PURPOSE:Surgical axillary staging in patients with node-positive breast cancer (BC) who converted to clinical node negativity through neoadjuvant chemotherapy (NACT) has changed significantly in recent years. Targeted axillary dissection (TAD) and target lymph node (TLN) biopsy (TLNB) became increasingly popular. However, data comparing marking techniques for the TLN are limited. Here, we evaluate marking techniques in the largest prospective cohort worldwide. MATERIALS AND METHODS:Among patients from the ongoing prospective multicenter AXSANA (EUBREAST-03) study who received TLN marking and TAD/TLNB, we evaluated different marking methods with respect to detection and removal rates and clinical performance. RESULTS:Until January 6, 2025, 6,129 patients from 26 countries were enrolled. Of these patients, 2,596 had ≥1 TLN marked before NACT and completed surgery; 13.3% of the patients had ≥4 suspicious nodes at diagnosis. Pre-NACT TLN marking used a clip in 2,003 patients (77.2%), magnetic seed in 287 (11.1%), carbon ink in 192 (7.4%), radar marker in 119 (4.6%), radioactive seed in 18 (0.7%), radiofrequency identification device (RFID) in 12 (0.5%), or other methods in two (0.1%). One TLN was marked in 2,427 patients (93.5%), two TLNs in 138 (5.3%), and ≥3 in 27 patients (1%). Targeted removal of the TLN was planned in 2,100 patients (80.9%; TAD in 2,076 [80.0%] and TLNB in 24 [0.9%]). The TLN was detected and removed by TAD/TLNB in 1,915 patients (91.2%). TLN detection rate was the highest in patients whose TLNs were marked pre-NACT with markers suitable for probe-guided detection (96.6%; radioactive seed: 100%, magnetic seed: 96.9%, radar marker: 96.1%, RFID: 90%), followed by carbon ink (94.9%) and clip (89.6%; P < .001). CONCLUSION:This large prospective analysis of patients with initially clinically node-positive BC receiving NACT demonstrates that probe-guided detection markers used to mark metastatic nodes before NACT provide superior detection rates.

Zusammenfassung Bei Patientinnen mit hormonrezeptorpositivem (HR+) Brustkrebs im Frühstadium (early breast cancer, EBC) reduziert die adjuvante endokrine Therapie (ET) signifikant das Rezidiv- und das Mortalitätsrisiko. Eine gängige Methode zur Messung der Therapie-Adhärenz ist die direkte Befragung der Patientinnen. Allerdings kann diese Methode aufgrund der Verzerrung durch soziale Erwünschtheit ungenau sein. Daher war das Ziel dieser Studie, die Adhärenz zur ET über die ersten 5 Behandlungsjahre mithilfe von Abrechnungsdaten eines großen deutschen Krankenversicherers (AOK Baden-Württemberg) zu analysieren.In die Analyse wurden Patientinnen mit der Diagnose HR-positiver EBC einbezogen, die zwischen dem 1. Juli 2010 und dem 31. Dezember 2019 stationär behandelt wurden und sich einer Brustkrebs-Operation unterzogen haben. Die Adhärenz zur ET wurde als das Verhältnis zwischen der Summe der Tablettenanzahl aus eingelösten Rezepten und der Dauer der ET in Tagen definiert (beginnend ab der ersten Verschreibung nach Abschluss der Operation und Chemotherapie). Die Anwendung der ET wurde über 5 Jahre beobachtet. Eine niedrige Adhärenz lag bei einem Verhältnis von weniger als 0,8 vor, während eine hohe Adhärenz einem Verhältnis von 0,8 oder mehr entsprach. Das fernrezidivfreie Überleben (distant recurrence-free survival, DRFS) wurde vom Tag der Erstdiagnose des EBC bis zum Auftreten eines Fernrezidivs berechnet. Das Gesamtüberleben (overall survival, OS) wurde als der Zeitraum zwischen der Erstdiagnose des EBC und dem Tod jeglicher Ursache definiert.Insgesamt wurden 16642 Patientinnen mit EBC in die Studie eingeschlossen. Davon zeigten 4303 (86%) im ersten Jahr nach Therapiebeginn eine hohe Adhärenz zur ET. Nach 5 Jahren hielten 68% der Patientinnen eine hohe Adhärenz aufrecht. Eine kontinuierlich hohe Adhärenz zur ET hatte einen signifikanten Einfluss auf das DRFS (HR: 0,66%; 95-%-KI: 0,58–0,76, p > 0,0001) und OS (HR 0,52, 95%-KI: 0,47–0,57, p < 0,0001).Zusammenfassend ist festzuhalten, dass die Adhärenz zur ET ein unabhängiger Risikofaktor ist, der DRFS und OS signifikant beeinflusst. In weiteren Real-World-Studien sollten die Faktoren untersucht werden, die zum Behandlungsabbruch beitragen, und es sollten prospektive Strategien zur Verbesserung der Adhärenz evaluiert werden.

Introduction:The primary objective of breast-conserving surgery (BCS) is complete excision of the tumor with histologically negative margins (R0 resection). Intraoperative ultrasound (IOUS) has been shown to reduce re-excision rates (R1) for sonographically visible breast cancer. However, a standardized IOUS technique has not yet been established. This study aimed to evaluate whether standardization using the "Tübingen Ultrasound Ruler" can reduce R1 resection rates. Patients and Methods:This retrospective study included 273 patients who underwent BCS between January 2020 and December 2023 for unilateral or bilateral ductal carcinoma in situ and/or invasive breast cancer, regardless of tumor biology, the presence of microcalcifications, or prior chemotherapy. All surgeries were performed by a single surgeon. Tumors were excised with a sonographically assessed margin of >10 mm in all directions. After specimen imaging, additional margin shavings were obtained when indicated. Results:A total of 282 specimens were analyzed, with a mean specimen weight of 110.5 g. Considering the main resection specimen alone, the R1 rate was 18.8%. Targeted IOUS-guided shavings significantly reduced the R1 rate to 8.5%. Compared with the mean R1 rate of the average figures of OnkoZert-certified breast centers reported between 2020 and 2023 (12.34%), the use of the "Tübingen Ultrasound Ruler" in combination with specimen imaging was associated with a significantly lower R1 rate (p = 0.043). Conclusion:Standardization of the IOUS technique combined with imaging-guided targeted shavings makes it possible to achieve a low R1 rate (8.5%) in breast-conserving surgery.

Importance Positive margins occur in 12% to 30% of breast-conserving surgeries and are associated with increased local recurrence risks. Accurate and efficient intraoperative margin assessment, therefore, remains an unmet clinical need. Objective To evaluate the success rate of intraoperative specimen positron emission tomography (PET)–computed tomography (CT) imaging in addressing positive margins in patients with invasive ductal carcinoma. Design, Setting, and Participants This was an interventional, multicenter, nonrandomized clinical trial that recruited patients from June 2022 to March 2025. Patients were followed up 2 weeks after surgery. Six European breast cancer centers participated and integrated specimen PET-CT imaging into their routine surgical flow. The analysis included eligible patients with early-stage breast cancer scheduled for breast-conserving surgery. Interventions Patients received an intravenous injection of low-dose 18 F-fluorodeoxyglucose (FDG; 0.8 MBq/kg). After tumor excision, the specimen was imaged intraoperatively using a dedicated specimen PET-CT scanner. Surgeons interpreted PET-CT images intraoperatively, and additional tissue was excised when margins were deemed suspicious to achieve final negative margins. Main Outcomes and Measures The primary outcome was the success rate of specimen PET-CT in addressing positive margins for the invasive component in patients undergoing breast-conserving surgery for invasive ductal carcinoma. Secondary outcomes included success rates in other breast cancer subtypes, final positive margin rates, reoperation rates, and diagnostic performance using histopathology as the reference standard. Results The analysis cohort consisted of 148 female patients with a median (IQR) age of 65 (53-73) years and a median (IQR) preoperative tumor size of 17 (12-22) mm. For the invasive component of invasive ductal carcinoma, success rates increased from 83.3% (70 of 84 patients) without intraoperative margin assessment (IMA) to 86.9% (73 of 84 patients) with routine margin assessment and to 95.2% (80 of 84 patients) with specimen PET-CT ( P < .001 vs no IMA). Across all study groups, success rates improved from 76.4% (113 of 148 patients) without IMA to 81.8% (121 of 148 patients) with routine margin assessment techniques and to 91.9% (136 of 148 patients) with specimen PET-CT ( P < .001 vs no IMA; P = .009 vs standard-of-care IMA). Conclusions and Relevance Study findings show that specimen PET-CT imaging was associated with an improvement in the assessment of positive margins for invasive component in patients undergoing conserving surgery for early breast cancer. The use of this integrated approach might lead to a substantial reduction of re-excision rates after breast-conserving surgery. Trial Registration ClinicalTrials.gov Identifier: NCT04999917

Ultrasound examination is a vital imaging tool in medicine, yet opportunities for comprehensive theoretical and practical training during medical education are limited. Effective ultrasound education requires both theoretical knowledge and hands-on practice. To address this, we developed SonoGame, a gamified platform designed to teach ultrasound skills to medical students. SonoGame provides a step-by-step introduction to ultrasound imaging and aims to improve skills such as image orientation, spatial visualization, and hand-eye-coordination through mini-games using geometric objects. This study evaluates the impact of SonoGame training on ultrasound skills.In this prospective, single-center study, 56 medical students, the majority of whom had no prior ultrasound experience, were randomly assigned to either a control group or a SonoGame group. The SonoGame group trained with the platform in four 30-minute sessions over 4 weeks, while the control group received no training. Ultrasound skills were assessed in both groups before and after the training period.The SonoGame group showed significant improvement in ultrasound skills, particularly with complex anatomical structures, compared to the control group. Participants in the SonoGame group also reported increased familiarity and confidence with sonography, viewing SonoGame as a valuable tool in their training.SonoGame is an effective supplement to conventional ultrasound education, enhancing the skills necessary for ultrasound examinations in medical students.

Abstract Antiestrogenic therapy is widely used in the treatment of hormone receptor–positive breast cancer and alters estrogen signaling through different mechanisms, which may affect brain regions sensitive to estrogenic modulation. However, its early effects on brain architecture remain poorly understood. In this study, we examined whether the initiation of antiestrogenic therapy (tamoxifen or letrozole) is associated with short-term changes in brain structure and psychological symptoms, and whether these changes differ between the two treatment types. For now, data from twenty women with breast cancer and twenty healthy controls undergoing MRI scanning and psychological assessments at baseline (t1) and again approximately 2–3 weeks later (t2) were used. Patients started antiestrogen therapy immediately after the first assessment. Structural analyses included whole-brain cortical thickness and gyrification, as well as region-of-interest measures of hippocampal and amygdala volume. Changes in psychological parameters were also assessed, and hormone levels were measured but are not reported here. No robust time-by-group effects were observed for total brain volume, cortical thickness, gyrification, or hippocampal and amygdala volume after correction for multiple comparisons. An exploratory within-patient analysis identified a localized increase in cortical thickness in the right anterior insula/inferior frontal operculum; however, the corresponding time-by-group interaction was not significant. Somatic depressive symptom scores showed a significant time-by-group interaction, with scores increasing in the breast cancer group but remaining stable in healthy controls. Across time points, women with breast cancer also reported higher overall depressive symptoms and state anxiety and lower positive affect than healthy controls. Exploratory associations between changes in brain structure and psychological symptoms were observed at uncorrected thresholds but did not survive correction for multiple comparisons. In this interim sample, no robust group-level macrostructural brain changes were detected over the first 2–3 weeks following initiation of antiestrogen therapy. However, this does not exclude the possibility of early structural effects, which may be subtle or heterogeneous and therefore difficult to detect in the current sample. Somatic depressive symptoms increased in the BC group relative to healthy controls during this early treatment period, while exploratory neural findings suggested potential localized changes and individual-difference associations that warrant cautious interpretation and require confirmation in larger samples. Recruitment is ongoing toward the prospectively defined final sample.

Importance:Positive margins occur in 12% to 30% of breast-conserving surgeries and are associated with increased local recurrence risks. Accurate and efficient intraoperative margin assessment, therefore, remains an unmet clinical need. Objective:To evaluate the success rate of intraoperative specimen positron emission tomography (PET)-computed tomography (CT) imaging in addressing positive margins in patients with invasive ductal carcinoma. Design, Setting, and Participants:This was an interventional, multicenter, nonrandomized clinical trial that recruited patients from June 2022 to March 2025. Patients were followed up 2 weeks after surgery. Six European breast cancer centers participated and integrated specimen PET-CT imaging into their routine surgical flow. The analysis included eligible patients with early-stage breast cancer scheduled for breast-conserving surgery. Interventions:Patients received an intravenous injection of low-dose 18F-fluorodeoxyglucose (FDG; 0.8 MBq/kg). After tumor excision, the specimen was imaged intraoperatively using a dedicated specimen PET-CT scanner. Surgeons interpreted PET-CT images intraoperatively, and additional tissue was excised when margins were deemed suspicious to achieve final negative margins. Main Outcomes and Measures:The primary outcome was the success rate of specimen PET-CT in addressing positive margins for the invasive component in patients undergoing breast-conserving surgery for invasive ductal carcinoma. Secondary outcomes included success rates in other breast cancer subtypes, final positive margin rates, reoperation rates, and diagnostic performance using histopathology as the reference standard. Results:The analysis cohort consisted of 148 female patients with a median (IQR) age of 65 (53-73) years and a median (IQR) preoperative tumor size of 17 (12-22) mm. For the invasive component of invasive ductal carcinoma, success rates increased from 83.3% (70 of 84 patients) without intraoperative margin assessment (IMA) to 86.9% (73 of 84 patients) with routine margin assessment and to 95.2% (80 of 84 patients) with specimen PET-CT (P < .001 vs no IMA). Across all study groups, success rates improved from 76.4% (113 of 148 patients) without IMA to 81.8% (121 of 148 patients) with routine margin assessment techniques and to 91.9% (136 of 148 patients) with specimen PET-CT (P < .001 vs no IMA; P = .009 vs standard-of-care IMA). Conclusions and Relevance:Study findings show that specimen PET-CT imaging was associated with an improvement in the assessment of positive margins for invasive component in patients undergoing conserving surgery for early breast cancer. The use of this integrated approach might lead to a substantial reduction of re-excision rates after breast-conserving surgery. Trial Registration:ClinicalTrials.gov Identifier: NCT04999917.

505 Background: Axillary lymph node dissection (ALND) for node-positive breast cancer (BC) converting to clinical node-negativity after neoadjuvant chemotherapy (NACT) is increasingly being replaced by less invasive procedures, such as sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD). Concerns remain regarding the use of de-escalated procedures in patients with high initial nodal burden. We aimed to determine factors associated with nodal response, with a focus on tumor biology and nodal burden, to enable less extensive surgery without compromising oncological outcomes. Methods: AXSANA is an ongoing study investigating oncological and patient-reported outcomes after different axillary procedures in cN+ BC treated with NACT. In the present analysis, the impact of nodal involvement and tumor biology on axillary response was analyzed. The entire dataset is continuously and systematically monitored for data quality assurance. Results: 7,071 patients from 288 sites in 26 countries were included between June 2020 and January 7 th , 2026. Of these, 5,262 had completed surgery at the time of analysis. 2,341 patients (44.5%) had HR+ HER2- disease, followed by HR+ HER2+ (1,244; 23.6%), triple-negative (1,053; 20.1%) and HR- HER2+ (618; 11.7%). 91.3% of patients had an invasive ductal carcinoma of no special type (NST). 1,158 (22.1%) had ≥ 4 suspicious nodes at time of diagnosis. The highest nodal pCR rate (ypN0) was observed in patients with HR- HER2+ disease (86.1%), followed by HR+ HER2+ (70.7%), triple-negative (68.5%), and HR+ HER2- (30.5%; p < 0.001). Nodal pCR rate was higher in patients with NST tumors (55.6%), compared to those with invasive lobular (35.2%) and mixed histology (43.8%; p < 0.001). Patients with higher Ki67 (p < 0.001), higher grading (p < 0.001), multicentric tumors (p = 0.001), and without lymphangitis carcinomatosa (p = 0.046) were more likely to achieve nodal pCR in the univariate analysis. In contrast, the number of suspicious nodes at the time of diagnosis was not associated with axillary response (ypN0: 54.4% in pts. with 1-3 suspicious nodes vs. 53.6% in ≥ 4 suspicious nodes; p = 0.670). In the multivariable analysis, receptor status, Ki67, and grading, but not the number of suspicious lymph nodes at the time of diagnosis, were significantly associated with axillary response to treatment. Conclusions: This large prospective analysis shows that tumor biology, rather than the extent of nodal involvement is associated with axillary response to NACT. This challenges current guidelines and the common approach of restricting surgical de-escalation to patients with a low axillary tumor burden at presentation, and suggests that the selection of candidates for a potential de-escalation should be based on tumor biology rather than the extent of axillary disease at diagnosis. Clinical trial information: NCT04373655 .

OBJECTIVE:Sentinel lymph node biopsy (SLNB) is considered an essential step in the surgical management of endometrial and cervical cancers as it has led to a reduction in the need for full pelvic lymphadenectomy. This proof-of-concept study aimed to evaluate the feasibility and diagnostic performance of intraoperative sonographic assessment of sentinel lymph nodes (SLNs) during laparoscopic and robotic surgeries for endometrial and cervical cancers. METHODS:This was a prospective, single-center, non-interventional diagnostic feasibility study conducted between October 2023 and July 2024 at the University Women's Hospital, Tübingen, Germany, and registered at the German Clinical Trials Register (DRKS00032919). A total of 20 patients underwent intraoperative sonographic SLN evaluation using a sterile drop-in ultrasound probe prior to resection. The assessment was based on the Vulvar International Tumor Analysis (VITA) criteria that includes parameters, such as lymph node shape, cortical thickening, vascularization, and echogenicity. Findings were correlated with histopathologic results to determine diagnostic accuracy. To assess the diagnostic accuracy of the sonographic criteria, a receiver operating characteristic (ROC) analysis was conducted, focusing on sensitivity and specificity with respect to lesion dignity classification (benign vs malignant). RESULTS:Among the 25 initially prepped patients, 20 successfully underwent intraoperative sonographic SLN evaluation, while five were excluded due to logistical issues or consent withdrawal. A total of 49 SLNs were analyzed, and the analysis included histopathologic confirmation. The sonographic assessment demonstrated perfect sensitivity and specificity of 1.0 as reflected by the area under the ROC curve (AUC = 1.0). No adverse events were reported. CONCLUSION:The study confirms that intraoperative sonographic evaluation of SLNs in minimally invasive gynecologic oncology surgeries is feasible, safe, and highly accurate. This technique may serve as a valuable adjunct to current SLNB protocols and lead to a potential reduction in the need for extensive lymphadenectomy while concurrently maintaining diagnostic reliability. Further research using larger cohorts is warranted to validate these findings and assess broader clinical applicability.

PURPOSE:Shear wave elastography (SWE) has been investigated as a complement to B-mode ultrasound for breast cancer diagnosis. Although multicenter trials suggest benefits for patients with Breast Imaging Reporting and Data System (BI-RADS) 4(a) breast masses, widespread adoption remains limited because of the absence of validated velocity thresholds. This study aims to develop and validate a deep learning (DL) model using SWE images (artificial intelligence [AI]-SWE) for BI-RADS 3 and 4 breast masses and compare its performance with human experts using B-mode ultrasound. METHODS:We used data from an international, multicenter trial (ClinicalTrials.gov identifier: NCT02638935) evaluating SWE in women with BI-RADS 3 or 4 breast masses across 12 institutions in seven countries. Images from 11 sites were used to develop an EfficientNetB1-based DL model. An external validation was conducted using data from the 12th site. Another validation was performed using the latest SWE software from a separate institutional cohort. Performance metrics included sensitivity, specificity, false-positive reduction, and area under the receiver operator curve (AUROC). RESULTS:The development set included 924 patients (4,026 images); the external validation sets included 194 patients (562 images) and 176 patients (188 images, latest SWE software). AI-SWE achieved an AUROC of 0.94 (95% CI, 0.91 to 0.96) and 0.93 (95% CI, 0.88 to 0.98) in the two external validation sets. Compared with B-mode ultrasound, AI-SWE significantly reduced false-positive rates by 62.1% (20.4% [30/147] v 53.8% [431/801]; P < .001) and 38.1% (33.3% [14/42] v 53.8% [431/801]; P < .001), with comparable sensitivity (97.9% [46/47] and 97.8% [131/134] v 98.1% [311/317]; P = .912 and P = .810). CONCLUSION:AI-SWE demonstrated accuracy comparable with human experts in malignancy detection while significantly reducing false-positive imaging findings (ie, unnecessary biopsies). Future studies should explore its integration into multimodal breast cancer diagnostics.

Breast ultrasound has been established for many years as an important method in addition to mammography for clarifying breast findings. The goal of the Best Practice Guidelines Part III of the DEGUM breast ultrasound working group is to provide colleagues working in senology with information regarding the specific medical indications for breast ultrasound in addition to the current ultrasound criteria and assessment categories published in part I and the additional and optional sonographic diagnostic methods described in part II. The value of breast ultrasound for specific indications including follow-up, evaluation of breast implants, diagnostic workup of dense breast tissue, diagnostic workup during pregnancy and lactation, and the diagnostic workup of breast findings in men is discussed. Each section after the general information section contains a description of specific pathologies followed by a short summary and DEGUM recommendations for the particular indications. The latest S3 guidelines and AGO guidelines were taken into consideration.

PURPOSE:Omission of sentinel lymph node biopsy (SLNB) in selected hormone receptor-positive (HR+), HER2-negative (HER2-) early breast cancer patients has demonstrated safety in prospective trials. However, accurate axillary staging remains important for identifying candidates for adjuvant CDK4/6 inhibitor therapy. We quantified the impact of SLNB omission on CDK4/6 eligibility and explored predictors of occult nodal disease in a real-world cohort. METHODS:We retrospectively analyzed 948 patients treated 2014 to 2022 at Tübingen University Hospital who met criteria proposed for potential SLNB omission: age ≥ 50 years, cT1 cN0, HR+/HER2-, grade 1 to 2 tumors treated with breast-conserving surgery and whole-breast irradiation. We assessed the prevalence of occult nodal metastases and potential eligibility for adjuvant abemaciclib (monarchE-criteria) or ribociclib (NATALEE-criteria) based on final pathology and fitted multivariable logistic models. RESULTS:Among 948 patients meeting SLNB omission criteria, 143 (15.1%) harbored occult nodal disease. Of these node-positive patients, 17 fulfilled the criteria for abemaciclib eligibility. For ribociclib, 105 node-positive patients were eligible. On multivariable analysis, multifocality (OR = 2.3; P ≤ .001) and cT1c tumor stage (OR = 1.76; P = .008) predicted axillary upstaging; invasive lobular carcinoma (ILC) showed higher crude upstaging than IDC/NST (22.6% vs. 14.0%) but did not retain independent significance after adjustment. CONCLUSIONS:Omitting sentinel node biopsy in selected patients leads to under-detection of nodal metastasis in a relevant proportion of patients, particularly with cT1c tumors, multi-focal tumors and ILC. As these patients may benefit from more intensive adjuvant treatment, omission of sentinel-node biopsy should be part of decision-making. Future trials should investigate the impact of adjuvant treatment for patients with occult lymph node metastases.

Male breast cancer (BC) is a rare entity and represents a significant clinical challenge due to its late diagnosis and resulting poorer prognosis compared to female BC. As shown by prior studies, approximately 99

BACKGROUND:Assessing the axillary response to neoadjuvant chemotherapy (NACT) in patients with initially node-positive breast cancer is crucial to determine the most appropriate surgical approach. While axillary ultrasound (AUS) is a well-established tool in the upfront surgery setting, its performance after NACT is still questioned. Here, we assess the reliability of AUS in predicting the pathological axillary status after NACT using data from the large prospective multicenter AXSANA trial. METHODS:Between June 1, 2020, and May 31, 2024, 5.559 patients were enrolled in the AXSANA trial. For this analysis, patients with clinically node-positive breast cancer who underwent AUS after NACT were eligible. AUS`s sensitivity, specificity, positive (PPV) and negative predictive value (NPV) were analyzed using surgical staging as reference. FINDINGS:3840 patients were eligible for this analysis. Of these, 3428(89.3 %) patients underwent preoperative AUS after NACT, classified as unclear in 168(4.9 %), positive in 1060(30.9 %) and negative in 2200 (64.2 %). An axillary pathological complete response (pCR) was achieved in 1793(55.0 %). Nodal metastases were detected in 786 of 2200 patients (35.7 %) with an negative AUS, while 379(35.8 %) of 1060 patients with a positive AUS achieved an axillary pCR. AUS sensitivity was 46.4 %(95 % CI 43.8 %-49.0 %), specificity 78.9 %(76.9 %-80.7 %), PPV 64.2 %(61.3 %-67.1 %), and NPV 64.3 %(62.2 %-66.3 %). PPV was highest for HR+ /HER2- tumors (81.9 %, 78.9 %-85.2 %), NPV for HR-/HER2 + tumors (88.3 %, 84.2 %-91.7 %). Triple negative and HER2 + subtypes were significantly less frequently associated with false-negative AUS results than an HR+ /HER2- cancer. INTERPRETATION:AUS alone does not reliably predict pathological nodal status. Axillary lymph node dissection based on positive AUS findings after NACT results in surgical overtreatment. Surgical axillary staging after NACT remains essential for the accurate assessment of axillary lymph node status in patients with initially node-positive breast cancer.

Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins and re-operations are limited. In the majority of studies, the patient’s perspective with regard to discomfort and pain level has not been evaluated. The aim of MELODY (MEthods for LOcalization of Different types of breast lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://melody.eubreast.com). MELODY is a prospective intergroup cohort study which enrolls female and male patients requiring breast-conserving surgery and image-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal, independent of margin status on final histopathology, and 2) Negative resection margin rates at first surgery. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, comparison of patient-reported outcomes, rates of “lost markers” and diagnostician/radiologist’s and surgeon’s satisfaction as well as the health economic evaluation of the different techniques. Target accrual: 7,416 patients. Enrollment started in January 2023. The study is being conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B and SENATURK. Financial support was provided by Endomag, Merit Medical, Sirius Medical and Hologic. Citation Format: Maggie Banys-Paluchowski, Nina Ditsch, Thorsten Kühn, James Harvey, Nuh Zafer Canturk, Neslihan Cabioglu, Tove Filtenborg Tvedskov, Lina Pankratjevaite, Maria Luisa Gasparri, Dawid Murawa, Jai Min Ryu, Oreste Davide Gentilini, Rosa Di Micco, Mah Muneer Khan, Aoife Lowery, Natalia Krawczyk, Steffi Hartmann, Isabel T. Rubio, Antonio J. Esgueva, Jana de Boniface, Andreas Karakatsanis, Rajiv V. Dave, Shelley Potter, Ashutosh Kothari, Walter Paul Weber, Güldeniz Karadeniz Cakmak, Markus Hahn, Michael Patrick Lux, Marjolein Smidt, Bahadir M. Gulluoglu, Michaelis Kontos, Florentina Peintinger, Lia Pamela Rebaza, Maria Antónia Vasconcelos, Mariana Correia, Sarah Nietz, Francois Malherbe, Severine Alran, Khaled Mohammad Abdelwahab, Veronica Yamila Fabiano, Svs Deo, Yazan Masannat, Katharina Jursik, Bilge Aktas Sezen, Meldoy Study Group. MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4 / iBRA-NET, NCT 05559411) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-12-16.