Abstract In recent years, B cells and tertiary lymphoid structures (TLS) have emerged as key predictors of immunotherapy response across multiple cancers. B cells exist in various states of spatial organisation within the tumour microenvironment (TME), likely supporting many of their functional roles. However, the landscape of B cell spatial organisation in cancer, and specifically in triple-negative breast cancer (TNBC), is poorly characterised. Organisation and function are processes that are likely orchestrated by a diverse set of immune signalling, but the interplay between organisation and its underlying signalling remains largely uncharacterised in cancer, underscoring the need for a comprehensive and systematic investigation. To characterise the spatial landscape of B cells and immune signalling, we implemented a novel approach for the simultaneous detection of protein and RNA in situ using imaging mass cytometry. We applied this assay to a randomised immunotherapy clinical trial, NeoTRIP, where patients with TNBC were treated with neoadjuvant chemotherapy with or without atezolizumab. Samples were collected from 268 patients at three timepoints: baseline, on-treatment and post-treatment. This study identified that germinal centre B, B and plasma cell densities were significantly associated with response to immunotherapy on-treatment. We identified distinct B and plasma cell niches in TNBC, and showed that B activated niche cell densities were also strong predictors of response to immunotherapy. Additionally, we found that many B and plasma to TME interactions were enriched among immunotherapy responders. These findings were complemented by strong treatment-induced cellular dynamics. Strikingly, the most marked increase in TME cell phenotype abundance in immunotherapy responders was observed in B cells - particularly naïve B cells and broader B cell populations, suggesting that effective immunotherapy induces their expansion following treatment. We subsequently showed that cytokines likely behave in a spatially coordinated manner in the TME, being significantly enriched in the vicinity of the observed B and plasma cell niches. Cytokine expression mirrored the observed immune expansion on-treatment and was also associated with immunotherapy response. Specifically, cytokine-enriched niches appeared to be a feature of immunotherapy responders, suggesting that together organisation and signalling play a central role in treatment responses. Together, these findings highlight a previously unexplored diversity of B cell spatial organisation and its associated immune signalling in TNBC, suggesting that B cell features may serve as on-treatment predictors of immunotherapy response. Citation Format: Lubna Ahmad, Xiao Qian Wang, Neus Masqué-Soler, Ellen Schrader, Chiun-Sheng Huang, Daniel Egle, Maurizio Callari, Matteo Dugo, Begoña Bermejo, Claudio Zamagni, Marc Thill, Antonio Antón, Stefania Russo, Elena Sevillano, Eva Maria Ciruelos, Richard Greil, Balázs Győrffy, Vladimir Semiglazov, Marco Colleoni, Catherine M. Kelly, Lucia Del Mastro, Gabriella Mariani, Guiseppe Viale, Luca Gianni, Giampaolo Bianchini, Raza Ali. Mapping the spatial organisation of B cells and immune signalling in TNBC to characterise response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6752.

e12741 Background: Early-stage HER2-positive breast cancer represents a biologically aggressive subtype; however, outcomes have substantially improved with the introduction of HER2-targeted therapies. Anthracyclines have been considered a cornerstone of chemotherapy, but their role is increasingly being questioned. Recently, antibody–drug conjugates are being evaluated in clinical trials with the aim of redefining treatment standards in the early setting. However, some comparative concepts remain methodologically limited, particularly when anthracycline-based regimens are administered without concurrent HER2-targeted therapy and compared with modern regimens that include simultaneous HER2 blockade. From both a biological and clinical perspective, the concomitant administration of chemotherapy and HER2-directed treatment appears critical to maximize antitumor efficacy. Non-pegylated liposomal doxorubicin (Myocet) has been developed to reduce cardiotoxicity while preserving antitumor activity, offering a potential strategy for anthracycline-based approaches with an improved safety profile. Methods: We performed a retrospective analysis of 164 consecutive patients with early-stage HER2-positive breast cancer treated at the Department of Obstetrics and Gynecology, Medical University of Innsbruck between April 2013 and February 2022. Patients were routinely assigned to receive six cycles of a neoadjuvant regimen consisting of Myocet, docetaxel and dual HER2 blockade administered concurrently. Primary endpoint was pathological complete response (pCR) rates. Secondary endpoints included overall survival, disease free survival and cardiotoxicity. Results: A total of 164 patients were analyzed. Median follow-up was 8,38 years (Q1,Q3; 6,5, 10,08). The median age at diagnosis was 50,8 years (Q1, Q3; 42,7, 58,7). In our cohort, 56% of patients were pre- and 43% postmenopausal. Regarding hormone receptor (HR) status, 42% (69/164) were HR negative and 58% (95/164) HR positive. PCR rate was achieved in 81,1% (133/164) of patients. Patients exhibiting HR negative cancers showed pCR more often, 92,8% (64/69), compared to HR positive patients, 72,6% (69/95). Overall survival in our cohort was on median 90,4 months (Q1, Q3; 65,4, 110,2) and disease-free survival 83,2 months (Q1, Q3; 60, 106,5). Data regarding cardiotoxicity was available for 89% (146/164) of patients at the time of their operation and 90% (147/164) of patients at the end of their treatment. At both time points, two patients (1%; 2/146, 2/147) had a left ventricular dysfunction grade CTCAE 2 (LVEF 40-49% and LVEF reduction of > 10%). Conclusions: In our cohort providing real world data, simultaneous anthracycline-based chemotherapy and dual HER2 blockade in early-stage HER2-positive breast cancer was an effective treatment with a pCR rate of 81,1% and excellent cardiac safety.

BACKGROUND:Brain metastases (BM) cause substantial morbidity and reduced survival in metastatic breast cancer (MBC). Therapeutic advances may have altered BM incidence and outcomes across subtypes. Real-world data are crucial to assess these trends and guide BM-specific clinical trials. Here, we report BM data from the Austrian Study Group for Medical Tumor Therapy MBC registry. METHODS:Patients with known hormone receptor (HR) and HER2 status and sufficient outcome data were included. Logistic regression was used to assess the risk of BM. Overall survival (OS) was estimated using Kaplan-Meier methods and compared by log-rank tests. Multivariable Cox models with BM as a time-dependent variable and competing-risk analyses were applied. RESULTS:Among 2775 patients, 477 (17.2%) developed BM during the metastatic course; 56 patients (2.0%) had brain-only disease at first metastatic diagnosis. Compared with luminal MBC, BM risk was higher in HR-/HER2+ (OR 3.57), HR+/HER2+ (OR 4.43), and triple-negative breast cancer (TNBC; OR 2.91). At a median follow-up of 77 months, BM were associated with significantly shorter OS (HR 4.23; p < 0.001). TNBC showed the shortest BM-free survival (7.1 months) and poorest OS after BM diagnosis (4.7 months). Brain-only disease was associated with improved OS compared to concurrent extracranial disease (HR 0.58; p = 0.001). Use of whole brain radiotherapy declined over time, while neurosurgery or focal radiotherapy were associated with longer OS. Receptor discordance included HR loss (14.5%) and HER2 gain (9.8%). CONCLUSION:BM remain frequent and prognostically relevant in MBC, underscoring the need for improved risk stratification and subtype-specific therapies.

BACKGROUND:The aim of this study was to validate the Xpert Breast Cancer Insight (BC Insight) test. BC Insight is a multigene assay consisting of three target genes and three reference genes. MATERIALS AND METHODS:We studied the BC Insight test in 1278 formalin-fixed, paraffin-embedded surgical specimens from postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer with 0-3 involved lymph nodes. Time to distant recurrence (DR) and overall survival (OS) were analyzed using Cox models. RESULTS:The BC Insight test categorized 764 of 1089 (70.2%) evaluable patients as "low risk". The Xpert BC Insight Risk Score (XRS) was prognostic for DR (hazard ratio (HR) 1.93, 95% confidence interval (CI) 1.58 to 2.35, P<0.0001; C-index 0.73) and OS (HR 1.45, 95% CI 1.26 to 1.67, P<0.0001; C-index 0.65). At 10 years, 95.3% of Xpert BC Insight Risk Category (XRC) low-risk patients were metastasis-free and 89.6% were alive, compared with 85.6% and 77.1% of XRC high-risk patients, respectively (absolute DR risk difference 9.7%, P<0.0001; absolute risk of death difference 12.5%, P<0.0001). CONCLUSIONS:XRS and XRC are prognostic for DR in postmenopausal women with ER-positive, HER2-negative primary breast cancer. Furthermore, the BC Insight test accurately predicted OS in these patients, particularly in patients with 1-3 involved lymph nodes.

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer (eBC) represents the most common breast cancer subtype, with relevant recurrence risks despite optimal endocrine therapy (ET) and locoregional treatment. Long-term data from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) demonstrate that recurrence risk remains substantial, with outcomes strongly influenced by nodal burden, tumor size, and biological parameters. Advances in systemic therapy, including optimized endocrine strategies, chemotherapy, bone-modifying agents, PARP inhibitors for patients harboring germline BRCA 1/2-mutations, have significantly improved survival, yet recurrence remains a clinically relevant challenge, including for node-negative patients harboring additional biological risk features. The introduction of adjuvant CDK4/6 inhibitors represents an important therapeutic development. Abemaciclib (monarchE) has demonstrated sustained improvements in invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and a statistically significant overall survival (OS) benefit at 7 years. Ribociclib (NATALEE) demonstrated statistically significant IDFS improvement across a broader clinical risk spectrum, including selected node-negative disease. However, these advances must be considered in the context of distinct toxicity, treatment burden, and substantial additional healthcare system costs. Although emerging evidence supports treatment intensification with CDK4/6 inhibitors in certain settings, uncertainty persists regarding which patient subgroups derive sufficient benefit to justify routine use from both a clinical and health-economic perspective. Further clarification is expected from ongoing randomized studies and real-world evidence, as this paper aims to provide a structured, evidence-based overview of the current standard of knowledge and to support Austrian breast cancer specialists in navigating treatment decisions regarding adjuvant CDK4/6 inhibitor use.

Abstract Metastatic breast cancer is one of the leading causes of premature mortality among women worldwide. A major barrier to optimal care is the marked heterogeneity in both the temporal dynamics of metastatic spread and the organ-specific spatial distribution of metastases. Existing analyses do not adequately capture this complexity, as they either neglect temporal dependencies or assume independence between metastasic sites. As a result, it remains unclear how established metastases influence subsequent organ-specific dissemination. We address this question using patient-level longitudinal trajectories from a large multicentre real-world metastatic breast cancer registry, combined with an AI-assisted disease-progression modelling framework based on continuous-time Markov chains that represent combinations of metastatic sites and the non-uniform and practice-driven timing of radiologic response assessments, as encountered in routine clinical care. We present a stochastic model determined by progression rates, which are parameterised to capture baseline organ-specific transition risks, patient-level covariates, and pairwise inter-organ interaction effects. High-dimensional treatment information is incorporated using an large language model based encoding. We find that metastatic spread follows non-independent, subtype-specific spatiotemporal patterns, with subtype-specific inter-organ interaction patterns that shape progression. Visceral metastases, particularly lung and liver metastasis, are associated with an increased hazard of subsequent brain metastasis, with effects varying across hormone receptor-positive, HER2-positive, and triple-negative subtypes. Together, these findings define a clinically relevant spatiotemporal architecture of metastatic progression in breast cancer. This framework enables refined mechanism-informed risk stratification and provides a data-driven rationale for targeted and risk-adapted – rather than symptom-triggered – surveillance strategies.

This study evaluates the feasibility and technical success rate of real-time virtual sonography (RVS) for prone contrast-enhanced breast MRI sequences during second-look examinations. Usually, additional supine MRI sequences are acquired for coregistration. This single-center retrospective study was performed in a cohort of female patients who underwent contrast-enhanced prone breast MRI followed by second-look ultrasound for MRI-detected incidental lesions. RVS was used to coregister supine ultrasound and prone MRI data without requiring additional supine MRI studies. Lesion localization success, as well as lesion visibility, fusion quality, and histopathological correlation through ultrasound-guided biopsy, were assessed. A covariate analysis of factors affecting lesion localization was performed. A total of 103 female patients (mean age 48.3 ± 11.0 years) with 125 MRI-detected breast lesions were included. Of the lesions, 91.2

Using patient-reported outcomes (PROs) and more objective measures, we evaluated adherence to adjuvant palbociclib and ET in the PALLAS trial, and the impact of palbociclib on ET adherence. The open-label, global, phase 3 PALLAS trial randomized patients with hormone receptor-positive (HR+), HER2-negative stage II–III breast cancer (1:1) to either 26 cycles of palbociclib (125 mg/day for 21 days and then 7 days off) plus adjuvant ET, versus ET alone. After 23.7 months median follow-up, palbociclib was stopped due to futility of the intervention and patients were moved to follow-up. For each cycle, daily adherence to ET was measured with study diaries; for palbociclib, study diaries and pill counts. At cycles 2, 3, 6, 12, 18 and 24, patients completed the Morisky Medication Adherence Scale-4 plus an additional item and the McHorney Adherence Questionnaire. Mean persistence was defined in months from treatment initiation to cessation. Four thousand six hundred eighty-eight of 5796 total PALLAS participants were included. Across all cycles, mean daily ET adherence values measured by study diary were > 98.0

Background: Breast clip marker movement after ultrasound-guided biopsy can negatively affect lesion re-localisation rates and surgical outcomes, underscoring the need for improved understanding of the factors influencing clip displacement. Thus, this study aimed to compare four different breast clip markers and identify risk factors for clip migration and dislocation after ultrasound-guided placement. Methods: This retrospective study included 350 patients who underwent ultrasound-guided biopsy of a newly diagnosed breast lesion with placement of one of four types of breast clips (UltraClip Dual Trigger Biodur 108 Coil Marker [UC], TUMARK Professional [TP], TUMARK Vision [TV] and HydroMARK Breast Biopsy Site Marker [HM]). Clip migration and dislocation were assessed immediately after placement and during follow-up imaging for at least 3 months. A binary logistic regression analysis was performed to identify predictors of clip dislocation including lesional, perilesional and procedural parameters. Results: Clip migration rates were 26.0%, 18.0%, 10.0% and 25.0% and clip dislocation rates were 14.0%, 20.0%, 9.0% and 38.0% for UC, TP, TV and HM, respectively. Features significantly associated with clip dislocation included predominantly fatty surrounding tissue (p = 0.046) with low perilesional shear wave velocities (p = 0.054), smooth lesion contours (p = 0.041), soft lesion strain elastography (p =0.001), low clip-to-lesion-surface distance (p = 0.002) and the use of an HM breast clip (p = 0.032). Conclusions: The type of breast clip-marker, as well as perilesional and lesional characteristics, influence the likelihood of clip dislocation. Notably, the hydrogel-coated clip (HM) exhibited the highest rate of dislocation.

Background:Patients with osseous metastatic breast cancer receive bone-modifying agents (BMAs) as part of their standard care. Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of this class of drugs. MRONJ heavily impacts patients' quality of life and represents a major medical burden necessitating a discontinuation of treatment. Currently, the diagnosis of MRONJ is established upon the manifestation of clinical symptoms like exposed necrotic jawbone, pain, swelling or signs indicative of infection of the jaw. The objective of this study was to assess the potential of imaging modalities, specifically FDG-PET/CT (positron emission tomography with computed tomography) in the early detection of MRONJ. Methods:This cohort study in Austria included all patients with metastatic breast cancer who were receiving denosumab and regular PET/CTs, diagnosed with MRONJ between 2000 and 2022 at the Department of Obstetrics and Gynecology Innsbruck. For each of the patients in the study cohort, two control patients with comparable clinical characteristics were matched to serve as a control group. Control patients with metastasized breast cancer did not develop MRONJ but did receive denosumab and regular FDG-PET/CTs. Imaging data were independently assessed by two experienced nuclear medicine physicians. Findings:Baseline characteristics were well balanced. Patients received 120 mg denosumab once per month subcutaneously without de-escalation of therapy. The median time to develop MRONJ was 23 months (range 5-71, lower Quartile (Q1), upper Quartile (Q3) 16, 40 months). Nuclear medicine physicians detected jaw alterations in 91% (19/21) of MRONJ cases (sensitivity, 95% CI: 70%-98.8%) and in 29% (12/42) of controls, corresponding to a specificity of 71% (30/42; 95% CI: 55%-84%). Median lead time of imaging by demonstrating lesion in the jaw was 238 days (range 11-1118, Q1, Q3 106,494) prior to MRONJ diagnosis. In 68% (13/19) of MRONJ cases the nuclear medicine physicians were able to predict the exact tooth location of MRONJ with a deviation of no more than two teeth. Interpretation:The high sensitivity and negative predictive value of imaging for early detection of MRONJ underscore its significance for clinical practice. Given that the majority of patients receive regular PET/CTs, our results provide an excellent opportunity for early intervention when MRONJ is detected with a considerable lead time. Funding:This study received no external funding.

Circulating tumor DNA (ctDNA) is a promising biomarker in early breast cancer for assessing treatment response, minimal residual disease (MRD), and recurrence risk. In the ABCSG-34 phase II trial, we previously reported that persistent ctDNA during neoadjuvant therapy (NAT) was associated with higher residual cancer burden and lower rates of pathological complete response. Here, we present long-term follow-up data evaluating the prognostic relevance of ctDNA dynamics. ABCSG-34 randomized 400 patients to chemotherapy or endocrine therapy, with or without the MUC1 vaccine tecemotide. Tumor-informed SiMSen-Seq assays were used to assess ctDNA at baseline, mid-therapy, and end-of-therapy. Of 145 patients with ctDNA data, 109 had long-term follow-up (median: 7.1 years). Baseline ctDNA positivity was significantly associated with inferior overall survival (HR 2.12, p = 0.043) and shorter survival durations across all endpoints. Trends toward improved outcomes were observed in patients who cleared ctDNA during NAT, though statistical significance was not reached—likely due to limited sample size. These findings support baseline ctDNA as a prognostic marker in early breast cancer. While ctDNA clearance may reflect treatment efficacy, further validation in larger trials is needed. Ongoing studies will determine the role of ctDNA in guiding therapy and monitoring MRD.

Background: Novel neoadjuvant treatment options including combinations of chemotherapy with immune-checkpoint inhibitors have improved pathologic complete remission (pCR) rates and long-term outcomes in early-stage breast cancer. To better understand individual risk of relapse and stratify patients for post-neoadjuvant risk-adapted therapeutic interventions beyond the crude dichotomization of pCR, novel predictive factors serving as surrogate for immune-activation and long-term outcome are warranted. The interferon gamma signaling pathway is a key modulator of antitumor immune effects. In the present study, we assessed the role of PD-L1 and the interferon gamma related proteins STAT1 and IRF1 in different tissue compartments as prognostic and predictive biomarkers in the prospective randomized ABCSG 34 trial. Patients and Methods: In total, 289 tumor samples of 400 patients with early HR+/HER2- or TN breast cancer (BC) or triple-negative BC within the ABCSG 34 trial were available: 210 HR+/HER2 BC and 79 TN patients received neoadjuvant chemotherapy (anthracycline and taxane-based) and endocrine therapy, respectively. Patients were randomized 1:1 to receive either Standard of Care (SoC) or SoC plus the MUC1-based antitumor vaccine tecemotide. Expression of PD-L1 (Immune Score, IC: SP142 clone, Ventana and Combined Positivity Score, CPS: SP263 clone, Ventana), as well as STAT1 and IRF1 (both Cell Signaling Technology) expression at baseline, surgery (where available), and the change in expression during therapy was correlated with patient outcome. Also, STAT1 and IRF1 expression was determined in tumor cells, TILs and stromal fibroblasts. Expression levels were correlated with invasive disease-free (IDFS), distant relapse-free (DRFS) and overall survival (OS). Association with outcomes and use of tecemotide were estimated using univariable stratified (chemotherapy vs endocrine therapy cohort) Cox regression. For continuous markers the hazard ratios (HR) depict the change in hazards for an absolute 10%-point increase of the marker. Results: Higher PD-L1 IC in biopsy samples was associated with a better DRFS (HR 0.92, 95% CI 0.84 – 1; p = 0.048). In surgical specimens, a positive compared to a negative CPS was associated with improved DRFS (HR 0.31, 95% CI 0.10 – 0.99; p = 0.048). However, an increase in CPS during neoadjuvant therapy was associated with worse OS (HR 1.03, 95% CI 1 – 1.05; p = 0.032). Pre-therapeutic IRF1 expression in TILs was associated with a better IDFS (HR 0.64, 95% CI 0.42 – 0.98; p = 0.039) and DRFS (HR 0.55, 95% CI 0.34 – 0.88; p = 0.013). Post-therapeutic proportion of IRF1 expressing tumor cells was associated with a better DRFS (HR 0.62, 95% CI 0.42 – 0.92; p = 0.018). STAT1 expression in any of the compartments at any time did not show significant association with long-term outcome. These effects were independent of biological tumor subtype (HR+/HER2- or TNBC). No significant associations between the expression of the investigated biomarkers and any potential tecemotide benefit could be identified. Conclusion: The results of this study indicate that in the ABCSG 34 trial, PD-L1 positivity as determined by IC and CPS was able to predict better DRFS and OS. However, in patients with residual tumor, an increase in CPS during treatment was associated with decreased OS - a result that needs to be interpreted with caution, since no “post treatment sample” can be accessed in cases of pCR. In addition, IRF1 expression both in tumor cells and TILs predicted an improved IDFS and DRFS. STAT1 expression in any of the tissue compartments did not demonstrate significant association with survival. Despite a limited sample size, these results suggest that immune activation status of tumors and TILs as well as the microenvironment at the beginning of neoadjuvant treatment predict prolonged long-term outcomes, even when RCB/PCR rates remain unchanged. Citation Format: Ulrike M. Heber, Dominik Hlauschek, Christian F. Singer, Daniel Egle, Richard Greil, Ruth Helfgott, Gregor Huber, Elisabeth Müller-Holzner, Cornelia Hauser-Kronberger, Margaretha Rudas, Georg Pfeiler, Rupert Bartsch, Sigurd Lax, Martin Filipits, Gabriel Rinnerthaler, Michael Gnant, Zsuzsanna Bago-Horvath. Immune activation of tumor cells and microenvironment as assessed by PD-L1 expression and interferon gamma signaling predict long term disease-free and overall survival: Results of the prospective randomized neoadjuvant ABCSG 34 trial [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 P2-01-24.

Background: The synthetic lipopeptide tecemotide (liposomal BLP25, Stimuvax®) is an investigational cancer vaccine designed to induce a cellular immune response to cancer cells that express the glycoprotein MUC1. Aberrant MUC1 is widely over-expressed in malignancies such as lung, breast, and colorectal cancer. The aim of the prospective randomized two-arm multicenter phase-II ABCSG 34 trial was to investigate the efficacy and safety of tecemotide in 400 patients with early BC when given concomitantly with neoadjuvant systemic Standard-of-Care (SoC) chemotherapy or neo-endocrine therapy. The study was accompanied by an extensive translational program which included immune response parameters such as MUC1 and PD-L1 expression, TILs, monocyte and ctDNA. Patients and Methods: 400 patients with HER2- early BC were randomized 1:1 to receive neo-adjuvant SoC systemic therapy with or without 12 concomitant tecemotide vaccinations. Postmenopausal women with luminal A tumors received letrozole 2.5mg od for 24 weeks as SoC. TNBC patients and patients with luminal B tumors, in whom chemotherapy was considered to be SoC, received 4 x epirubicin/cyclophosphamide and 4 x docetaxel q3w. MUC1 protein expression on tumor cells was analyzed by immunohistochemistry. Invasive disease-free survival (IDFS), distant recurrence free survival (DRFS) and overall survival (OS) were analyzed with Cox regression models. Results: Seven years after surgery, follow-up (FU) data were collected retrospectively and available for 289 women. Of these, 236 had received chemotherapy, while 53 had received neo-endocrine letrozole. 141 had been randomized to receive concomitant tecemotide, while 148 had been randomized to SoC only. Patient and tumor characteristics in the FU group were highly representative of the overall study population, and clinical-pathological characteristics in the two randomization arms were well balanced. After a 7 year FU, patients who had received SoC + tecemotide had an IDFS of 69.1% vs 60.5% in the SoC alone group (HR 0.75, 95% CI 0.51–1.10, p=0.141). DRFS of patients who had received SoC + tecemotide was 80.8% vs 64.7% (HR 0.53, 95% CI 0.34-0.83, p=0.005); OS in the SoC + tecemotide was 83.0% vs 68.2% (HR for OS 0.53, 95% CI 0.33-0.85, p=0.008). Participants who had received chemotherapy + tecemotide had a particularly favorable outcome with an IDFS of 71.3% vs 59.8% (HR 0.69, 95% CI 0.45–1.05, p=0.084), a DRFS of 81.9% vs 65.0% (HR 0.50, 95% CI 0.31–0.83, p=0.007), and an OS of 83.6% vs 67.8% (HR 0.51, 95% CI 0.30–0.88, p=0.016). Sensitivity analysis adjusting for T-stage, Nodal status, KI67, cancer type, and age at randomization were consistent with the primary results and confirmed the robustness of the analysis. MUC1 protein data were available for 278 pts at baseline and 199 pts at surgery. MUC1 was expressed in 97.9% of baseline samples and in 98.5% of the surgical samples in which pCR was not achieved. Expression was high (i.e. detected in >80% of tumor cells) in 72.1% and 74.5%, respectively. While MUC1 expression levels were neither prognostic nor associated with pCR, tecemotide-treated patients with high MUC1 protein expression in their surgical sample showed a particularly good outcome with an improved IDFS (HR 0.57, 95% CI 0.34–0.98), DRFS (HR 0.38, 95% CI 0.20-0.72), and OS (HR 0.35, 0.17–0.71), when compared to SoC alone. Subgroup analysis and additional biomarker analyses will be presented at the meeting. Conclusions: Tecemotide, when given concomitantly with neoadjuvant SoC systemic therapy, profoundly improved IDFS, DRFS and OS in a follow-up analysis of this prospective Phase II trial. The improved long-term outcome was particularly evident in patients whose tumors expressed high levels of MUC1. While long-term outcome is an exploratory objective, this is the first study in which a therapeutic cancer vaccine has resulted in a statistically significant and substantial long-term survival benefit in breast cancer patients. Citation Format: Christian F. Singer, Dominik Hlauschek, Georg Pfeiler, Daniel Egle, Rupert Bartsch, Christoph Suppan, Angelika Pichler, Edgar Petru, Richard Greil, Margaretha Rudas, Michael Seifert, Gregor Huber, Andreas Petzer, Florian Fitzal, Zsuzsanna Bago-Horvath, Martin Filipits, Lidija Soelkner, Christian Fesl, Michael Gnant. Vaccination with MUC-1-targeting tecemotide improves Survival of patients receiving neo-adjuvant chemotherapy for early breast cancer: Results from the Prospective Randomized ABCSG 34 Trial [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 PS3-03.

510 Background: Carboplatin-based regimen are effective in patients (pts) with eTNBC, and olaparib improves the outcome of pts with BRCA1/2 pathogenic variants (PV), but the safety / efficacy of OC co-treatment in HRD-positive TNBC is unknown. ABCSG 45 (EU CT 2024-512821-10) is a prospective multicenter phase II study investigating the efficacy and tolerability of OC compared to conventional chemotherapy in HRD-positive eTNBC. Methods: Pts with HRD (Myriad genetics)-positive eTNBC were randomized to 6 cycles of olaparib (100 mg bid, days 4-16) / carboplatin (AUC 5) q3w, or 6 cycles of docetaxel/epirubicin/cyclophosphamide (75/50/500) q3w (TAC). In an initial dose-finding phase, 100 mg bid was identified as olaparib combination dose. Stratification factors were tumoral BRCA1/2 and menopausal status. Primary endpoint was centrally assessed residual cancer burden (RCB), pCR and QoL were secondary endpoints. Planned sample size was 90 pts, randomized 1:1 to achieve 80% power (two-sided alpha=0.05) to detect a RCB 0/I difference of 31%. Differences between treatment arms were assessed with a two-sided Cochran Mantel-Haenszel test using stratification factors. Pre-defined subgroup analysis was performed with logistic regression. Results: A total of 90 pts (OC: n=46; TAC: n=44), of whom 42 (47%) were BRCA1/2 PV carriers, were randomized between November 2019 and December 2023. Median age was 50.5 years (range 27.0-80.0). 40% had cT1, 55.6% cT2, and 4.4% cT3/4 tumors, and 60% of pts were clinically N0. 94.4% of tumors were G3, and Ki67 was >60% in 71.1%. Overall, the RCB0/I rate with OC was 52.2% vs. 70.5% with TAC (stratified risk difference = -18.8% (95%CI: -39.6% to 2.0%); p=0.068). In pts with BRCA1/2 PV, RCB0/I rates were comparable: 77.3% (OC) vs. 65.0% (TAC), while in 47 pts with BRCA1/2 wild type (WT), OC was significantly less effective: RCB0/I of 29.2% vs 73.9% in TAC (interaction p=0.008). pCR was achieved in 47.8% (OC) vs 59.1% (TAC; p=0.231). In pts with a BRCA1/2 PV, OC resulted in 77.3% pCR rate, vs. TAC 65.0%, in BRCA1/2 WT pts pCR was achieved by 20.8% (OC) vs. 56.5% (TAC) (interaction p=0.021). OC treatment resulted in more ≥ grade 3 hematologic toxicities with 30% vs 3% thrombocytopenia and 43% vs 18% neutropenia but caused fewer non-hematological toxicities. Conclusions: In this prospective randomized study in HRD-positive TNBC, 6 cycles of TAC resulted in strikingly high RCB0/I and pCR rates, independent of BRCA1/2 status. 6 cycles of OC achieved a pCR rate of >77% in BRCA1/2 PV but were less effective in pts with BRCA1/2 WT disease. These results may help to optimize neoadjuvant treatment strategies in TNBC. This research was conducted with support from AstraZeneca Austria GmbH. Clinical trial information: 2024-512821-10 .

Background: In early-stage breast cancer with initially positive axillary lymph nodes, reliable assessment of the involvement of the axilla is important because of the prognostic importance of lymph node metastases. After neoadjuvant chemotherapy (NACT), targeted axillary dissection (TAD), including sentinel lymph node biopsy and primarily involved lymph nodes, is currently regarded as the standard of care. The target lymph node must be marked using a clip/marker and later localized using a reliable guidance technique to identify the node, to avoid the indication of axillary lymph node dissection. Methods: The present study aimed to evaluate retrospective data collected from April 25, 2022, until March 30, 2023, on a consecutive series of patients, to determine the efficacy and safety of using the Sirius Pintuition GPSDetect™ surgical marker navigation system. Results: This consecutive case series shows that identification of the target node with surgical marker navigation is feasible and safe, with a 100% identification rate at surgery, in a population of 20 patients with histologically verified axillary lymph node involvement before NACT. Conclusion: Magnetically guided localization systems may therefore be a valid alternative to ultrasound-guided wire placement. The data highlight the practicality of the magnetically guided approach, which potentially contributes to a reduction in treatment-related morbidity by avoiding unnecessary axillary lymph node dissection.

Ultrasound is a highly effective imaging tool for assessing abnormalities within the breast. However, especially the identification of malignant tumors of the breast mimicking fibroadenomas (MTMF) by means of breast ultrasound can be challenging. This study aimed to identify reliable imaging characteristics of MTMF.This retrospective study was approved by the local ethics review board. After screening 623 patients, 421 cases with histologically verified fibroadenomas and MTMF between 2011 and 2021 were included. Sonographic features were compared to histopathological results and an algorithm-based quantitative ranking of predictors contributing most to the correct classification of malignant tumors was conducted.A total of 363 benign, 18 intermediate, and 40 malignant lesions were analyzed. Algorithm-based quantitative ranking showed that the most predictive features indicating malignancy were a hyperechoic rim (gain ratio merit 0.135 ± 0.004), an irregular border (0.057 ± 0.002), perilesional stiffening (0.054 ± 0.002), pectoral contact (0.051 ± 0.003), an irregular shape (0.029 ± 0.001), and irregular vasculature (0.027 ± 0.002).Ultrasound findings for fibroadenomas vary, making identification of MTMF challenging. Features such as indistinct margins and increased perilesional echogenicity are predictors for malignancy and should be considered during sonographic evaluation of fibroadenomas and MTMF.