BACKGROUND:Patients with breast cancer undergoing neoadjuvant chemotherapy mostly show insufficient therapy response and would highly benefit from an early prediction of pathological complete response (pCR). As vessels play a major role in drug delivery, ultrasound localisation microscopy (ULM) holds great promise as predictive tool by visualising vascular networks in high detail, at a resolution beyond the acoustic diffraction limit. METHODS:In this prospective pilot study (NCT05445050), we examined patients with breast cancer undergoing neoadjuvant chemotherapy using a ULM algorithm designed for conventional clinical ultrasound systems. To generate a vascular fingerprint, we performed the most detailed radiomics ULM analysis to date, based on longitudinal data from 20 patients. Features were used to classify therapy response using logistic regression and the performance of ULM was compared to clinically available imaging methods. FINDINGS:Compared to patients with non-pCR (n = 12), patients with pCR (n = 8) showed a more pronounced vascular network before therapy. Furthermore, their vessel coverage strongly changed following the first chemotherapy administration (26.97 [20.23-36.24] % vs. 6.00 [2.73-10.49] %), representing a promising biomarker for therapy prediction (p < 0.01, effect size: 2.21). ULM features allowed to correctly predict up to 85% (AUC: 0.85) of patient responses and already 75% (AUC: 0.73) before the start of therapy, thus outperforming tumour size measurements (accuracy up to 60%, AUC up to 0.53), B-mode images (accuracy up to 75%, AUC up to 0.76), maximum intensity projections of contrast-enhanced ultrasound (accuracy up to 75%; AUC up to 0.79), and histological CD31 staining (accuracy: 75%; AUC: 0.83). INTERPRETATION:Our findings emphasise the importance of vascular assessment in predicting pCR in patients with breast cancer and promote the translation of ULM as powerful clinical tool with the potential to optimise neoadjuvant treatment schedules. FUNDING:This work was supported by the German Research Foundation.

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.

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.

Background: Adenomyosis remains difficult to diagnose non-invasively due to clinical overlap with endometriosis and the limited specificity of imaging techniques. This pilot study evaluated whether serum- and urine-derived microRNA (miRNA) profiles, combined with machine-learning approaches, could support non-invasive diagnosis. Methods: Serum and urine samples were collected from 59 patients undergoing surgery for chronic pelvic pain at the Endometriosis Centre of RWTH Aachen University Hospital. Seven patients had isolated adenomyosis, 34 had histologically confirmed endometriosis, and 18 served as negative controls. miRNAs were profiled using next-generation sequencing. A structured feature-selection pipeline (variance filtering, univariate testing, mutual information, recursive feature elimination) was applied before training Logistic Regression, Random Forest, Support Vector Machine, and Decision Tree models using cross-validation. Model performance was evaluated using accuracy, precision, recall, F1 score, and ROC-AUC. Results: Distinct miRNA signatures were detected in both serum and urine, with urine-based models showing superior discriminatory performance. Logistic Regression and Support Vector Machine achieved excellent separation in urine datasets, although perfect AUC values must be interpreted cautiously due to the small number of adenomyosis cases. In serum, Random Forest achieved the highest AUC values (up to 0.98). Several miRNAs, including miR-183-3p, miR-320d-2, and miR-17, emerged as promising candidate biomarkers for differentiating adenomyosis from endometriosis and from negative controls. Conclusions: This pilot study demonstrates the feasibility of liquid-biopsy miRNA profiling combined with machine learning for non-invasive adenomyosis detection. Although results are preliminary and require validation in larger cohorts, urine miRNA profiles may represent a promising complementary tool to improve diagnostic accuracy and reduce diagnostic delay.

G7 trial design; demographics; tissue types; gene names; displayed data from additional analyses; statistical data

PURPOSE To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC). METHODS Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination R 2 from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points. RESULTS Eleven RCTs, for a total of 15 treatment comparisons and 12,247 patients, were included in the analysis. There was a weak association between hazard ratios (HRs) for OS and odds ratio of pCR overall ( R 2 , 0.07; 95% CI, 0.00 to 0.48), as well as in all the subgroups explored. Overall, the R 2 for the association between HR OS and HR iDFS was 0.46 (95% CI, 0.08 to 0.71), which is just below the cutoff of 0.5 for moderate surrogacy. In the majority of subgroups explored, the R 2 ranged from 0.5 to <0.7, while in hormone receptor–/human epidermal growth factor receptor 2– subtype, histologic grade 1-2 tumors, and lobular tumors, surrogacy was strong (ie, R 2 ≥0.7). The surrogacy value of iDFS for OS was affected by follow-up (FUP) length: R 2 substantially increased up to 36 months of FUP, with little further improvement after 48 months of FUP. CONCLUSION iDFS with sufficient FUP is an acceptable surrogate end point to confidently anticipate final OS results of neoadjuvant RCTs for early BC. This recommendation holds true across many subgroups, with the notable exception of HR+ disease. There is definite need to reassess whether OS is the optimal end point for treatment efficacy measurement in HR+ early BC.

Objectives: Adjuvant endocrine treatment for premenopausal patients with early hormone receptor positive HER2 negative (HRpos/HER2neg) breast cancer (BC) is supposed to depend on the estimated risk profile. Patients with a high recurrence risk should be offered aromatase inihibtors (AI) and ovarian function suppression (OFS) and patients with a low recurrence risk tamoxifen (TAM) with or without OFS. However utilization of these treatment options is diverse even in high risk patients. Aim of this retrospective study was therefore to assess the treatment patterns and outcomes of endocrine treatment variability in a real world setting. Methods: CLEAR-B is an anonymized retrospective study that uses prospectively collected data generated in the course of the certification process of breast centers in the period from January 2016 to June 1019 and from January 2022 to December 2023. Eligible were premenopausal patients with early HRpos/HER2neg BC an intermediate high and very high recurrence risk. Patient and disease characteristics are documented along with information about recommended and performed adjvuant treatments as well as information about recurrence and death. Results: The first patient was documented in February 2023. A total of 3.000 patients will be documented until August 2024 at 75 study sites in Germany. An interim analysis showed that the majority of documented patients is treated with tamoxifen despite an increased recurrence risk. Changes in therapy patterns and patient/disease characteristics will be analyzed according to patient risk profiles and in the two assessment periods (2016-2019 vs. 2022-2023). Additionally the context of healthcare provision (treatment centers vs. de-central healthcare) will be investigated. Summary: Awareness of treatment standards along with efficacy data and quality of life data is important to make informed therapy decisions about adjuvant endocrine treatment together with the patients. A full analysis of treatment patterns over time and outcomes will be presented at the conference. Citation Format: Bahriye Aktas, Hanna Huebner, Andreas Hartkopf, Maggie Banys-Paluchowski, Ingolf Juhasz-Böss, Nadia Harbeck, Hans-Christian Kolberg, Elmar Stickeler, Marcus Schmidt, Marc Thill, Michael Untch, Thorsten Kühn, Nina Ditsch, Lothar Häberle, Manuel Hoerner, Daniel Anetsberger, Kathrin Nicole Truch, Christian Roos, Christian Mann, Erik Belleville, Tanja Fehm, Peter A. Fasching. CLEAR-B - Adjuvant therapy effectiveness in patients with primary breast cancer: A retrospective registry study [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 P4-11-12.

Background/Objectives: Endometriosis is a chronic gynecological disorder characterized by ectopic endometrial-like tissue. The symptoms of this disease negatively affect the patient’s quality of life, both physically and mentally. This study aims to identify key factors impacting health-related quality of life in endometriosis patients. Methods: A total of 175 patients from the Endometriosis Centre of the RWTH Aachen University Hospital were assessed using the German version of the EHP-30. The EHP is a patient self-report tool used to measure the wide range of impacts that endometriosis can have on women’s lives (affecting pain levels, leading to feelings of powerlessness and a loss of control, and affecting their emotional well-being, social support, and self-image). Multivariate linear regression and random forest analyses were performed to evaluate predictors of health-related quality of life, focusing on demographic characteristics, pain severity, endometriosis symptoms and planned procedures. Results: Key factors that have a significant negative impact on QoL include higher pain scores, dysuria, and persistent endometriosis. Higher pain scores negatively affect the EHP-30 pain (p < 0.0001), control and powerlessness (p < 0.0001) and emotional well-being (p < 0.01) scores. Dysuria has a negative effect on pain (p < 0.001), control and powerlessness (p < 0.001), emotional well-being (p < 0.05), and social support (p < 0.05). Persistent endometriosis was negatively associated with pain (p < 0.01), control and powerlessness (p < 0.01), and social support. Previous endometriosis surgery has a positive effect on the EHP-30 scores for pain, control and powerlessness, emotional well-being, and self-image (p < 0.05). Conclusions: Our study highlights the multifactorial impact of endometriosis on health-related QoL. Personalized treatments focusing on pain management, emotional support and social interventions are crucial to improve patient outcomes.

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

Abstract Purpose: The randomized GeparOLA trial reported comparable pathologic complete response (pCR) rates with neoadjuvant treatment containing olaparib versus carboplatin. In this study, we evaluate the association between functional homologous recombination deficiency (HRD) by RAD51 foci and pCR and the potential of improving patient selection by combining RAD51 and stromal tumor-infiltrating lymphocytes. Patients and Methods: This is a post hoc blinded biomarker analysis from the randomized GeparOLA trial. Patients with early-stage HER2-negative breast cancer and HRD assessed by Myriad MyChoice or BRCA1/BRCA2 mutations were randomized 1:1 to receive (i) paclitaxel plus olaparib or (ii) paclitaxel plus carboplatin, both followed by epirubicin/cyclophosphamide. Functional HRD was predefined as a RAD51 score ≤10% (RAD51-low). Results: Overall, 90 of 97 (92.8%) samples were evaluable for RAD51 testing, and 72 of 90 (80.0%) were RAD51-low. The pCR rate in patients with RAD51-low tumors was 66.7% (48/72), whereas it decreased to 22.2% (4/18) in those with RAD51-high. In the multivariable model including clinicopathologic factors and treatment, the RAD51 score remained significantly associated with pCR (OR = 12.03; 95% confidence interval, 2.60–55.73; P = 0.002). Patients with RAD51-low and high stromal tumor-infiltrating lymphocytes in their tumors achieved a pCR rate of 75.0% (27/36). Similar results were observed for olaparib or carboplatin. In the exploratory disease-free survival analysis, no differences were observed between RAD51 groups (high vs. low: HR = 0.85; 95% confidence interval, 0.25–2.97). Conclusions: In a preselected population with HRD, according to a genetic test, RAD51 testing identifies patients with different pCR rates under PARP inhibitor-based or platinum-based therapies. Future biomarker-driven studies should consider this information to refine stratification factors and to improve patient selection.

Supplementary Figure S2. CAV1 and CAV2 expression in breast cancer.

Objectives: Transobturator tape (TOT) procedures are a widely used and effective treatment for stress urinary incontinence (SUI), but there is limited research on mesh-related complications and revision surgeries. This study aimed to evaluate the incidence of revision surgeries and mesh-related complications following TOT procedures and identify potential risk factors influencing these outcomes. Methods: This retrospective study analyzed data from patients who underwent TOT procedures at the specialized incontinence center of University Hospital Aachen (UHA), Germany, between January 2010 and May 2023. Patients were divided into three groups: initial surgery without revision, initial surgery with revision, and external referrals requiring revision. Statistical analyses included multivariate logistic regression and predictive cross-validation to identify risk factors for revision and mesh-related complications. Results: Out of 265 TOT procedures performed, the revision rate was 8.7%, and the mesh-related complication rate was 2.6%. Mesh complications, including erosion and wound dehiscence, accounted for 30% of revisions, while 70% of revisions were caused by recurrent stress urinary incontinence (SUI). External referrals showed longer revision intervals compared to UHA patients (53 months vs. 5 months; p = 0.003). Multivariate analysis identified rectoceles as a protective factor against revisions (p = 0.0414), while pre-existing conditions significantly increased revision risk (p = 0.0100). Conclusions: The revision rate following TOT procedures was 8.7%, with mesh-related complications accounting for 2.6%. Pre-existing conditions significantly increased the risk of revision, while rectoceles were associated with improved outcomes. These findings emphasize the importance of identifying patient-specific risk factors to enhance the safety and success of TOT procedures.

Background: Preoperative radiotherapy is a well-established treatment for various tumor types (rectal cancer, sarcoma, bronchial carcinoma). Promising studies on preoperative radiotherapy also exist for breast cancer, but most of them were not randomized or very old. Recent studies suggest that preoperative radiotherapy followed by immediate reconstruction or flap reconstruction is a low-complication method. There is evidence that the immunogenic effects of radiotherapy may lead to improved immune recognition of tumor cells. These potential immunogenic effects make preoperative radiotherapy a promising modality in interdisciplinary cancer therapy. In addition, preoperative radiotherapy may obviate the need to irradiate implants, expanders, or autologous transplants. NeoRad (NCT04261244, GBG116) is a multicenter, prospective, international randomized Phase III trial. It aims to investigate whether pre- versus postoperative radiotherapy after neoadjuvant chemotherapy (NACT) improves disease-free survival in patients with high-risk breast cancer and show superiority of preoperative radiotherapy (PRT) of the experimental treatment schedule in terms of disease-free survival (DFS). In addition, several secondary endpoints (cosmetic outcomes, quality of life, overall survival, etc.) will be assessed to better understand the benefits and risks of preoperative radiotherapy compared to the current standard of care. Study Design: Only patients with high-risk breast cancer who are eligible for NACT will be enrolled and randomly assigned in a 1:1 ratio to two study arms. In the standard arm, patients will undergo surgery, sentinel lymph node biopsy, possibly axillary dissection or targeted axillary dissection according to current S3/AGO guidelines. After surgery, patients will receive adjuvant radiotherapy +/- lymphatic pathways and, if indicated, systemic treatment according to S3/AGO guidelines. In the experimental arm, patients will receive whole-breast irradiation (WBRT) +/- lymphatic pathway irradiation after NACT. Approximately 3-6 weeks after radiotherapy, patients will undergo surgery including sentinel lymph node biopsy or axillary dissection, followed, if indicated, by post-neoadjuvant systemic therapy according to S3/AGO guidelines. Enrolment in post-neoadjuvant studies is allowed. To assess the response to NACT before radiotherapy, a biopsy of the primary tumor and suspicious lymph nodes is recommended in the experimental arm. An interim analysis on wound healing will be conducted after 100 patients have received breast-conserving surgery or autologous flap reconstruction (in both arms combined) and after 40 and 100 patients have been reconstructed with an implant (also combined from both arms). The recruitment period will be four years. The total study duration, including follow-ups, is ten years. Recruitment: The first patients were enrolled in 02/24 at the University Hospital of Düsseldorf. A total of 1826 patients will be recruited across 40 centers within 4 years. Funding: This study was supported by a grant from Deutsche Krebshilfe. Citation Format: Christiane Matuschek, Tanja Fehm, Maria Hufnagel, Vesna Bjelic-Radisic, Michael Untch, Michael Golatta, Danny Jazmati, Thorsten Kühn, David Krug, Jens Blohmer, Carsten Denkert, Beyhan Ataseven, Carolin Nestle-Krämling, Stefanie Corradini, Jens Huober, Jens Huober, Eugen Ruckhaeberle, Andreas Hartkopf, Theresa Link, Kerstin Rhiem, Elmar Stickeler, Claus Hanusch, Jörg Heil, Christine Solbach, Mattea Reinisch, Inga Bekes, Johannes Holtschmidt, Valentina Nekljudova, Sibylle Loibl, Wilfried Budach. Preoperative radiotherapy versus postoperative radiotherapy after neoadjuvant chemotherapy in high-risk breast cancer: a prospective, randomized, international multicentre Phase III trial—NeoRad [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 P3-10-22.

The use of CDK4/6 inhibitors, the new PI3K/AKT-kinase inhibitors, selective estrogen receptor-degraders (SERDs), antibody-drug conjugates, immune therapies and PARP inhibitors in recent years has resulted in a marked change in the therapy landscape for patients with advanced stage breast cancer. CDK4/6 inhibitors, trastuzumab deruxtecan, and sacituzumab govitecan have all been shown to provide significant overall survival benefits compared to conventional chemotherapy. Other substances are also showing promising results and hold out the hope that further analysis of the overall survival benefits will be available in the near future. The speed at which studies are now being carried out has markedly increased, and conferences and specialist journals are now constant sources of new information. This review summarizes the most recent publications and conference presentations on the treatment of patients with advanced stage breast cancer.