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Purpose: To compare mammography, breast ultrasound (US), high-resolution diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced breast MRI (DCE-MRI), and their combinations for detecting clinically occult early breast cancers (EBCs), including ductal carcinoma in situ (DCIS)., Methods: Three hundred and three consecutive women with screening imaging-detected early breast cancers (60 pure DCIS, 36 DCIS with microinvasion, and 207 invasive carcinoma less than 20 mm) who underwent breast MRI at 3 T including DW-MRI (b-values of 0, 800 and 1200 s/mm 2 ; in-plane resolution, 1.1 × 1.1 mm 2 or 1.3 × 1.3 mm 2 ; section thickness, 3 mm) were retrospectively reviewed. Three radiologists independently reviewed each examination. Statistical analysis included Chi-square test, McNemar test for comparison of cancer detection rates, and Fleiss' Kappa for interreader agreement. Mixed-effect logistic regression analysis was employed to evaluate factors associated with cancer detection on DW-MRI., Results: The overall cancer detection rates were 54.8% on mammography, 71.0% on breast US, 81.5% on DW-MRI, and 87.1% on DCE-MRI. On McNemar test, DW-MRI detected more cancers than mammography (adjusted p < 0.001), and its combination with mammography showed a similar cancer detection rate to DCE-MRI combined with mammography (adjusted p = 0.808). On multivariable analysis, histologic type, lesion size, ADC and CNR on DW-MRI were independent factors for cancer detection on DW-MRI. The interreader agreement for cancer detection was moderate to substantial (Fleiss' kappa: 0.52-0.65) across each modality., Conclusion: High-resolution DW-MRI plus mammography showed comparable cancer detection rate to DCE-MRI plus mammography for detecting clinically occult EBCs including DCIS., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: This retrospective study received approval from the Institutional Review Board of our institution and was performed in accordance with the relevant guidelines and regulations. The requirement for informed patient consent was waived., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

BACKGROUND. China has faced barriers to implementation of a population-based mammographic screening program. Breast ultrasound provides an alternative screening modality to mammography in low-resource settings. OBJECTIVE. The purpose of this study was to evaluate the performance of automated breast ultrasound (ABUS) with remote reading as the primary screening modality for breast cancer. METHODS. This prospective study enrolled asymptomatic women 35-69 years old from 46 community health centers across 18 provinces representing all six regions of China from January 2021 to December 2021. Participants underwent screening ABUS as the sole breast cancer screening modality, with images acquired by a technologist at a community health center. The 3D volumetric data were transferred via cloud-based software to a single remote reading center, where examinations were interpreted independently in batches by two subspecialized breast radiologists using BI-RADS; a third radiologist at the remote reading center resolved discrepancies. Diagnostic reports were returned to the community centers, and patients sought follow-up care at local hospitals. The reference standard incorporated a combination of histopathology and 24-month follow-up. Outcome measures included cancer detection rate, abnormal interpretation rate (AIR), sensitivity, specificity, biopsy rate, and PPV. RESULTS. The final analysis included 5978 enrolled participants (median age, 46 years [IQR, 40-52 years]) who underwent screening ABUS at the community health centers with subsequent remote reading. A total of 24 ABUS-detected cancers and two interval cancers were diagnosed. The cancer detection rate was 4.0 per 1000 women (95% CI: 2.7-5.9), and the AIR was 11.9% (95% CI: 11.1-12.7%). A total of 95.8% (23/24) of ABUS-detected cancers were invasive. The 23 invasive cancers had a median diameter of 10.0 mm, and 73.9% (17/23) were node-negative. Sensitivity was 92.3% (95% CI: 75.9-97.9%), and specificity was 88.4% (95% CI: 87.6-89.2%). The biopsy rate was 1.7% (95% CI: 1.4-2.0%), and the PPV of biopsy was 24.0% (95% CI: 16.7-33.2%). CONCLUSION. ABUS screening with remote reading met benchmark performance for cancer detection in comparison with mammography, with infrequent interval cancers. CLINICAL IMPACT. ABUS with remote reading holds promise in enhancing access to breast cancer screening and early detection in low-resource settings or underserved regions where mammographic screening is not established. TRIAL REGISTRATION. ClinicalTrials.gov NCT04527510.

Background Breast nonmass lesions (NMLs) are observed at screening and diagnostic US. However, knowledge is limited on imaging features of NMLs at screening US. Purpose To identify features of NMLs at screening US that are suspicious for malignancy based on mammographic findings. Materials and Methods This retrospective, multicenter study included asymptomatic women who underwent screening US between January 2012 and December 2019. Eligible women had NMLs at US, concurrent screening mammography, and record of a final diagnosis. Logistic regression analyses were used to identify factors associated with malignancy. The diagnostic performance of each sonographic feature according to mammographic findings was calculated. A reader study was performed to assess interreader agreement for sonographic features. Results Among 993 NMLs in 993 patients (mean age, 50 years ± 9 [SD]), 914 (92.0%) were benign and 79 (8.0%) were malignant. Mean size was larger for malignant NMLs than for benign NMLs (2.6 cm ± 1.1 vs 1.9 cm ± 0.8; P < .001). In multivariable analysis, associated calcifications (odds ratio [OR], 21.6 [95% CI: 8.0, 58.2]; P < .001), posterior shadowing (OR, 6.9 [95% CI: 2.6, 18.4]; P < .001), segmental distribution (OR, 6.2 [95% CI: 2.7, 14.4]; P < .001), mixed echogenicity (OR, 5.0 [95% CI: 1.8, 14.0]; P < .001), and size (OR, 1.5 [95% CI: 1.1, 2.1]; P = .01) at US were associated with malignancy. Associated calcifications, posterior shadowing, segmental distribution, and mixed echogenicity showed positive predictive values (PPVs) of 44%, 22%, 22.9%, and 16.6%, respectively. Having a negative mammogram was associated with a lower malignancy rate (2.8% vs 28.8%) and lower PPVs for sonographic features (0.7%-10.4% vs 24%-55%) than having a positive mammogram. Interreader agreement for sonographic features was good to excellent (Fleiss κ 95% CI lower bound range, 0.63-0.81). Conclusion Calcifications, posterior shadowing, segmental distribution, and mixed echogenicity associated with NMLs can be considered suspicious features for malignancy at screening US. As malignancy rates and PPVs differ according to mammographic abnormalities, combined assessment is mandatory. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Grimm in this issue.

The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMT SB2-/- ) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMT WT ) mice, PyMT SB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMT SB2-/- tumors. Decreased CD206 + M2 and increased NOS2 + M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMT SB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMT WT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization., (© 2024. The Author(s).)

Rationale and Objectives: Little is known about the factors affecting the Artificial Intelligence (AI) software performance on mammography for breast cancer detection. This study was to identify factors associated with abnormality scores assigned by the AI software., Materials and Methods: A retrospective database search was conducted to identify consecutive asymptomatic women who underwent breast cancer surgery between April 2016 and December 2019. A commercially available AI software (Lunit INSIGHT, MMG, Ver. 1.1.4.0) was used for preoperative mammography to assign individual abnormality scores to the lesions and score of 10 or higher was considered as positive detection by AI software. Radiologists without knowledge of the AI results retrospectively assessed the mammographic density and classified mammographic findings into positive and negative finding. General linear model (GLM) analysis was used to identify the clinical, pathological, and mammographic findings related to the abnormality scores, obtaining coefficient β values that represent the mean difference per unit or comparison with the reference value. Additionally, the reasons for non-detection by the AI software were investigated., Results: Among the 1001 index cancers (830 invasive cancers and 171 ductal carcinoma in situs) in 1001 patients, 717 (72%) were correctly detected by AI, while the remaining 284 (28%) were not detected. Multivariable GLM analysis showed that abnormal mammography findings (β = 77.0 for mass, β = 73.1 for calcification only, β = 49.4 for architectural distortion, and β = 47.6 for asymmetry compared to negative; all Ps < 0.001), invasive tumor size (β = 4.3 per 1 cm, P < 0.001), and human epidermal growth receptor type 2 (HER2) positivity (β = 9.2 compared to hormone receptor positive, HER2 negative, P = 0.004) were associated with higher mean abnormality score. AI failed to detect small asymmetries in extremely dense breasts, subcentimeter-sized or isodense lesions, and faint amorphous calcifications., Conclusion: Cancers with positive abnormal mammographic findings on retrospective review, large invasive size, HER2 positivity had high AI abnormality scores. Understanding the patterns of AI software performance is crucial for effectively integrating AI into clinical practice., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung Min Chang reports was provided by Seoul National University Hospital., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women., Materials and Methods: Seven healthy premenopausal women (median age, 37 years; range, 33-49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm² (b800), 1200 sec/mm² (b1200), and a synthetic 1500 sec/mm² (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADC BPS ) and fibroglandular tissue (ADC FGT ). Changes in the visual grade, BPS volume (%), ADC BPS , and ADC FGT during the menstrual cycle were descriptively analyzed., Results: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADC BPS in the EFP. Four of the seven volunteers showed the highest ADC BPS in the early luteal phase (ELP) and the lowest ADC FGT in the late follicular phase (LFP)., Conclusion: Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADC BPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADC BPS was more common in ELP. The lowest ADC FGT was more frequent in LFP., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Purpose: To compare the performance of mammography, high-resolution DW-MRI, DCE-MRI, and their combinations in detecting clinically occult breast cancer in women with dense breasts., Method: 544 breasts from 281 consecutive asymptomatic women with dense breasts were retrospectively identified. They underwent breast MRI for preoperative evaluation of breast cancers (n = 214) or as supplemental screening (n = 67) including DCE-MRI and DW-MRI (b values, 0 and 1000 sec/mm 2 ; in-plane resolution, 1.1 × 1.1 mm 2 and 1.3 × 1.3 mm 2 ; section thickness, 3 mm), in addition to mammography. Three readers independently reviewed each examination on a per-breast basis. Histopathology and at least two year of imaging follow-up served as the gold standard. The sensitivities and specificities of different imaging modalities were compared using McNemar test., Results: 230 of 544 breasts (42 %) had malignant lesions. The sensitivity of DW-MRI was higher than that of mammography (77.0 % vs 57.9 %; adjusted p < 0.001), but lower than that of DCE-MRI (84.8 %; adjusted p = 0.014). The specificity of DW-MRI was comparable to those of mammography (98.1 % vs 99.1 %; adjusted p > 0.999) and DCE-MRI (97.1 %; adjusted p > 0.999). DW-MRI plus mammography had a comparable sensitivity and specificity to those of DCE-MRI plus mammography (88.6 % vs 90.9 % and 97.1 % vs 96.2 %; adjusted p > 0.999 for both)., Conclusions: High-resolution DW-MRI had a sensitivity higher than mammography and lower than DCE-MRI. Nevertheless, DW-MRI plus mammography showed a comparable sensitivity and specificity to DCE-MRI plus mammography for detecting clinically occult cancers in women with dense breasts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the association of mammographic breast density with treatment and survival outcomes in patients with triple-negative breast cancer (TNBC) undergoing neoadjuvant chemotherapy (NAC)., Methods: This retrospective study evaluated 306 women with TNBC who underwent NAC followed by surgery between 2010 and 2019. The baseline density and the density changes after NAC were evaluated. Qualitative breast density (a-d) was evaluated using the Breast Imaging Reporting and Data System. Quantitative breast density (%) was evaluated using fully automated software (the Laboratory for Individualized Breast Radiodensity Assessment) in the contralateral breast. Multivariable logistic regression analysis was used to evaluate the association between breast density and pathologic complete response (pCR), stratified by menopausal status. Cox proportional hazard regression analysis was used to evaluate the association among breast density, the development of contralateral breast cancer, and the development of locoregional recurrence and/or distant metastasis., Results: Contralateral density reduction ≥10 % was independently associated with pCR in premenopausal women (odds ratio [OR], 2.5; p = 0.022) but not in postmenopausal women (OR, 0.9; p = 0.823). During a mean follow-up of 65 months, 10 (3 %) women developed contralateral breast cancer, and 68 (22 %) women developed locoregional recurrences and/or distant metastases. Contralateral density reduction ≥10 % showed no association with the occurrence of contralateral breast cancer (hazard ratio [HR], 3.1; p = 0.308) or with locoregional recurrence and/or distant metastasis (HR, 1.1; p = 0.794)., Conclusion: In premenopausal women, a contralateral breast density reduction of ≥10 % after NAC was independently associated with pCR, although it did not translate into improved outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the clinical and imaging factors associated with hemorrhagic complications and patient discomfort following ultrasound (US)-guided breast biopsy., Materials and Methods: We prospectively enrolled 94 patients who were referred to our hospital between June 2022 and December 2022 for US-guided breast biopsy. After obtaining informed consent, two breast radiologists independently performed US-guided breast biopsy and evaluated the imaging findings. A hemorrhagic complication was defined as the presence of bleeding or hematoma on US. The patients rated symptoms of pain, febrile sensation, swelling at the biopsy site, and dyspnea immediately, 20 minutes, and 2 weeks after the procedure on a visual analog scale, with 0 for none and 10 for the most severe symptoms. Additional details recorded included those of nausea, vomiting, bleeding, bruising, and overall satisfaction score. We compared the clinical symptoms, imaging characteristics, and procedural features between patients with and those without hemorrhagic complications., Results: Of 94 patients, 7 (7%) developed hemorrhagic complications, while 87 (93%) did not. The complication resolved with 20 minutes of manual compression, and no further intervention was required. Vascularity on Doppler examination ( P = 0.008), needle type ( P = 0.043), and lesion location ( P < 0.001) were significantly different between the groups. Patients with hemorrhagic complications reported more frequent nausea or vomiting than those without hemorrhagic complications (29% [2/7] vs. 2% [2/87], respectively; P = 0.027). The overall satisfaction scores did not differ between the two groups ( P = 0.396). After 2 weeks, all symptoms subsided, except bruising (50% 2/4 in the complication group and 25% [16/65] in the no-complication group)., Conclusion: US-guided breast biopsy is a safe procedure with a low complication rate. Radiologists should be aware of hemorrhagic complications, patient discomfort, and overall satisfaction related to this procedure., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Abnormalities on breast ultrasound (US) images which do not meet the criteria for masses are referred to as nonmass lesions. These features and outcomes have been investigated in several studies conducted by Asian researchers. However, the term "nonmass" is not included in the American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) 5th edition for US. According to the Japan Association of Breast and Thyroid Sonology guidelines, breast lesions are divided into mass and nonmass. US findings of nonmass abnormalities are classified into five subtypes: abnormalities of the ducts, hypoechoic areas in the mammary glands, architectural distortion, multiple small cysts, and echogenic foci without a hypoechoic area. These findings can be benign or malignant; however, focal or segmental distributions and presence of calcifications suggest malignancy. Intraductal, invasive ductal, and lobular carcinomas can present as nonmass abnormalities. For the nonmass concept to be included in the next BI-RADS and be widely accepted in clinical practice, standardized terminologies, an interpretation algorithm, and outcome-based evidence are required for both screening and diagnostic US., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 The Korean Society of Radiology.)

Nonmass lesions (NMLs) on breast US are defined as discrete areas of altered echotexture compared to surrounding breast tissue and lack the 3-dimensionality of a mass. They are not a component of American College of Radiology BI-RADS, but they are a finding type included in the Japan Association of Breast and Thyroid Sonology lexicon. Use of the NML finding is routine in many Asian practices, including the Samsung Medical Center and Seoul National University Hospital, and their features and outcomes have been investigated in multiple studies. Nonmass lesions are most often observed when US is used to evaluate mammographic asymmetries, suspicious calcifications, and nonmass enhancement on MRI and contrast-enhanced mammography. Nonmass lesions can be described by their echogenicity, distribution, presence or absence of associated calcifications, abnormal duct changes, architectural distortion, posterior shadowing, small cysts, and hypervascularity. Malignant lesions, especially ductal carcinoma in situ, can manifest as NMLs on US. There is considerable overlap between the US features of benign and malignant NMLs, and they also must be distinguished from normal variants. The literature indicates that NMLs with linear or segmental distribution, associated calcifications, abnormal duct changes, posterior shadowing, and hypervascularity are suggestive of malignancy, whereas NMLs with only interspersed small cysts are usually benign fibrocystic changes. In this article, we introduce the concepts of NMLs, illustrate US features suggestive of benign and malignant etiologies, and discuss our institutional approach for evaluating NMLs and an algorithm that we use to guide interpretation in clinical practice., (© Society of Breast Imaging 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate whether reader training improves the performance and agreement of radiologists in interpreting unenhanced breast magnetic resonance imaging (MRI) scans using diffusion-weighted imaging (DWI)., Materials and Methods: A study of 96 breasts (35 cancers, 24 benign, and 37 negative) in 48 asymptomatic women was performed between June 2019 and October 2020. High-resolution DWI with b-values of 0, 800, and 1200 sec/mm² was performed using a 3.0-T system. Sixteen breast radiologists independently reviewed the DWI, apparent diffusion coefficient maps, and T1-weighted MRI scans and recorded the Breast Imaging Reporting and Data System (BI-RADS) category for each breast. After a 2-h training session and a 5-month washout period, they re-evaluated the BI-RADS categories. A BI-RADS category of 4 (lesions with at least two suspicious criteria) or 5 (more than two suspicious criteria) was considered positive. The per-breast diagnostic performance of each reader was compared between the first and second reviews. Inter-reader agreement was evaluated using a multi-rater κ analysis and intraclass correlation coefficient (ICC)., Results: Before training, the mean sensitivity, specificity, and accuracy of the 16 readers were 70.7% (95% confidence interval [CI]: 59.4-79.9), 90.8% (95% CI: 85.6-94.2), and 83.5% (95% CI: 78.6-87.4), respectively. After training, significant improvements in specificity (95.2%; 95% CI: 90.8-97.5; P = 0.001) and accuracy (85.9%; 95% CI: 80.9-89.8; P = 0.01) were observed, but no difference in sensitivity (69.8%; 95% CI: 58.1-79.4; P = 0.58) was observed. Regarding inter-reader agreement, the κ values were 0.57 (95% CI: 0.52-0.63) before training and 0.68 (95% CI: 0.62-0.74) after training, with a difference of 0.11 (95% CI: 0.02-0.18; P = 0.01). The ICC was 0.73 (95% CI: 0.69-0.74) before training and 0.79 (95% CI: 0.76-0.80) after training ( P = 0.002)., Conclusion: Brief reader training improved the performance and agreement of interpretations by breast radiologists using unenhanced MRI with DWI., Competing Interests: Vivian Youngjean Park and Woo Jung Choi, the editor board member of the Korean Journal of Radiology, were not involved in the editorial evaluation or decision to publish this article. All authors have declared no conflicts of interest., (Copyright © 2023 The Korean Society of Radiology.)

Screening mammography programs have been implemented in numerous Western countries with the aim of reducing breast cancer mortality. However, despite over 20 years of population-based screening mammography, the mortality rates in Japan and Korea continue to rise. This may be due to the fact that screening mammography is not as effective for Japanese and Korean women, who often have dense breasts. This density decreases the sensitivity of mammography due to a masking effect. Therefore, the early detection of small invasive cancers requires more than just mammography, particularly for women in their 40s. This review discusses the limitations and challenges of screening mammography, as well as the keys to successful population-based breast cancer screening in Japan and Korea. This includes a focus on breast ultrasonography techniques, which are based on histopathologic anatomical knowledge, and personalized screening strategies that are based on risk assessments measured by glandular tissue components.

Purpose: To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers., Methods: In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test., Results: A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts., Conclusion: Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Detection of multifocal, multicentric, and contralateral breast cancers in patients affects surgical management. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can identify additional foci that were initially undetected by conventional imaging. However, its use is limited owing to low specificity and high false-positive rate. Multiparametric MRI (DCE-MRI + diffusion-weighted [DW] MRI) can increase the specificity. We aimed to describe the protocols of our prospective, multicenter, observational cohort studies designed to compare the diagnostic performance of DCE-MRI and multiparametric MRI for the diagnosis of multifocal, multicentric cancer and contralateral breast cancer in patients with newly diagnosed breast cancer., Methods: Two studies comparing the performance of DCE-MRI and multiparametric MRI for the diagnosis of multifocal, multicentric cancer (NCT04656639) and contralateral breast cancer (NCT05307757) will be conducted. For trial NCT04656639, 580 females with invasive breast cancer candidates for breast conservation surgery whose DCE-MRI showed additional suspicious lesions (breast imaging reporting and data system [BI-RADS] category ≥ 4) on DCE-MRI in the ipsilateral breast will be enrolled. For trial NCT05307757, 1098 females with invasive breast cancer whose DCE-MRI showed contralateral lesions (BI-RADS category ≥ 3 or higher on DCE-MRI) will be enrolled. Participants will undergo 3.0-T DCE-MRI and DW-MRI. The diagnostic performance of DCE-MRI and multiparametric MRI will be compared. The receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and characteristics of the detected cancers will be analyzed. The primary outcome is the difference in the receiver operating characteristic curve between DCE-MRI and multiparametric MRI interpretation. Enrollment completion is expected in 2024, and study results are expected to be presented in 2026., Discussion: This prospective, multicenter study will compare the performance of DCE-MRI versus multiparametric MRI for the preoperative evaluation of multifocal, multicentric, and contralateral breast cancer and is currently in the patient enrollment phase., Trial Registration: ClinicalTrials.gov Identifier: NCT04656639, NCT05307757. Registered on April 1 2022., Competing Interests: The authors declare that they have no competing interests., (© 2023 Korean Breast Cancer Society.)

Background The wide variability of screening imaging use in patients with a personal history of breast cancer (PHBC) warrants investigation of its comparative clinical effectiveness. While more intensive screening with US or MRI at an interval of less than 1 year could increase early-stage breast cancer detection, its benefit has not been established. Purpose To investigate the outcomes of semiannual multimodality screening in patients with PHBC. Materials and Methods An academic medical center database was retrospectively searched for patients diagnosed with breast cancer between January 2015 and June 2018 who had undergone annual mammography with either semiannual incidence US or MRI screening from July 2019 to December 2019 and three subsequent semiannual screenings over a 2-year period. The primary outcome was second breast cancers diagnosed during follow-up. Examination-level cancer detection and interval cancer rates were calculated. Screening performances were compared with χ 2 or Fisher exact tests or a logistic model with generalized estimating equations. Results Our final cohort included 2758 asymptomatic women (median age, 53 years; range, 20-84 years). Among 5615 US and 1807 MRI examinations, 18 breast cancers were detected after negative findings on a prior semiannual incidence US screening examination; 44% (eight of 18) were stage 0 (three detected with MRI; five, with US), and 39% (seven of 18) were stage I (three detected with MRI; four, with US). MRI had a cancer detection rate up to 17.1 per 1000 examinations (eight of 467; 95% CI: 8.7, 33.4), and the overall cancer detection rates of US and MRI were 1.8 (10 of 5615; 95% CI: 1.0, 3.3) and 4.4 (eight of 1807; 95% CI: 2.2, 8.8) per 1000 examinations, respectively ( P = .11). Conclusion Supplemental semiannual US or MRI screening depicted second breast cancers after negative findings at prior semiannual incidence US examination in patients with PHBC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Berg in this issue.

Objective: To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts., Materials and Methods: A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared., Results: A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40-78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8-19.7] vs. 9.8 [17 of 1726; 95% CI: 5.7-15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%-34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%-24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%-28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%-18.9%; P < 0.001)., Conclusion: DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2023 The Korean Society of Radiology.)

Breast density is an independent risk factor for breast cancer. In digital mammography and digital breast tomosynthesis, breast density is assessed visually using the four-category scale developed by the American College of Radiology Breast Imaging Reporting and Data System (5th edition as of November 2022). Epidemiologically based risk models, such as the Tyrer-Cuzick model (version 8), demonstrate superior modeling performance when mammographic density is incorporated. Beyond just density, a separate mammographic measure of breast cancer risk is parenchymal textural complexity. With advancements in radiomics and deep learning, mammographic textural patterns can be assessed quantitatively and incorporated into risk models. Other supplemental screening modalities, such as breast US and MRI, offer independent risk measures complementary to those derived from mammography. Breast US allows the two components of fibroglandular tissue (stromal and glandular) to be visualized separately in a manner that is not possible with mammography. A higher glandular component at screening breast US is associated with higher risk. With MRI, a higher background parenchymal enhancement of the fibroglandular tissue has also emerged as an imaging marker for risk assessment. Imaging markers observed at mammography, US, and MRI are powerful tools in refining breast cancer risk prediction, beyond mammographic density alone., (© RSNA, 2023.)

Background Background parenchymal enhancement (BPE) is a known risk factor for breast cancer. However, studies on the association between BPE and second breast cancer risk are still lacking. Purpose To investigate whether BPE at surveillance breast MRI is associated with subsequent second breast cancer risk in women with a personal history of breast cancer. Materials and Methods A retrospective search of the imaging database of an academic medical center identified consecutive surveillance breast MRI examinations performed between January 2008 and December 2017 in women who underwent surgery for primary breast cancer and had no prior diagnosis of second breast cancer. BPE at surveillance breast MRI was qualitatively assessed using a four-category classification of minimal, mild, moderate, or marked. Future second breast cancer was defined as ipsilateral breast tumor recurrence or contralateral breast cancer diagnosed at least 1 year after each surveillance breast MRI examination. Factors associated with future second breast cancer risk were evaluated using the multivariable Fine-Gray subdistribution hazard model. Results Among the 2668 women (mean age at baseline surveillance breast MRI, 49 years ± 8 [SD]), 109 developed a second breast cancer (49 ipsilateral, 58 contralateral, and two ipsilateral and contralateral) at a median follow-up of 5.8 years. Mild, moderate, or marked BPE at surveillance breast MRI (hazard ratio [HR], 2.1 [95% CI: 1.4, 3.1]; P < .001), young age (<45 years) at initial breast cancer diagnosis (HR, 3.4 [95% CI: 1.7, 6.4]; P < .001), positive results from a BRCA1/2 genetic test (HR, 6.5 [95% CI: 3.5, 12.0]; P < .001), and negative hormone receptor expression in the initial breast cancer (HR, 1.6 [95% CI: 1.1, 2.6]; P = .02) were independently associated with an increased risk of future second breast cancer. Conclusion Background parenchymal enhancement at surveillance breast MRI was associated with future second breast cancer risk in women with a personal history of breast cancer. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Niell in this issue.

Objective: To conduct a simulation study to determine whether artificial intelligence (AI)-aided mammography reading can reduce unnecessary recalls while maintaining cancer detection ability in women recalled after mammography screening., Materials and Methods: A retrospective reader study was performed by screening mammographies of 793 women (mean age ± standard deviation, 50 ± 9 years) recalled to obtain supplemental mammographic views regarding screening mammography-detected abnormalities between January 2016 and December 2019 at two screening centers. Initial screening mammography examinations were interpreted by three dedicated breast radiologists sequentially, case by case, with and without AI aid, in a single session. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and recall rate for breast cancer diagnosis were obtained and compared between the two reading modes., Results: Fifty-four mammograms with cancer (35 invasive cancers and 19 ductal carcinomas in situ) and 739 mammograms with benign or negative findings were included. The reader-averaged AUC improved after AI aid, from 0.79 (95% confidence interval [CI], 0.74-0.85) to 0.89 (95% CI, 0.85-0.94) ( p < 0.001). The reader-averaged specificities before and after AI aid were 41.9% (95% CI, 39.3%-44.5%) and 53.9% (95% CI, 50.9%-56.9%), respectively ( p < 0.001). The reader-averaged sensitivity was not statistically different between AI-unaided and AI-aided readings: 89.5% (95% CI, 83.1%-95.9%) vs. 92.6% (95% CI, 86.2%-99.0%) ( p = 0.053), although the sensitivities of the least experienced radiologists before and after AI aid were 79.6% (43 of 54 [95% CI, 66.5%-89.4%]) and 90.7% (49 of 54 [95% CI, 79.7%-96.9%]), respectively ( p = 0.031). With AI aid, the reader-averaged recall rate decreased by from 60.4% (95% CI, 57.8%-62.9%) to 49.5% (95% CI, 46.5%-52.4%) ( p < 0.001)., Conclusion: AI-aided reading reduced the number of recalls and improved the diagnostic performance in our simulation using women initially recalled for supplemental mammographic views after mammography screening., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Korean Society of Radiology.)

Background Accurate preoperative prediction of upstaging in women with biopsy-proven ductal carcinoma in situ (DCIS) is important for surgical planning, but published models using predictive MRI features remain lacking. Purpose To develop and validate a predictive model based on preoperative breast MRI to predict upstaging in women with biopsy-proven DCIS and to select high-risk women who may benefit from sentinel lymph node biopsy at initial surgery. Materials and methods Consecutive women with biopsy-proven DCIS who underwent preoperative 3.0-T breast MRI including dynamic contrast-enhanced (DCE) MRI and diffusion-weighted imaging (DWI) and who underwent surgery between June 2019 and March 2020 were retrospectively identified (development set) from an academic medical center. The apparent diffusion coefficients of lesions from DWI, lesion size and morphologic features on DCE MRI scans, mammographic findings, age, symptoms, biopsy method, and DCIS grade at biopsy were collected. The presence of invasive cancer and axillary metastases was determined with surgical pathology. A predictive model for upstaging was developed by using multivariable logistic regression and validated in a subsequent prospective internal validation set recruited between July 2020 and April 2021. Results Fifty-seven (41%) of 140 women (mean age, 53 years ± 11 [SD]) in the development set and 43 (41%) of 105 women (mean age, 53 years ± 10) in the validation set were upstaged after surgery. The predictive model combining DWI and clinical-pathologic factors showed the areas under the receiver operating characteristic curve at 0.87 (95% CI: 0.80, 0.92) in the development set and 0.76 (95% CI: 0.67, 0.84) in the validation set. The predicted probability of invasive cancer showed good interobserver agreement (intraclass correlation coefficient, 0.79); the positive predictive value was 85% (28 of 33), and the negative predictive value was 92% (22 of 24). Conclusion A predictive model based on diffusion-weighted breast MRI identified women at high risk of upstaging. © RSNA, 2022 Online supplemental material is available for this article See also the editorial by Baltzer in this issue. An earlier incorrect version appeared online. This article was corrected on July 7, 2022.

Background Both temporal changes in imaging characteristics of lymphadenopathy on US scans after COVID-19 vaccination and expected duration of radiologically evident lymphadenopathy remain uncertain. Purpose To longitudinally evaluate COVID-19 vaccine-associated lymphadenopathy on axillary US scans at various time intervals in both messenger (mRNA) and vector vaccine recipients. Materials and Methods This prospective cohort study was conducted between March 2021 and January 2022. The participants were asymptomatic women without breast cancer who had received COVID-19 vaccination. Serial follow-up US was performed in women with lymphadenopathy. The following variables were assessed: cortical thickness, number of lymph nodes, morphologic characteristics, and Doppler signal. Temporal changes in cortical thickness and number of lymph nodes during follow-up were assessed using a linear mixed model. Results Ninety-one women with lymphadenopathy in the vaccinated arm had undergone a total of 215 serial US examinations (mean age, 44 years ± 13 [SD]). Fifty-one participants had received a vector vaccine (ChAdOx1 nCoV-19 vaccine) and 40 had received an mRNA vaccine (BNT162b2 vaccine [ n = 37] and mRNA-1273 vaccine [ n = 3]). Three of the 91 women were lost to follow-up; thus, 88 women underwent serial US. Complete resolution of axillary lymphadenopathy was observed at a median of 6 weeks after vaccination (range, 4-7 weeks) in 26% of women (23 of 88). Among 49 women with follow-up US at a median of 12 weeks after vaccination (range, 8-14 weeks), persistent lymphadenopathy was observed in 25 (51%). During the follow-up period, the cortical thickness gradually decreased ( P < .001) over time regardless of vaccine type; however, values were higher in recipients of the mRNA vaccine than in recipients of the vector vaccine ( P = .02). Conclusion COVID-19 vaccine-associated axillary lymphadenopathy frequently persisted for more than 6 weeks on US scans. Lymphadenopathy should be interpreted considering vaccine type and time elapsed since vaccination. Follow-up US examination at least 12 weeks after vaccination may be reasonable, particularly for recipients of the messenger RNA vaccine. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Moy and Kim in this issue.

Background Few studies have compared abbreviated breast MRI with full-protocol MRI in women with a personal history of breast cancer (PHBC), and they have not adjusted for confounding variables. Purpose To compare abbreviated breast MRI with full-protocol MRI in women with PHBC by using propensity score matching to adjust for confounding variables. Materials and Methods In this single-center retrospective study, women with PHBC who underwent full-protocol MRI (January 2008-August 2017) or abbreviated MRI (September 2017-April 2019) were identified. With use of a propensity score-matched cohort, screening performances were compared between the two MRI groups with the McNemar test or a propensity score-adjusted generalized estimating equation. The coprimary analyses were sensitivity and specificity. The secondary analyses were the cancer detection rate, interval cancer rate, positive predictive value for biopsies performed (PPV3), and Breast Imaging Reporting and Data System (BI-RADS) category 3 short-term follow-up rate. Results There were 726 women allocated to each MRI group (mean age ± SD, 50 years ± 8 for both groups). Abbreviated MRI and full-protocol MRI showed comparable sensitivity (15 of 15 cancers [100%; 95% CI: 78, 100] vs nine of 13 cancers [69%; 95% CI: 39, 91], respectively; P = .17). Abbreviated MRI showed higher specificity than full-protocol MRI (660 of 711 examinations [93%; 95% CI: 91, 95] vs 612 of 713 examinations [86%; 95% CI: 83, 88], respectively; P < .001). The cancer detection rate (21 vs 12 per 1000 examinations), interval cancer rate (0 vs five per 1000 examinations), and PPV3 (61% [14 of 23 examinations] vs 41% [nine of 22 examinations]) were comparable (all P < .05). The BI-RADS category 3 short-term follow-up rate of abbreviated MRI was less than half that of full-protocol MRI (5% [36 of 726 examinations] vs 12% [84 of 726 examinations], respectively; P < .001). Ninety-three percent (14 of 15) of cancers detected at abbreviated MRI were node-negative T1-invasive cancers ( n = 6) or ductal carcinoma in situ ( n = 8). Conclusion Abbreviated breast MRI showed comparable sensitivity and superior specificity to full-protocol MRI in breast cancer detection in women with a personal history of breast cancer. © RSNA, 2022 Online supplemental material is available for this article .

Objective: The optimal imaging approach for evaluating pathological nipple discharge remains unclear. We investigated the value of adding ductography to ultrasound (US) for evaluating pathologic nipple discharge in patients with negative mammography findings., Materials and Methods: From July 2003 to December 2018, 101 women (mean age, 46.3 ± 12.2 years; range, 23-75 years) with pathologic nipple discharge were evaluated using pre-ductography (initial) US, ductography, and post-ductography US. The imaging findings were reviewed retrospectively. The standard reference was surgery (70 patients) or > 2 years of follow-up with US (31 patients). The diagnostic performances of initial US, ductography, and post-ductography US for detecting malignancy were compared using the McNemar's test or a generalized estimating equation., Results: In total, 47 papillomas, 30 other benign lesions, seven high-risk lesions, and 17 malignant lesions were identified as underlying causes of pathologic nipple discharge. Only eight of the 17 malignancies were detected on the initial US, while the remaining nine malignancies were detected by ductography. Among the nine malignancies detected by ductography, eight were detected on post-ductography US and could be localized for US-guided intervention. The sensitivities of ductography (94.1% [16/17]) and post-ductography US (94.1% [16/17]) were significantly higher than those of initial US (47.1% [8/17]; p = 0.027 and 0.013, respectively). The negative predictive value of post-ductography US (96.9% [31/32]) was significantly higher than that of the initial US (83.3% [45/54]; p = 0.006). Specificity was significantly higher for initial US than for ductography and post-ductography US ( p = 0.001 for all)., Conclusion: The combined use of ductography and US has a high sensitivity for detecting malignancy in patients with pathologic nipple discharge and negative mammography. Ductography findings enable lesion localization on second-look post-ductography US, thus facilitating the selection of optimal treatment plans., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 The Korean Society of Radiology.)

Background Little is known regarding findings at imaging associated with survival in patients with luminal breast cancer treated with neoadjuvant chemotherapy (NAC). Purpose To determine the relationship between imaging (MRI, US, and mammography) and clinical-pathologic variables in predicting distant metastasis-free survival (DMFS) and overall survival (OS) in patients with luminal breast cancer treated with NAC. Materials and Methods In this retrospective study, consecutive women with luminal breast cancer who underwent NAC followed by surgery were identified from the breast cancer registries of two hospitals. Women from one hospital between January 2003 and July 2015 were classified into the development cohort, and women from the other hospital between January 2007 and July 2015 were classified into the validation cohort. MRI scans, US scans, and mammograms before and after NAC (hereafter, referred to as pre- and post-NAC, respectively) and clinical-pathologic data were reviewed. Peritumoral edema was defined as the water-like high signal intensity surrounding the tumor on T2-weighted MRI scans. The prediction model was developed in the development cohort by using Cox regression and then tested in the validation cohort. Results The development cohort consisted of 318 women (68 distant metastases, 54 deaths) and the validation cohort consisted of 165 women (37 distant metastases, 14 deaths) (median age, 46 years in both cohorts). Post-NAC MRI peritumoral edema, age younger than 40 years, clinical N2 or N3, and lymphovascular invasion were associated with worse DMFS (all, P < .05). Pre-NAC mammographic microcalcifications, post-NAC MRI peritumoral edema, age older than 60 years, and clinical T3 or T4 were associated with worse OS (all, P < .05). The prediction model showed good discrimination ability (C index, 0.67-0.75 for DMFS and 0.70-0.77 for OS) and stratified prognosis into low-risk and high-risk groups (10-year DMFS rates, 79% vs 21%, respectively; and 10-year OS rates, 95%-96% vs 63%-67%, respectively) in the validation cohort. Conclusion MRI features and clinical-pathologic variables were identified that were associated with prolonged survival of patients with luminal breast cancer treated with neoadjuvant chemotherapy. © RSNA, 2022 Online supplemental material is available for this article . See also the editorial by Kataoka in this issue.

Background: SerpinB2 is highly expressed in immune and tumor cells and is involved in multiple biological functions, including cell survival and remodeling for disease progression. This study prepared SerpinB2-deficient mice and analyzed the differentially expressed genes (DEGs) to determine if loss of this protein delays mammary tumor progression., Results: A total of 305 DEGs (75 upregulated and 230 downregulated; > 1.5-fold difference, P < 0.05) were identified in SB2-/-;PyMT tumors compared with PyMT tumors. The DEGs were mainly involved in immune and inflammatory responses related to T cell differentiation, IFN-γ production, and lymphocyte chemotaxis based on 61 enriched GO terms, hierarchical clustering, KEGG pathways, and a functionally grouped annotation network. The significantly changed DEGs (Anxa3, Ccl17, Cxcl13, Cxcr3, IFN-γ, Nr4a1, and Sema3a) annotated with at least two GO categories in SB2-/-;PyMT tumors was validated by qRT-PCR., Conclusions: SerpinB2 deficiency alters the expression of multiple genes in mammary tumors, which might cause a delay in PyMT-induced mammary tumor progression., (© 2022. The Author(s).)

Purpose: To evaluate the added value of ultrafast MRI in abbreviated breast MRI (AB-MRI) surveillance in women with a personal history of breast cancer (PHBC)., Method: Between September 2017 and November 2019, consecutive postoperative surveillance AB-MRIs with ultrafast MRIs (20 images with a 4.0-second temporal resolution using 4D time-resolved angiography with keyhole technique) were retrospectively collected. Four blinded radiologists independently classified the Breast Imaging Reporting and Data System (BI-RADS) category for AB-MRI alone versus the combined protocol (AB-MRI + ultrafast MRI). Readers were recommended to change BI-RADS category according to the time to enhancement cut-off of 12 s in ultrafast MRI. McNemar test and generalized estimation equation model were used to compare the diagnostic performances., Results: A total of 867 MRI examinations in 867 women (mean age ± standard deviation, 51 years ± 8) were evaluated. The sensitivity of both protocols among all readers was the same, at 90% (9/10). Addition of ultrafast MRI improved the specificity (a mean of 95.3% vs. 88.6 %, p < 0.001 for all readers) and positive predictive value 1 (PPV 1 ) (a mean of 21% vs. 10%, p < 0.001 for all readers) compared to AB-MRI alone. Downgrading BI-RADS category 3 to 2 in four readers in a mean of 6.7% (57 of 857) of negative or benign findings was the main reason for the improved specificity and PPV 1 ., Conclusion: Addition of ultrafast MRI to AB-MRI improved the specificity and PPV 1 by reducing unnecessary short-term follow-ups without compromising sensitivity in postoperative surveillance., (Copyright © 2022. Published by Elsevier B.V.)

Competing Interests: The authors have no potential conflicts of interest to disclose.

This study aimed to evaluate the imaging and pathological findings in axillary lymph nodes in patients with breast cancer who received concurrent ipsilateral coronavirus disease 2019 (COVID-19) vaccination. Of the 19 women with breast cancer who received concurrent COVID-19 vaccination shot in the arm ipsilateral to breast cancer, axillary lymphadenopathy was observed in 84.2% (16 of 19) of patients on ultrasound (US) and 71.4% (10 of 14) of patients on magnetic resonance imaging (MRI), and 21.0% (4 of 19) of patients were diagnosed with metastasis. Abnormal US and MRI findings of cortical thickening, effacement of the fatty hilum, round shape, and asymmetry in the number or size relative to the contralateral side were noted in more than half of the non-metastatic and metastatic lymph nodes; however, statistical significance was not noted. Axillary lymphadenopathy is commonly observed in patients with breast cancer who receive concurrent ipsilateral COVID-19 vaccination without specific differential imaging features. Thus, understanding the limitations of axillary imaging and cautious interpretation is necessary to avoid overestimation or underestimation of the axillary disease burden., Competing Interests: The authors declare that they have no competing interests., (© 2022 Korean Breast Cancer Society.)

Background: Following sentinel lymph node biopsy (SLNB), the axillary recurrence rate is very low although SLNB has a false-negative rate of 5-10%. In the ACOSOG Z0011 trial, non-sentinel positive-lymph nodes were found in more than 20% of the axillary dissection group; the SLNB only group did not have a higher axillary recurrence rate. These findings raised questions about the direct therapeutic effect of the SLNB. SLNB has post-surgical complications including lymphedema. Considering advances in imaging modalities and adjuvant therapies, the role of SLNB in early breast cancer needs to be re-evaluated., Methods: The NAUTILUS trial is a prospective multicenter randomized controlled trial involving clinical stage T1-2 and N0 breast cancer patients receiving breast-conserving surgery. Axillary ultrasound is mandatory before surgery with predefined imaging criteria for inclusion. Ultrasound-guided core needle biopsy or needle aspiration of a suspicious node is allowed. Patients will be randomized (1:1) into the no-SLNB (test) and SLNB (control) groups. A total of 1734 patients are needed, considering a 5% non-inferiority margin, 5% significance level, 80% statistical power, and 10% dropout rate. All patients in the two groups will receive ipsilateral whole-breast radiation according to a predefined protocol. The primary endpoint of this trial is the 5-year invasive disease-free survival. The secondary endpoints are overall survival, distant metastasis-free survival, axillary recurrence rate, and quality of life of the patients., Discussion: This trial will provide important evidence on the oncological safety of the omission of SLNB for early breast cancer patients undergoing breast-conserving surgery and receiving whole-breast radiation, especially when the axillary lymph node is not suspicious during preoperative axillary ultrasound., Trial Registration: ClinicalTrials.gov, NCT04303715 . Registered on March 11, 2020., (© 2022. The Author(s).)

Purpose: To evaluate the axillary recurrence rate and usefulness of axillary ultrasound (AUS) during supplementary whole-breast ultrasound (US) screening in women with a personal history of breast cancer (PHBC)., Methods: A retrospective database search identified consecutive asymptomatic women who underwent postoperative supplemental whole-breast US screening, including that of the bilateral axillae, after negative findings on mammography between January and June 2017. Using the pathologic data or at least 1-year follow-up data as reference standards, the axillary recurrence rate, cancer detection rate (CDR), interval axillary recurrence rate per 1,000 screenings, sensitivity, specificity, and abnormal interpretation rate (AIR) were estimated., Results: From the data of 4,430 women (mean age, 55.0 ± 10.1 years) analyzed in this study, there were five axillary recurrence cases (1.1/1,000) in the median follow-up period of 57.2 months. AUS showed a CDR of 0.2 (1/4,430; 95% confidence interval [CI], 0.01-1.3) and an interval axillary recurrence rate of 0.9 (4/4,402; 95% CI, 0.2-2.3) per 1,000 examinations. The sensitivity and specificity were 20.0% (1/5; 95% CI, 0.5-71.6), and 99.4% (4,398/4,425; 95% CI, 99.1-99.6), respectively, while the AIR was 0.6% (28/4,430; 95% CI, 0.4-0.9%)., Conclusion: In asymptomatic women with a PHBC and negative findings on mammography, axillary recurrence after breast cancer and axillary treatment was uncommon, and the supplemental AUS screening yielded 0.2 cancers per 1,000 examinations., Competing Interests: The authors declare that they have no competing interests., (© 2022 Korean Breast Cancer Society.)

Axillary ultrasonography (US) is the most commonly used imaging modality for nodal evaluation in patients with breast cancer. No Axillary Surgical Treatment in Clinically Lymph Node-Negative Patients after Ultrasonography (NAUTILUS) is a prospective, multicenter, randomized controlled trial investigating whether sentinel lymph node biopsy (SLNB) can be safely omitted in patients with clinically and sonographically node-negative T1-2 breast cancer treated with breast-conserving therapy. In this trial, a standardized imaging protocol and criteria were established for the evaluation of axillary lymph nodes. Women lacking palpable lymph nodes underwent axillary US to dismiss suspicious nodal involvement. Patients with a round hypoechoic node with effaced hilum or indistinct margins were excluded. Patients with T1 tumors and a single node with a cortical thickness ≥ 3 mm underwent US-guided biopsy. Finally, patients with negative axillary US findings were included. The NAUTILUS axillary US nodal assessment criteria facilitate the proper selection of candidates who can omit SLNB. Trial Registration: ClinicalTrials.gov Identifier: NCT04303715., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

Purpose: The breast cancer susceptibility gene, BRCA1 , is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in BRCA1 mutant mice., Methods: Five BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 BRCA1 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired t -test., Results: One-month-old BRCA1 mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, p = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, p = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, p = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In BRCA1 mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, p = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, p = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, p = 0.8099) between the groups., Conclusion: BRCA1 mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for BRCA1 mutation carriers., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with tumor progression in breast cancer. Although crosstalk between breast cancer cells and CAFs has been studied, the effect of CAFs on non-neoplastic breast epithelial cells is not fully understood to date. Here, we investigated the effect of CAFs on aggressive phenotypes in non-neoplastic MCF10A breast epithelial cells. CAFs induced epithelial-to-mesenchymal transition (EMT) and invasive phenotype in MCF10A cells. S100A8, a potential prognostic marker in several cancers, was markedly increased in MCF10A cells by CAFs. S100A8 was crucial for CAFs-induced invasive phenotype of MCF10A cells. Among cytokines increased by CAFs, interleukin (IL)-8 induced S100A8 through transcription factors p65 NF-κB and C/EBPβ. In a xenograft mouse model with MCF10A cells and CAFs, tumor was not developed, suggesting that coinjection with CAFs may not be sufficient for in vivo tumorigenicity of MCF10A cells. Xenograft mouse tumor models with MDA-MB-231 breast carcinoma cells provided an in vivo evidence for the effect of CAFs on breast cancer progression as well as a crucial role of IL-8 in tumor growth and S100A8 expression in vivo. Using a tissue microarray of human breast cancer, we showed that S100A8 expression was correlated with poor outcomes. S100A8 expression was more frequently detected in cancer-adjacent normal human breast tissues than in normal breast tissues. Together, this study elucidated a novel mechanism for the acquisition of invasive phenotype of non-neoplastic breast cells induced by CAFs, suggesting that targeting IL-8 and S100A8 may be an effective strategy against breast cancer., (© 2021 Wiley Periodicals LLC.)

Background Breast density at mammography is an established risk factor for breast cancer, but it cannot be used to distinguish between glandular and fibrous tissue. Purpose To evaluate the association between the glandular tissue component (GTC) at screening breast US and the risk of future breast cancer in women with dense breasts and the association between the GTC and lobular involution. Materials and Methods Screening breast US examinations performed in women with no prior history of breast cancer and with dense breasts with negative findings from mammography from January 2012 to December 2015 were retrospectively identified. The GTC was reported as being minimal, mild, moderate, or marked at the time of the US examination. In women who had benign breast biopsy results, the degree of lobular involution in normal background tissue was categorized as not present, mild, moderate, or complete. The GTC-related breast cancer risk in women with a cancer diagnosis or follow-up after 6 months was estimated by using Cox proportional hazards regression. Cumulative logistic regression was used to evaluate the association between the GTC and lobular involution. Results Among 8483 women (mean age, 49 years ± 8 [standard deviation]), 137 developed breast cancer over a median follow-up time of 5.3 years. Compared with a minimal or mild GTC, a moderate or marked GTC was associated with an increased cancer risk (hazard ratio, 1.5; 95% CI: 1.05, 2.1; P = .03) after adjusting for age and breast density. The GTC had an inverse association with lobular involution; women with no, mild, or moderate involution had greater odds (odds ratios of 4.9 [95% CI: 1.5, 16.6], 2.6 [95% CI: 0.95, 7.2], and 1.8 [95% CI: 0.7, 4.6], respectively) of a moderate or marked GTC than those with complete involution ( P = .004). Conclusion The glandular tissue component was independently associated with the future breast cancer risk in women with dense breasts and reflects the lobular involution. It should be considered for risk stratification during screening breast US. © RSNA, 2021 Online supplemental material is available for this article.

Objectives: To prospectively evaluate the diagnostic performance of screening ABUS as the primary screening test for breast cancer among Korean women aged 40-49 years., Methods: This prospective, multicenter study included asymptomatic Korean women aged 40-49 years from three academic centers between February 2017 and October 2019. Each participant underwent ABUS without mammography, and the ABUS images were interpreted at each hospital with double-reading by two breast radiologists. Biopsy and at least 1 year of follow-up was considered the reference standard. Diagnostic performance of ABUS screening and subgroup analyses according to patient and tumor characteristics were evaluated., Results: Reference standard data were available for 959 women. The recall rate was 9.8% (95% confidence interval [CI]: 7.9%, 11.7%; 94 of 959 women) and the cancer detection yield was 5.2 per 1000 women (95% CI: -0.6, 11.1; 5 of 959 women). There was only one interval cancer. The sensitivity was 83.3% (95% CI: 53.5%, 100%; 5 of 6 cancers) and the specificity was 90.7% (95% CI: 88.8%, 92.5%; 864 of 95. women). The positive predictive values of biopsies performed (PPV 3 ) was 20.0% (95% CI: 4.3%, 35.7%; 5 of 25 women). Women with heterogeneous background echotexture had a higher recall rate (p = .009) and lower specificity (p = .036). Women with body mass index values < 25 kg/m 2 had a higher mean recall rate (p = .046)., Conclusion: In East Asia, screening automated breast US may be an alternative to screening mammography for detecting breast cancers in women aged 40-49 years., Key Points: • Automated breast US screening for breast cancer in asymptomatic women aged 40-49 is effective with 5.2 per 1000 cancer detection yield. • Women with heterogeneous background echotexture had a higher recall rate and lower specificity. • Women with body mass index < 25 kg/m 2 had a higher recall rate., (© 2021. European Society of Radiology.)

We here evaluated the therapeutic effect of tumor cell-derived exosomes (TEXs)-stimulated dendritic cells (DCs) in a syngeneic orthotopic breast tumor model. The DC line DC2.4 and breast cancer cell line E0771 originally isolated from C57BL/6 mice were used. E0771 cells stably expressing the exosomal CD63-RFP or luciferase (Luc) and DC2.4 cells stably expressing GFP were produced using lentivirus. TEXs were purified from conditioned medium of E0771/CD63-RFP cells. Breast tumor model was established by injecting E0771/Luc cells into mammary gland fat pad of mice. TEXs contained immune modulatory molecules such as HSP70, HSP90, MHC I, MHC II, TGF-β, and PD-L1. TEXs were easily taken by DC2.4 cells, resulting in a significant increase in the in vitro proliferation and migration abilities of DC2.4 cells, accompanied by the upregulation of CD40. TEX-DC-treated group exhibited a decreased tumor growth compared with control group. CD8 + cells were more abundant in the tumors and lymph nodes of TEX-DC-treated group than in those of control group, whereas many CD4 + or FOXP3+ cells were localized in those of control group. Our results suggest a potential application of TEX-DC-based cancer immunotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background There are few interval cancer studies of incident screening MRI for women with a personal history of breast cancer (PHBC). Purpose To evaluate the performance measures of screening breast MRI in women with a PHBC across multiple rounds and to identify subgroups who might be more at risk for interval cancer. Materials and Methods Between January 2008 and March 2019, consecutive screening breast MRI studies for women who had undergone breast-conserving surgery because of breast cancer were retrospectively identified. Inclusion criteria were negative or benign findings at mammography with US, availability of at least 1 year of follow-up data, and examinations having been performed within 12 months after the initial cancer surgery. Performance measures were calculated for each round. Multivariable logistic regression analysis was performed to determine factors associated with the risk of interval cancer. Results Among the 6603 MRI examinations for 2809 women (median age, 47 years; interquartile range, 42-53 years), the cancer detection rate was 8.3 per 1000 screening examinations (55 of 6603 examinations) and the interval cancer rate was 1.5 per 1000 screening examinations (10 of 6603 examinations). The sensitivity and specificity were 85% (55 of 65 examinations; 95% CI: 76, 93) and 88.3% (5775 of 6538 examinations; 95% CI: 87.6, 89.1), respectively. At multivariable analysis, interval cancers were associated with a first-degree family history of breast cancer (odds ratio [OR], 5.4; 95% CI: 1.3, 22.5; P = .02), estrogen receptor- and progesterone receptor-negative primary cancers (OR, 3.6; 95% CI: 1.1, 12.2; P = .04), and moderate or marked background parenchymal enhancement (OR, 10.8; 95% CI: 3.3, 35.7; P < .001). Conclusion Performance of screening breast MRI in women with a personal history of breast cancer was sustained across multiple rounds, and a first-degree family history of breast cancer, estrogen receptor- and progesterone receptor-negative primary cancers, and moderate or marked background parenchymal enhancement at MRI were independently associated with the risk of developing interval cancers. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Slanetz in this issue.

Background: There is increasing interest in noncontrast-enhanced MRI due to safety concerns for gadolinium contrast agents., Purpose: To investigate the clinical feasibility of MR-based conductivity imaging for breast cancer detection and lesion differentiation., Study Type: Prospective., Subjects: One hundred and ten women, with 112 known cancers and 17 benign lesions (biopsy-proven), scheduled for preoperative MRI., Field Strength/sequence: Non-fat-suppressed T2-weighted turbo spin-echo sequence (T2WI), dynamic contrast-enhanced MRI and diffusion-weighted imaging (DWI) at 3T., Assessment: Cancer detectability on each imaging modality was qualitatively evaluated on a per-breast basis: the conductivity maps derived from T2WI were independently reviewed by three radiologists (R1-R3). T2WI, DWI, and pre-operative digital mammography were independently reviewed by three other radiologists (R4-R6). Conductivity and apparent diffusion coefficient (ADC) measurements (mean, minimum, and maximum) were performed for 112 cancers and 17 benign lesions independently by two radiologists (R1 and R2). Tumor size was measured from surgical specimens., Statistical Tests: Cancer detection rates were compared using generalized estimating equations. Multivariable logistic regression analysis was performed to identify factors associated with cancer detectability. Discriminating ability of conductivity and ADC was evaluated by using the areas under the receiver operating characteristic curve (AUC)., Results: Conductivity imaging showed lower cancer detection rates (20%-32%) compared to T2WI (62%-71%), DWI (85%-90%), and mammography (79%-88%) (all P < 0.05). Fatty breast on MRI (odds ratio = 11.8, P < 0.05) and invasive tumor size (odds ratio = 1.7, P < 0.05) were associated with cancer detectability of conductivity imaging. The maximum conductivity showed comparable ability to the mean ADC in discriminating between cancers and benign lesions (AUC = 0.67 [95% CI: 0.59, 0.75] vs. 0.84 [0.76, 0.90], P = 0.06 (R1); 0.65 [0.56, 0.73] vs. 0.82 [0.74, 0.88], P = 0.07 (R2))., Data Conclusion: Although conductivity imaging showed suboptimal performance in breast cancer detection, the quantitative measurement of conductivity showed the potential for lesion differentiation., Evidence Level: 1 TECHNICAL EFFICACY: Stage 2., (© 2021 International Society for Magnetic Resonance in Medicine.)

Objective: To compare the screening performance of diffusion-weighted (DW) MRI and combined mammography and ultrasound (US) in detecting clinically occult contralateral breast cancer in women with newly diagnosed breast cancer., Materials and Methods: Between January 2017 and July 2018, 1148 women (mean age ± standard deviation, 53.2 ± 10.8 years) with unilateral breast cancer and no clinical abnormalities in the contralateral breast underwent 3T MRI, digital mammography, and radiologist-performed whole-breast US. In this retrospective study, three radiologists independently and blindly reviewed all DW MR images (b = 1000 s/mm² and apparent diffusion coefficient map) of the contralateral breast and assigned a Breast Imaging Reporting and Data System category. For combined mammography and US evaluation, prospectively assessed results were used. Using histopathology or 1-year follow-up as the reference standard, cancer detection rate and the patient percentage with cancers detected among all women recommended for tissue diagnosis (positive predictive value; PPV₂) were compared., Results: Of the 30 cases of clinically occult contralateral cancers (13 invasive and 17 ductal carcinoma in situ [DCIS]), DW MRI detected 23 (76.7%) cases (11 invasive and 12 DCIS), whereas combined mammography and US detected 12 (40.0%, five invasive and seven DCIS) cases. All cancers detected by combined mammography and US, except two DCIS cases, were detected by DW MRI. The cancer detection rate of DW MRI (2.0%; 95% confidence interval [CI]: 1.3%, 3.0%) was higher than that of combined mammography and US (1.0%; 95% CI: 0.5%, 1.8%; p = 0.009). DW MRI showed higher PPV₂ (42.1%; 95% CI: 26.3%, 59.2%) than combined mammography and US (18.5%; 95% CI: 9.9%, 30.0%; p = 0.001)., Conclusion: In women with newly diagnosed breast cancer, DW MRI detected significantly more contralateral breast cancers with fewer biopsy recommendations than combined mammography and US., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Background There is an increasing need to develop a more accurate prediction model for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer. Purpose To develop a nomogram based on MRI and clinical-pathologic variables to predict pCR. Materials and Methods In this single-center retrospective study, consecutive women with stage II-III breast cancer who underwent NAC followed by surgery between January 2011 and December 2017 were considered for inclusion. The women were divided into a development cohort between January 2011 and September 2015 and a validation cohort between October 2015 and December 2017. Clinical-pathologic data were collected, and mammograms and MRI scans obtained before and after NAC were analyzed. Logistic regression analyses were performed to identify independent variables associated with pCR in the development cohort from which the nomogram was created. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration slope. Results A total of 359 women (mean age, 49 years ± 10 [standard deviation]) were in the development cohort and 351 (49 years ± 10) in the validation cohort. Hormone receptor negativity (odds ratio [OR], 3.1; 95% CI: 1.4, 7.1; P = .006), high Ki-67 index (OR, 1.05; 95% CI: 1.03, 1.07; P < .001), and post-NAC MRI variables, including small tumor size (OR, 0.6; 95% CI: 0.4, 0.9; P = .03), low lesion-to-background parenchymal signal enhancement ratio (OR, 0.2; 95% CI: 0.1, 0.6; P = .004), and absence of enhancement in the tumor bed (OR, 3.8; 95% CI: 1.4, 10.5; P = .009) were independently associated with pCR. The nomogram incorporating these variables showed good discrimination (AUC, 0.90; 95% CI: 0.86, 0.94) and calibration abilities (calibration slope, 0.91; 95% CI: 0.69, 1.13) in the independent validation cohort. Conclusion A nomogram incorporating hormone receptor status, Ki-67 index, and MRI variables showed good discrimination and calibration abilities in predicting pathologic complete response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Imbriaco and Ponsiglione in this issue.

Purpose: Interest in unenhanced magnetic resonance imaging (MRI) screening for breast cancer is growing due to concerns about gadolinium deposition in the brain and the high cost of contrast-enhanced MRI. The purpose of this report is to describe the protocol of the Diffusion-Weighted Magnetic Resonance Imaging Screening Trial (DWIST), which is a prospective, multicenter, intraindividual comparative cohort study designed to compare the performance of mammography, ultrasonography, dynamic contrast-enhanced (DCE) MRI, and diffusion-weighted (DW) MRI screening in women at high risk of developing breast cancer., Methods: A total of 890 women with BRCA mutation or family history of breast cancer and lifetime risk ≥ 20% are enrolled. The participants undergo 2 annual breast screenings with digital mammography, ultrasonography, DCE MRI, and DW MRI at 3.0 T. Images are independently interpreted by trained radiologists. The reference standard is a combination of pathology and 12-month follow-up. Each image modality and their combination will be compared in terms of sensitivity, specificity, accuracy, positive predictive value, rate of invasive cancer detection, abnormal interpretation rate, and characteristics of detected cancers. The first participant was enrolled in April 2019. At the time of manuscript submission, 5 academic medical centers in South Korea are actively enrolling eligible women and a total of 235 women have undergone the first round of screening. Completion of enrollment is expected in 2022 and the results of the study are expected to be published in 2026., Discussion: DWIST is the first prospective multicenter study to compare the performance of DW MRI and conventional imaging modalities for breast cancer screening in high-risk women. DWIST is currently in the patient enrollment phase., Trial Registration: ClinicalTrials.gov Identifier: NCT03835897., Competing Interests: The authors declare that they have no competing interests., (© 2021 Korean Breast Cancer Society.)

Purpose: To investigate clinical and imaging features associated with a high nodal burden (≥ 3 metastatic lymph nodes [LNs]) and compare diagnostic performance of US and MRI in patients with invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC)., Methods: Retrospective search revealed 239 patients with ILC and 999 with IDC who underwent preoperative US and MRI between January 2016 and June 2019. Patients with ILC were propensity-score-matched with patients with IDC. Univariate and multivariate logistic regression analyses were performed to determine factors associated with ≥ 3 metastatic LNs., Results: 412 patients (206 ILC and 206 IDC) were evaluated. Of all patients with ILC, 27.2% (56/206) were node-positive and 7.8% (16/206) showed a high nodal burden. In multivariate analysis, the clinical N stage was the only independent factor associated with a high nodal burden in patients with IDC (odds ratio [OR] 6.24; 95% confidence interval [CI] 1.57-24.73; P = 0.009), but not in patients with ILC. Increased cortical thickness with loss of fatty hilum on US was associated with a high nodal burden in patients with ILC (OR 58.40; 95% CI 5.09-669.71; P = 0.001) and IDC (OR 24.14; 95% CI 3.52-165.37; P = 0.001), while suspicious LN findings at MRI were independently associated with a high nodal burden in ILC only (OR 13.94; 95% CI 2.61-74.39; P = 0.002)., Conclusion: In patients with ILC, MRI findings of suspicious LNs were helpful to predict a high nodal disease burden.

Background: In diffusion-weighted imaging (DWI) of breast MRI, simultaneous multislice acceleration techniques can be used for readout-segmented echo planar imaging (rs-EPI) to shorten the scan time., Purpose: To compare the image quality, apparent diffusion coefficient (ADC) value, and scan time of rs-EPI and simultaneous multislice rs-EPI (SMS rs-EPI) sequences., Study Type: Retrospective., Subjects: In all, 134 consecutive women (mean age: 55.3 years) with invasive breast cancer who underwent preoperative MRI., Field Strength/ Sequences: 3.0T; rs-EPI sequence, prototypic SMS rs-EPI sequence and dynamic contrast-enhanced MRI (DCE-MRI) sequence ASSESSMENT: For quantitative comparison, two radiologists independently measured the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), lesion contrast, and apparent diffusion coefficient (ADC). For qualitative comparison, image quality, lesion conspicuity, and reader preference were assessed with a reference of DCE-MRI., Statistical Tests: Paired t-tests and Mann-Whitney tests were used., Results: For SNR and CNR, there were no differences between the sequences (P = 0.342 and 0.665 for reader 1; P = 0.606 and P = 0.116 for reader 2). Lesion contrast of SMS rs-EPI was higher than that of rs-EPI (P < 0.05 for both reader 1 and reader 2). Mean tumor ADC was similar in rs-EPI and SMS rs-EPI sequences (0.98 ± 0.22 vs. 1.00 ± 0.22; P = 0.291 for reader 1, 0.98 ± 0.21 vs. 1.00 ± 0.22; P = 0.418 for reader 2). Regarding qualitative comparison, image quality and lesion conspicuity were higher in SMS rs-EPI than in rs-EPI (both P < 0.05 for both readers). The two readers regarded SMS rs-EPI as superior or equal to rs-EPI in over 90% of cases. The acquisition time was 4:30 minutes for rs-EPI and 2:31 minutes for SMS rs-EPI., Data Conclusion: The SMS rs-EPI sequence resulted in a similar ADC value and better image quality than the rs-EPI sequence in a 44.1% reduced scan time., Level of Evidence: 4 TECHNICAL EFFICACY: 3., (© 2020 International Society for Magnetic Resonance in Medicine.)

Objective: To compare the performance of simulated abbreviated breast MRI (AB-MRI) and full diagnostic (FD)-MRI in distinguishing between benign and malignant lesions detected by MRI and investigate the features of discrepant lesions of the two protocols., Materials and Methods: An AB-MRI set with single first postcontrast images was retrospectively obtained from an FD-MRI cohort of 111 lesions (34 malignant, 77 benign) detected by contralateral breast MRI in 111 women (mean age, 49.8. ± 9.8; range, 28-75 years) with recently diagnosed breast cancer. Five blinded readers independently classified the likelihood of malignancy using Breast Imaging Reporting and Data System assessments. McNemar tests and area under the receiver operating characteristic curve (AUC) analyses were performed. The imaging and pathologic features of the discrepant lesions of the two protocols were analyzed., Results: The sensitivity of AB-MRI for lesion characterization tended to be lower than that of FD-MRI for all readers (58.8-82.4% vs. 79.4-100%), although the findings of only two readers were significantly different ( p < 0.05). The specificity of AB-MRI for lesion characterization was higher than that of FD-MRI for 80% of readers (39.0-74.0% vs. 19.5-45.5%, p ≤ 0.001). The AUC of AB-MRI was comparable to that of FD-MRI for all readers ( p > 0.05). Fifteen percent (5/34) of the cancers were false-negatives on AB-MRI. More suspicious margins or internal enhancement on the delayed phase images were related to the discrepancies., Conclusion: The overall performance of AB-MRI was similar to that of FD-MRI in distinguishing between benign and malignant lesions. AB-MRI showed lower sensitivity and higher specificity than FD-MRI, as 15% of the cancers were misclassified compared to FD-MRI., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

Effectively targeting and treating breast cancer stem cells (BCSCs), which have been linked to tumor development and metastasis, and recurrence still remains a challenging issue in preclinic and clinic. Screening and identifying characteristic BCSC biomarkers is important for distinguishing BCSCs from differentiated tumor cells within the tumor mass. Molecular imaging and nanotechnology are evolving as new fields that have a potentially high research and clinical impact. Developing the biocompatible contrast agents conjugated with high-affinity biomarker to selectively target BCSCs and is one of the key prerequisites for image-guided diagnosis and monitoring therapy of BCSCs. Very recently, we documented the extra domain-B fibronectin (EDB-FN), which is considered as a new putative biomarker for BCSCs (NDY-1 cell) derived from human breast carcinosarcoma. We here review BCSC-targeted theranostics in vitro and in vivo by delivering siRNA or drug using the nanoparticles conjugated with a small peptide specific to EDB-FN.

Diffusion-weighted magnetic resonance imaging (DW MRI) is a fast unenhanced technique that shows promise as a stand-alone modality for cancer screening and characterization. Currently, DW MRI may have lower sensitivity than that of dynamic contrast-enhanced MRI as a standalone modality for breast cancer detection but superior to that of mammography, which may provide a useful alternative for supplemental screening. Standardized acquisition and interpretation of DW MRI can improve the image quality and reduce the variability of the results. Furthermore, high-resolution DW MRI, with advanced techniques and postprocessing, will facilitate better detection and characterization of subcentimeter cancers and reduce false-negatives and false-positives. Future results from ongoing prospective multicenter clinical trials using standardized and optimized protocols will facilitate the use of DW MRI as a stand-alone modality., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2021 The Korean Society of Radiology.)