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.

Germline BRCA1 and BRCA2 mutations enable targeted therapies in human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC). The two poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors olaparib and talazoparib were introduced into clinical practice in 2018. Limited evidence about their routine clinical use highlights the importance of this analysis. We provide a real-world analysis for PARP-inhibitor use in ABC patients treated within the prospective German PRAEGNANT registry (NCT02338167). 152 patients with ABC receiving a PARP-inhibitor were included. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated for all patients using the Kaplan-Meier method. Subgroups (line of therapy, metastasis timing, hormone receptor (HR) status, treatment: olaparib, talazoparib, among others), germline BRCA1, BRCA2 and PALB2 mutations and adverse events (AEs) were analyzed. The median rwPFS was 6.2 months (95% CI, 4.8-7.9) and the median rwOS was 17.1 months (95% CI, 14.4-22.3). Line of therapy, HR status and treatment (olaparib versus talazoparib) appeared to especially affect both rwPFS and rwOS. Among patients with a reported germline mutation, 36.1% had a BRCA1, 62.9% a BRCA2 and 1.0% a PALB2 mutation. In summary, outcomes were comparable to those reported in pivotal trials despite later-line use of PARP-inhibitors in this analysis.

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 .

BACKGROUND:(Likely) pathogenic variants (pVs) in hereditary breast and/or ovarian cancer (HBOC) genes increase cancer risk, but the clinical implications of multiple pVs remain insufficiently understood. METHODS:Using data from the prospective nationwide German Consortium for HBOC registry, we conducted a case-control study of genotype-phenotype associations, matching female carriers to compare cancer risk and disease severity between multiple and single heterozygous (SH) pV carriers. RESULTS:Among 26,983 carriers of single or multiple HBOC-associated pVs, 409 individuals had multiple heterozygosities, including 400 double heterozygous (DH) carriers. In a subcohort tested for 13 core genes, 98/3407 (2.9%) individuals had multiple HBOC-associated pVs. Breast cancers (BCs) in DH women with pVs in BRCA1 and another gene were predominantly triple-negative, even when the second, non-BRCA1 pV was typically associated with hormone receptor (HR)-positive BC. By contrast, BRCA1/CHEK2 DH carriers showed more HR-positive BCs than BRCA1 SH women. The median age at first BC was similar in female ATM/CHEK2 DH carriers and BRCA1 SH carriers (41.5 [IQR 14.0] vs. 41.3 [14.1] years). Matched BRCA1 and BRCA2 SH carriers were less likely to present with higher disease severity than BRCA1/BRCA2 DH carriers (BRCA1: OR 0.396 [0.180-0.87]; BRCA2: OR 0.224 [0.100-0.50]). CONCLUSIONS:Multiple heterozygosity in HBOC core genes is more frequent than previously assumed. Our data indicate that gene-gene constellations can reshape tumour phenotype and clinical severity rather than following single-gene expectations. Integrating multiple pVs into risk assessment and counselling may enhance personalised surveillance and risk-reducing strategies for DH individuals and their families in the era of widespread multigene testing.

Biomarkers are integral to modern breast cancer management by providing essential information for prognosis and treatment selection. This review presents the 2026 update of the recommendations of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) on therapy-relevant prognostic and predictive biomarkers. The recommendations are based on a structured evaluation of the most recent and clinically relevant evidence using the AGO grading system to support decision-making in routine clinical practice.

[This corrects the article DOI: 10.1055/a-2612-3790.].

The German Guideline Committee (AGO: Working Group on Gynecologic Cancers) updated its yearly recommendations on the diagnosis and treatment of breast cancer in March 2026. Chapters on oncological and oncoplastic-reconstructive surgery are coordinated with the Working Group for Plastic, Aesthetic, and Reconstructive Surgery in Gynecology (AWOgyn). The most important changes include the ommission of sentinel lymph node biopsy (SLNB) and preffered axillary staging in patients with node-positive breast cancer undergoing neoadjuvant chemotherapy (NACT). Targeted axillary dissection (TAD) is endorsed as the method of choice [AGO ++] in patients converting from cN + to ycN0 status, and other de-escalated techniques (SLNB, target lymph node biopsy [TLNB]) are also possible options [AGO +]. Following NACT, ALND is indicated only when macrometastatic disease is detected in the sentinel and/or in the target lymph node.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2026 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

Genomics-guided precision oncology has improved survival in cancer entities with actionable mutations but cannot capture oncogenic signaling that manifests at the protein level. Here, we report a prospective, real-world pan-cancer study profiling proteomes and phosphoproteomes of 1,998 tumor samples from adults and children with rare or advanced cancers enrolled in the German precision oncology programs DKFZ/NCT/DKTK MASTER, CATCH and INFORM and their molecular tumor boards (MTBs). We developed tumor proteome activity status (TOPAS) scores for 46 clinically relevant kinases, an immune activity score capturing antigen presentation and T-cell activation and identified therapeutically targetable cell-surface proteins for 94% of patients. These readouts enhance MTB recommendations by exposing actionable non-genomic kinase activity, refining interpretation of oncogenic genome alterations, and highlighting cell-surface treatment options. Three proof-of-concept analyses indicate clinical utility including kinase activity-stratified pazopanib response in sarcoma, immune activity score-tracked checkpoint-inhibitor outcomes pan-cancer, and a phosphoproteomic biomarker distinguishing EGFR-inhibitor response in chordoma.

Studien in der Adjuvanz konnten zeigen, dass selbst bei 1 bis 2 Sentinel-Metastasen auf eine axilläre Lymphonodektomie (ALND) verzichtet werden kann, wenn eine brusterhaltende Operation bzw. Mastektomie mit einer begleitenden Strahlentherapie durchgeführt wird. Die notwendigen Zielvolumina der Strahlentherapie sind aber weiterhin noch nicht klar definiert. Aktuelle Studiendaten ermöglichen bei hormonrezeptorpositiven Tumoren mit niedrigem Risikoprofil bereits den kompletten Verzicht auf axilläre Eingriffe bei gleicher onkologischer Sicherheit. Zu beachten ist lediglich die Konsequenz eines nicht bekannten axillären Lymphknotenstatus hinsichtlich der weiteren adjuvanten Therapiemöglichkeiten, die sich z. B. für den Einsatz von CDK(„cyclin-dependent kinase“)-4/6- oder PARP(Poly[ADP-Ribose]Polymerase)-Inhibitoren ergeben könnten. Die Möglichkeit der Vermeidung einer ALND besteht auch im neoadjuvanten Setting. Auch bei Nachweis isolierter Tumorzellen und Mikrometastasen wird eine ALND nicht mehr generell empfohlen.

Background: The “International Consensus Conference for Advanced Breast Cancer” was initiated with the rationale to standardize treatment of advanced breast cancer (ABC) based on available evidence. The aim was to ensure that all ABC patients worldwide receive adequate treatment and get access to new diagnostic, therapeutic, and supportive options. Topics of ABC8: Since the beginning ABC Consensus Conference has been organized in Lisbon/Portugal. The 8th International Consensus Conference for ABC (ABC8) took place there from November 4th to 8th, 2025, and focused not only on metastatic disease but also on locally advanced and inflammatory breast cancer (BC). Special topics were new drugs and new therapies with promising results in randomized clinical trials. Not all of them are currently approved by FDA (Food and Drug Administration) or EMA (European Medicines Agency) for the indication in which the study was conducted. As in previous years, patient advocates from around the world were integrated into the ABC Conference and contributed substantially to the consensus. Rationale for the Manuscript: A German BC expert panel comments on the voting results of the ABC8 panelists regarding their relevance for routine clinical practice in Germany. As with previous meetings, the ABC8 votes focused on modified or new statements. Statements not modified for the ABC8 consensus remain valid. The German comments are always based on the current recommendations of the “Breast Committee” of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie, AGO Mamma).

BackgroundFor more than 30 years, the St. Gallen (SG) International Consensus Conference on the treatment of patients with primary breast cancer (SGBCC) has been taking place regularly. The SGBCC consensus is based on the majority vote of the SG panel and represents an international cross-section of opinions.RationaleThis article discusses and classifies the panel members' voting results for everyday clinical practice in Germany.BasisThe discussion is based on the German treatment recommendations of the 'Arbeitsgemeinschaft Gyn & auml;kologische Onkologie' (AGO Organkommission Mamma, Version 2025.1) which is updated every year, most recently in March 2025. The updated S3 guideline on 'Early detection, diagnosis, therapy and follow-up of breast cancer' was only available as a consultation version at the time.ResultsThis year's 19th SGBCC focused on practice-oriented issues related to early breast cancer, which-in part-were discussed and agreed upon using fictitious case studies with different variables. The rationale behind this was to address the increasingly personalized treatment decisions for early breast cancer. More than ever, not only tumor stage, tumor biology, breast cancer subtype, performance status, age or life expectancy are considered as individual factors, but also various molecular and genetic variables are part of the treatment decision-making process. The present manuscript is focusing on systemic tumor 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 .

Zusammenfassung Im Rahmen der COGNITION-Diagnostik-Studie wird verbleibendes Tumorgewebe nach neoadjuvanter Therapie (NAT) von Patient*innen mit Brustkrebs im Frühstadium (eBC), die nach NAT ein erhöhtes Rückfallrisiko haben, mithilfe von Next-Generation-Sequencing analysiert, um Biomarker sowie aktionsfähige genomische Alterationen zu identifizieren. Das Ziel ist eine Stratifizierung der Patient*innen für nachfolgende genomikgeleitete Therapien, um das erhebliche Risiko einer metastatischen Disseminierung zu reduzieren und dadurch das krankheitsfreie Überleben zu verbessern. COGNITION-GUIDE ist eine multizentrische, übergreifende Phase-II-Studie zur Umsetzung von molekularen Biomarker-Profilen, die mit der COGNITION-Plattform erstellt wurden, in 6 molekular geleitete post-neoadjuvante Therapie-Optionen, zusätzlich zur Standardbehandlung. Die Patient*innen werden einer Behandlung mit Der primäre Endpunkt der Studie ist das invasive krankheitsfreie Überleben (IDFS) 4 Jahre nach dem operativen Eingriff. Zu den sekundären Endpunkten gehören das IDFS – separat für jeden Studienarm –, das langfristige krankheitsfreie Überleben, das Gesamtüberleben und die Sicherheit. Über einen Zeitraum von 4 Jahren werden 240 Patient*innen in die Studie aufgenommen. Die im Juni 2023 aktivierte COGNITION-GUIDE-Studie wird bundesweit in verschiedenen Zentren Patient*innen rekrutieren. Die Studie soll die Grundlage für einen risikoadaptierten, biomarkergeleiteten Algorithmus zur Therapie-Eskalation bei eBC-Patient*innen mit einem hohen Metastasenrisiko schaffen.

Die Systemtherapie des Mammakarzinoms ist einem stetigen Wandel aufgrund der kontinuierlich erscheinenden neuen Studienergebnisse unterworfen. Dies verlangt daher die jährliche Überarbeitung der AGO(Arbeitsgemeinschaft Gynäkologische Onkologie)-Empfehlungen, um den neuen therapeutischen Entwicklungen Rechnung zu tragen. Beim frühen Mammakarzinom gilt es, eine Über-, aber auch Untertherapie zu vermeiden. Daher ist die Selektion einer risikoadaptierten Systemtherapie unter Berücksichtigung der tumorpathologischen Faktoren im interdisziplinären Tumorboard das primäre Ziel. Beim metastasierten Mammakarzinom steht im Vordergrund die Testung der für den Subtyp relevanten Biomarker bzw. der Nachweis therapierelevanter Mutationen (e.g. PIK3CA, ESR1) zur Selektion der geeigneten Therapie. Da oft mehrere Möglichkeiten zur Verfügung stehen, besteht derzeit die größte Herausforderung in der optimalen Sequenzierung der bestehenden Therapieoptionen. Dies gilt vor allem für das metastasierte HR(Hormonrezeptor)-positive Mammakarzinom.