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.

TPS627 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% (in DCIS up to 30%). 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 most studies, the patient perspective, addressing e.g. discomfort and pain, 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, surgeon and radiologist satisfaction and economic impact. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://eubreast.org/melody ). MELODY is a prospective intergroup cohort study which enrolls female and male patients. planned for breast-conserving surgery with imaging-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, patient-reported outcomes, rates of “lost markers”, radiologist and surgeon satisfaction, and health economic evaluation of the different techniques. Target accrual is 7,416 patients. Enrollment started in January 2023. Until 24 January 2025, 3938 patients from 20 countries were enrolled in the study. The study is expected to complete patient enrollment in year 2026. The study will be conducted in 30 countries and is supported by the Oncoplastic Breast Consortium (OPBC), AWOgyn, AGO-B, SENATURK, the American Society of Breast Surgeons (ASBS) and the Korean Breast Cancer Study Group (KBCSG). Clinical trial information: NCT05559411 .

Purpose:As part of the pretherapeutic diagnostic workup for vulvar cancer, the inguinal lymph node status should be assessed. The diagnostic value of structured inguinal sonography for predicting the histological lymph node status in patients with vulvar cancer should be determined. Materials and Methods:All patients diagnosed with vulvar cancer and scheduled for surgical removal of inguinal lymph nodes were included in the prospective unicentric cohort study from March 2023 to May 2025. Preoperatively, inguinal ultrasound was performed according to the Vulvar International Tumor Analysis (VITA) protocol. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were determined. These were compared with the retrospectively collected results of an inguinal ultrasound examination, which was not performed according to the VITA protocol, in patients who had undergone surgery between January 2016 and February 2023. Results:Lymph node sonography performed according to the VITA protocol, followed by inguinofemoral surgery, was conducted in 74 groins. Lymph node metastases could be identified with a sensitivity of 64.3%, a specificity of 78.3%, a PPV of 40.9%, and an NPV of 90.4%. In 92 groin surgeries in patients without application of the VITA protocol, a sensitivity of 56.3%, a specificity of 89.5%, a PPV of 52.9%, and an NPV of 90.7% were determined, which did not differ significantly from the VITA cohort (p > 0.05). Conclusion:Overall, even after the introduction of a structured examination protocol specifically designed for vulvar cancer, inguinofemoral sonography did not demonstrate higher accuracy in determining the histological lymph node status.

Current de-escalation studies on axillary surgery for breast cancer in various clinical scenarios are investigating whether it is possible to reduce axillary interventions or even omit axillary surgery entirely in selected patients without compromising oncological outcomes. Existing study results clearly show that less invasive approaches to breast cancer treatment can be safe and effective in selected patients. De-escalation of axillary surgery reduces complications and improves patients' quality of life without compromising overall oncological cure rates. The integration of de-escalation strategies into clinical practice could bring about a paradigm shift in breast cancer treatment and pose new challenges for breast centers regarding the direction of interdisciplinary therapy.

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 .

Aktuelle Deeskalationsstudien zur Axillachirurgie untersuchen in verschiedenen klinischen Szenarien beim Mammakarzinom, ob eine Reduktion axillärer Interventionen oder sogar der Verzicht auf axilläre Eingriffe bei ausgewählten PatientInnen ohne Beeinträchtigung der onkologischen Ergebnisse möglich ist. Bereits vorliegende Studienergebnisse zeigen deutlich, dass weniger invasive Ansätze bei selektierten PatientInnen zur Behandlung des Mammakarzinoms sicher und effektiv sein können. Eine Deeskalation der axillären Chirurgie führt zu einer Minimierung von Komplikationen und einer Verbesserung der Lebensqualität der PatientInnen, ohne die übergeordneten onkologischen Heilungschancen zu beeinträchtigen. Die Integration der Deeskalationsstrategien in die klinische Praxis könnte einen Paradigmenwechsel in der Brustkrebsbehandlung bewirken und die Brustzentren vor neue Herausforderungen hinsichtlich der interdisziplinären Therapieausrichtung stellen.

Das axilläre Staging bildet einen integralen Bestandteil in der chirurgischen Behandlung des frühen Mammakarzinoms. Hier stellt bei Patientinnen mit initial klinisch und sonographisch unauffälligen Lymphknoten (cN0) die Sentinel-Lymphonodektomie (SLNE) sowohl bei primär geplanter Operation als auch nach Neoadjuvanz den Goldstandard dar. Nach der Publikation der ACOSOG-Z011-Studie wird bei cN0-Patientinnen mit primärer brusterhaltender Therapie und geplanter Bestrahlung auch bei postoperativ bis zu 2 befallenen Sentinel-Lymphknoten auf eine komplettierende axilläre Lymphonodektomie (ALNE) verzichtet. Der kürzlich publizierten SENOMAC-Studie zufolge kann in diesem Kollektiv auch nach Mastektomie auf die ALNE verzichtet werden, sofern eine axilläre Radiatio durchgeführt wird. Inwieweit diese Studie Einzug in die deutschen AGO(Arbeitsgemeinschaft Gynäkologische Onkologie)-Empfehlungen erhält, bleibt abzuwarten. Eine weitere potenzielle Deeskalation in der cN0-Gruppe, welche zurzeit in prospektiven Studien untersucht wird, stellt der komplette Verzicht auf die Axilla-Operation dar. Die ersten positiven Studienergebnisse (SOUND-Studie) liegen hier bereits vor. Bei nodal-positiven Patientinnen (cN+) und geplanter primären Operation bleibt die ALNE der chirurgische Standard. Bei cN+ Patientinnen mit bis zu 3 suspekten Lymphknoten und nodaler Komplettremission (ycN0/ypN0) im Rahmen der Neoadjuvanz ist eine Deeskalation der Axillaoperation möglich. In Deutschland wird hier aufgrund der niedrigen Falsch-negativ-Rate das Konzept der „targeted axillary dissection“ (TAD) verfolgt, welches SLNE mit Entfernung des Target-Lymphknotens kombiniert. Die prospektiven Daten zur onkologischen Sicherheit der TAD werden derzeit im Rahmen der multizentrischen Registerstudie AXSANA erhoben.

Background; Postoperative seroma formation is one of the most common and serious complications after breast surgery for primary breast cancer, especially in patients undergoing mastectomy with or without implant-based breast reconstruction. Seromas may lead to infections and wound dehiscence, which can result in implant loss. To date, the cause of seroma development has not yet been clarified. Recent data of the unicenter SerMa pilot study identified an association with immunological-inflammatory processes as a potential reason for seroma development. Trial Design:The main objective of the multicenter SerMa study is to identify a subgroup of patients with an increased risk of developing seromas based on immunological or inflammatory markers in a planned cohort of 2200 subjects. The study is designed as international, prospective cohort study in cooperation with the EUBREAST Network (European Breast Cancer Research Association of Surgical Trialists). Currently participating study groups are AGO-B, AWOgyn and OPBC. Patients with primary breast cancer or ductal carcinoma in situ (DCIS) planned for mastectomy with or without implant insertion can participate in this study (study group 1 and 2). Study group 3 includes patients at high risk for breast cancer planned for risk-reducing subcutaneous mastectomy and implant reconstruction. Study group 4 includes healthy women with implant insertion for exclusively cosmetic reasons. Furthermore, it is planned to initiate a registry for postoperative breast seromas (SerMaReg). Primary endpoints: To achieve the primary endpoint – the identification of a patient group with an elevated risk of developing a seroma - it is planned to examine the groups with and without postoperative seroma formation regarding immunological markers in seroma fluid as well as in blood samples. In addition, local microbiome analyses, as well as tumor analyses with focus on microenvironment will be performed to differentiate possible carcinoma-specific immunological processes. Secondary endpoints: To answer the question whether differences are caused by immunological or cancer-related reasons, groups with and without postoperative seroma formation as well as groups with or without breast cancer are compared. Current status of the study: The study started recruiting in April 2024, the first patients have been enrolled and the protocol has been confirmed for practicability. The study is currently expanding worldwide. Target accrual: 550 participants per group, therefore 2200 participants in total. Citation Format: Nina Ditsch, Melitta Koepke, Nicole Pochert, Udo Jeschke, Mariella Schneider, Matthias Reiger, Claudia Traidl-Hoffmann, Angelika Mattmer, Shirin Hunstiger, Jacqueline Sagasser, Christian Dannecker, Mathis Wild, Christian Hinske, Sarah Friedrich, Steffi Hartmann, Henning Kahl, David Krug, Natalia Krawczyk, Kerstin Stemmer, Regina Fluhrer, Andreas Raue, Maria Luisa Gasparri, Roland Reitsamer, Justyna Jelinska, Güldeniz Cakmak, Eduard Bonci, Rachel Wuerstlein, Visnja Fink, Vesna Bjelic-Radisic, Marc Thill, Christoph Heitmann, Walter Weber, Annette Lebeau, Hans-Christian Kolberg, Toralf Reimer, Rosa di Micco, Jana de Boniface, Oreste Gentillini, Michael Untch, Maggie Banys-Paluchowski, Thorsten Kuehn. Start of SerMa – EUBREAST 5 (Seroma of the Mammary Gland) study (NCT05899387) - On the way to identify women at risk of developing seroma after mastectomy [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 P3-10-29.

BACKGROUND:Gynecomastia (GM) is the most common abnormality of the male breast; it is benign and usually bilateral. GM is a manifestation of disease and not a diagnosis in itself. An important differential diagnosis of unilateral GM is breast cancer. METHODS:This narrative review is based on pertinent publications from 2010 onward that were retrieved by a PubMed search, with special attention to the guidelines of the AWMF and the European Academy of Andrology (EAA) and the recommendations of the German Society for Gynecology and Obstetrics. RESULTS:GM can occur physiologically in newborns, during puberty, and in men over age 65. The basic diagnostic evaluation of GM consists of a thorough history and physical examination (especially of the breast area and genitals), breast and testicular sonography, and laboratory testing for total testosterone (tT), estradiol (E2), luteinizing hormone (LH), human chorionic gonadotropin (hCG), and prolactin (PRL) levels. Further tests to be carried out as indicated according to the clinical findings include the determination of follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), fT4, alpha-1-fetoprotein (AFP), dehydroepiandrosterone (DHEA), and free testosterone (fT) levels, liver and kidney function tests, chromosomal analysis, and supplementary imaging procedures. The treatment depends on the underlying disease and the severity of symptoms, ranging from further observation alone to pharmacotherapy and surgery. Approximately 700 men receive a diagnosis of breast cancer each year in Germany. Because breast cancer in men is rare, there are no pertinent studies, and its treatment is analogous to the treatment of breast cancer in women as recommended in the guidelines. CONCLUSION:Men should be included in clinical trials of treatment for breast cancer whenever this is fea - sible, so that the evidence base can be enlarged and men can be given access to innovative treatment methods.

Surgical staging procedures of the axilla in initially clinically node-positive (cN +) breast cancer patients receiving neoadjuvant chemotherapy (NACT) vary across countries. Different procedures such as axillary lymph node dissection, sentinel lymph node biopsy, target lymph node biopsy and targeted axillary dissection are currently in use. To date, data on radar reflectors as a non-wire and non-radioactive technique for marking target lymph nodes are limited. The present study aims at examining the detection rate, the rate of lost markers, and magnetic resonance imaging artifacts after TLN marking using a radar reflector before NACT in the largest available cohort of breast cancer patients enrolled in the international prospective AXSANA study. AXSANA (EUBREAST-03) is an international prospective cohort study including cN + patients managed with different surgical axillary staging techniques after NACT. Eligible patients have cT1-4c cN + breast cancer and receive neoadjuvant chemotherapy. Patients are followed up for 5 years. In the present subgroup analysis, only patients with a TLN marked by a radar reflector were included. A TLN was marked by radar reflector insertion in 158 patients prior to NACT. Of these, 136 had final surgery results available at the time of analysis, and in 135 out of these 136 patients, localization of TLN was attempted. All radar markers were successfully removed. While lymphoid tissue corresponding to the TLN was identified in 132 patients (97.8

Background: Seroma formation is one of the most frequent complications after breast cancer (BC) surgery. One of the aims of the uni-center SerMa pilot study was to investigate the risk of patients for seroma development after mastectomy with or without implant reconstruction. The expression patterns of the programmed cell death protein 1 (PD-1) and its ligand (PD-L1) found in the tumor microenvironment (TME) of formalin-fixed paraffin-embedded (FFPE) tissue samples of BC patients were therefore of particular interest, since inhibitors against those molecules are currently used in BC treatment. Methods: The checkpoint molecules PD-1 and PD-L1 were immunohistochemically stained in 80 FFPE tissue samples of patients of the SerMa pilot study cohort and positive cells were evaluated. PD-1 positive cells in the TME were examined and the presence (yes/no) was determined. To assess whether the tumor was positive or negative regarding PD-L1 expression, the immune cell (IC) score, combined positive score (CPS) and tumor proportion score (TPS) were assessed by pathologists. Cells isolated from aspirated seroma fluids (SFl) of a sub-cohort of 18 patients were analyzed using flow cytometry to identify CD3+ T cells and CD68+ macrophages with their PD-1 and PD-L1 expression. Results: In 37 patients PD-1+ cells were detected in the TME and 15 out of the 80 were considered positive for PD-L1 (IC ≥1%; of those 4 had a CPS ≥10 and 3 a TPS ≥1%). Since we detected checkpoint molecules on our tissue samples, we were interested in their presence on cells of the SFl. We succeeded in measuring both PD-1 and PD-L1 on the surface of T cells as well as macrophages. Almost all analyzed SFl contained macrophages positive for PD-L1 (17 out of 18). In six out of the 18 SFl T cells were positive (>1%) for PD-1. In a next step, we compared the positivity of PD-1 and PD-L1 in cells of the SFl with the corresponding tissue samples (n=13). In three cases we found positive results for PD-L1 in both fluid and tissue, for PD-1 it was only 1 case. When comparing all patients with regard to negative or positive results for PD-1 and PD-L1 in tissue and SFl, there was no evidence of a significant positive or negative correlation. Additionally, there was no significant difference in PD-1 and PD-L1 expression in the TME between patients with and without seroma formation. However, dividing the cohort at the median age of 64 years we found significant differences between seroma developers and non-developers: the presence of PD-1+ cells in the TME of older patients (64 years and older) (p=0,032) as well as the CPS of younger patients (<64 years) (p=0,039) showed significance. Discussion and Outlook: To the best of our knowledge, this is the first study showing PD-1 and PD-L1 expression on T cells and macrophages of SFl. However it is still unclear, whether there is a relation between the PD-1/PD-L1 positive tissue cells and the later emerging immune cells of the SFl, since the sub-cohort presented here is too small to draw any conclusions. Further research is needed to investigate the role of PD1/PD-L1 expressing immune cells in the context of seroma development in the bigger study cohort of the multi-center international SerMa study (EUBREAST 5). Our first results suggest that in older patients the presence of PD1+ cells in the TME decreased the risk of developing a seroma significantly while older age is associated with a higher risk for seroma formation. Acknowledgements: The authors thank Prof. Dr. Bruno Märkl for the pathological evaluation of the tissue samples. Citation Format: Nina Ditsch, Nicole Pochert, Felicitas Schneider, Fritzi Schittek, Melitta Köpke, Udo Jeschke, Mariella Schneider, Aline Metz, Matthias Reiger, Claudia Traidl-Hoffmann, Christian Dannecker, Carl Mathis Wild, Ludwig Christian Hinske, Johanna Veh, Natalie Rohrmoser, Eva Leopoldsberger, Laura Bähner, Steffi Hartmann, Michael Untch, Maggie Banys-Paluchowski, Thorsten Kühn, Nina Ditsch. The expression patterns of the immune checkpoint molecules PD-1 and PD-L1 in the context of seroma development in breast cancer [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 P1-04-29.

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.