomosynthesis (DBT) for the evaluation of breast symptoms by reversing the order of breast imaging; first performing ultrasound followed by DBT. This side-study of the BUST evaluates patients’ perceptions of ultrasound and DBT in a reversed setting. Methods After imaging, 1181/1276 BUST participants completed a survey consisting of open and closed questions regarding both exams (mean age 47.2, ±11.74). Additionally, a different subset of BUST participants (n = 29) participated in six focus group interviews 18–24 months after imaging to analyze their imaging experiences in depth. Results A total of 55.3% of women reported reluctance to undergoing DBT, primarily due of pain, while the vast majority also find bilateral DBT reassuring (87.3%). Thematic analysis identified themes related to 1) imaging reluctance (pain/burden, result, and breast harm) and 2) ultrasound and DBT perceptions. Regarding the latter, the theme comfort underscores DBT as burdensome and painful, while ultrasound is largely perceived as non-burdensome. Ultrasound is also particularly valued for its interactive nature, as highlighted in the theme interaction. Perceived effectiveness reflects women’s interest in bilateral breast evaluation with DBT and the visibility of lesions, while they express more uncertainty about the reliability of ultrasound. Emotional impact portrays DBT as reassuring for many women, whereas opinions on the reassurance provided by ultrasound are more diverse. Additional themes include costs, protocols and privacy. Conclusions Ultrasound is highly tolerated, and particularly valued is the interaction with the radiologist. Nearly half of women express reluctance towards DBT; nevertheless, a large portion report feeling more confident after undergoing bilateral DBT, reassuring them of the absence of abnormalities. Understanding patients’ perceptions of breast imaging examinations is of great value when optimizing diagnostic pathways.

Breast complaints are frequent reasons for consultations in primary care or breast clinics. Breast pain, breast lumps, and nipple discharge are the most common complaints. Less common symptoms such as skin changes and axillary abnormalities also require specific diagnostic approaches. Imaging the symptomatic breast should be performed by appropriately trained breast radiologists following the best practice guidelines and quality standards. Full-field digital mammography (FFDM), digital breast tomosynthesis (DBT), and breast ultrasound (US) are the main modalities used in this primary setting. The choice depends on the patient's age and symptoms. Women younger than 30-years-old are first imaged by US, whereas women over 40-years-old usually require both FFDM or DBT and US. For women between 30-years-old and 40-years-old, the US is the modality of choice, whereas FFDM or DBT might also be performed if needed. Pregnant or lactating women with palpable lesions or nipple discharge are imaged with US as the first method; FFDM or DBT can also be performed depending on the degree of suspicion as the dose to the fetus is minimal, and shielding may even further reduce the dose. More advanced techniques such as breast magnetic resonance imaging or contrast-enhanced mammography are not indicated in this first diagnostic setting and are reserved for cases of established malignancy (local staging) or rare cases of equivocal findings not otherwise resolved or inflammatory breast cancer. Last, but not least, male breast symptoms should also be addressed with US and/or FFDM. CLINICAL RELEVANCE STATEMENT: It is equally important to correctly diagnose an underlying malignancy and to avoid false positives that would lead to unnecessary biopsies, increased costs, and anxiety for the patient. Proper use of imaging modalities ensures optimal diagnostic approach and minimizes false negatives. KEY POINTS: Ultrasound, full-field digital mammography, or digital breast tomosynthesis are the main imaging modalities in the diagnostic setting, while MRI or contrast-enhanced mammography should be reserved to selected cases. Initial imaging modality includes ultrasound combined with mammography or digital breast tomosynthesis depending on women's age and the presence (or not) of inconclusive findings. A negative imaging evaluation should not deter biopsy when a highly suspicious finding is found on physical examination.

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.

Objectives To assess the diagnostic performance of 3D automated breast ultrasound (3D-ABUS) in breast cancer screening in a clinical setting. Materials and methods All patients who had 3D-ABUS between January 2014 and January 2022 for screening were included in this retrospective study. The images were reported by 1 of 6 breast radiologists based on the Breast Imaging Reporting and Data Systems (BI-RADS). The 3D-ABUS was reviewed together with the digital breast tomosynthesis (DBT). Recall rate, biopsy rate, positive predictive value (PPV) and cancer detection yield were calculated. Results In total, 3616 studies were performed in 1555 women (breast density C/D 95.5% ( n = 3455/3616), breast density A/B 4.0% ( n = 144/3616), density unknown (0.5% ( n = 17/3616)). A total of 259 lesions were detected on 3D-ABUS (87.6% ( n = 227/259) masses and 12.4% ( n = 32/259) architectural distortions). The recall rate was 5.2% ( n = 188/3616) (CI 4.5–6.0%) with only 36.7% ( n = 69/188) cases recalled to another date. Moreover, recall declined over time. There were 3.4% ( n = 123/3616) biopsies performed, with 52.8% ( n = 65/123) biopsies due to an abnormality detected in 3D-ABUS alone. Ten of 65 lesions were malignant, resulting in a positive predictive value (PPV) of 15.4% ( n = 10/65) (CI 7.6–26.5%)). The cancer detection yield of 3D-ABUS is 2.77 per 1000 screening tests (CI 1.30–5.1). Conclusion The cancer detection yield of 3D-ABUS in a real clinical screening setting is comparable to the results reported in previous prospective studies, with lower recall and biopsy rates. 3D-ABUS also may be an alternative for screening when mammography is not possible or declined. Clinical relevance statement 3D automated breast ultrasound screening performance in a clinical setting is comparable to previous prospective studies, with better recall and biopsy rates. Key Points • 3D automated breast ultrasound is a reliable and reproducible tool that provides a three-dimensional representation of the breast and allows image visualisation in axial, coronal and sagittal. • The diagnostic performance of 3D automated breast ultrasound in a real clinical setting is comparable to its performance in previously published prospective studies, with improved recall and biopsy rates. • 3D automated breast ultrasound is a useful adjunct to mammography in dense breasts and may be an alternative for screening when mammography is not possible or declined.

Objectives This project aims to model an optimal scanning environment for breast magnetic resonance imaging (MRI) screening based on real-life data to identify to what extent the logistics of breast MRI can be optimized. Materials and Methods A novel concept for a breast MRI screening facility was developed considering layout of the building, workflow steps, used resources, and MRI protocols. The envisioned screening facility is person centered and aims for an efficient workflow-oriented design. Real-life data, collected from existing breast MRI screening workflows, during 62 scans in 3 different hospitals, were imported into a 3D simulation software for designing and testing new concepts. The model provided several realistic, virtual, logistical pathways for MRI screening and their outcome measures: throughput, waiting times, and other relevant variables. Results The total average appointment time in the baseline scenario was 25:54 minutes, with 19:06 minutes of MRI room occupation. Simulated improvements consisted of optimizing processes and resources, facility layout, and scanning protocol. In the simulation, time spent in the MRI room was reduced by introducing an optimized facility layout, dockable tables, and adoption of an abbreviated MRI scanning protocol. The total average appointment time was reduced to 19:36 minutes, and in this scenario, the MRI room was occupied for 06:21 minutes. In the most promising scenario, screening of about 68 people per day (10 hours) on a single MRI scanner could be feasible, compared with 36 people per day in the baseline scenario. Conclusions This study suggests that by optimizing workflow MRI for breast screening total appointment duration and MRI occupation can be reduced. A throughput of up to 6 people per hour may be achieved, compared with 3 people per hour in the current setup.

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.

Accurately determining the molecular subtypes of breast cancer is important for the prognosis of breast cancer patients and can guide treatment selection. In this study, we develop a deep learning-based model for predicting the molecular subtypes of breast cancer directly from the diagnostic mammography and ultrasound images. Multi-modal deep learning with intra- and inter-modality attention modules (MDL-IIA) is proposed to extract important relations between mammography and ultrasound for this task. MDL-IIA leads to the best diagnostic performance compared to other cohort models in predicting 4-category molecular subtypes with Matthews correlation coefficient (MCC) of 0.837 (95% confidence interval [CI]: 0.803, 0.870). The MDL-IIA model can also discriminate between Luminal and Non-Luminal disease with an area under the receiver operating characteristic curve of 0.929 (95% CI: 0.903, 0.951). These results significantly outperform clinicians’ predictions based on radiographic imaging. Beyond molecular-level test, based on gene-level ground truth, our method can bypass the inherent uncertainty from immunohistochemistry test. This work thus provides a noninvasive method to predict the molecular subtypes of breast cancer, potentially guiding treatment selection for breast cancer patients and providing decision support for clinicians.

Background: The high diagnostic performance of modern breast ultrasound (US) opens the possibility to shift toward targeted US as initial imaging test in women with breast complaints. This comparative cohort study investigates the effects of starting with US followed by digital breast tomosynthesis (DBT), as practiced in the breast ultrasound study (BUST), on women's health-related quality of life (QoL). Methods: Fifty BUST participants and 50 "controls" who underwent DBT and US in regular order filled out the EQ-5D-3L three times during their visit: BUST participants before US (T1), after US (T2), and after DBT (T3) and non-BUST participants before DBT (T1), after DBT (T2), and after US (T3). Changes in QoL from baseline to T2 and T3 were assessed using generalized least squares, also taking into account the effects of biopsy, age, and complaint type. Results: Participants' mean age was 50.6 years (BUST: SD = 12.1, controls: SD = 11.5). At T2 the overall QoL was higher [t(102.9) = 2.4, p = 0.017] and anxiety levels were lower [t(98.7) = -2.4, p = 0.020] in BUST participants compared with controls. However, from T2 to T3 these effects equalize, resulting in similar performances in QoL and anxiety at T3, respectively [t(97.6) = -2.3, p = 0.023] and [t(97.2) = 3.1, p = 0.002]. Compared with BUST participants, controls show a clear decrease in pain after US [t(106.5) = -2.8, p = 0.006]. Women undergoing biopsy had lower QoL [t(167.1) = -2.4, p = 0.017] and pain [t(154.1) = -2.1, p = 0.038], and more anxiety [t(187.4) = 4.3, p = 0.000]. Conclusions: The results suggest that changing the radiological order by starting with US has a short-term positive effect on overall QoL, anxiety, and DBT pain experience in symptomatic women. Owing to its negative impact, biopsies should be performed cautiously. In conclusion, the moment of reassurance for women advances by reversing the radiological order according to the BUST, showing the high importance of human interaction in diagnostic care in addition to the clinical performance of imaging modalities.