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.

Introduction:Primary chemoradiotherapy is the established and standard treatment for locally advanced cervical cancer. The INTERLACE study investigated the impact of adding induction chemotherapy with six cycles of carboplatin AUC2 and paclitaxel 80 mg/m 2 weekly prior to chemoradiotherapy on recurrence-free and overall survival. However, adaptation with adoption into routine clinical practice in Germany has been rather cautious. Methods:Patients treated according to the INTERLACE scheme at the University Medical Center Hamburg-Eppendorf between October 2023 and December 2024 were evaluated and described. Results:Seven patients with advanced cervical cancer (ECOG 0-1, median age 37 years, 43% FIGO stage IB1/2) treated with the INTERLACE regimen were identified during the study period. All patients received six cycles of the planned induction chemotherapy. The median time between completion of chemotherapy and the start of radiotherapy was 10 days, with the total duration of treatment varying between 43 and 63 days. All patients were able to complete radiotherapy using tele- and brachytherapy. 43% received all 5-6 cycles of cisplatin, 86% received at least four cycles of cisplatin simultaneously with radiotherapy. There were various reasons for discontinuing concomitant chemotherapy (1 hematological, 3 non-hematological).

Zusammenfassung Der Fallbericht beschreibt den außergewöhnlichen Krankheitsverlauf einer 54-jährigen Patientin mit metastasiertem triple-negativem Mammakarzinom (TNBC) und Hirnmetastasen, die ein langfristiges Ansprechen auf Sacituzumab Govitecan (SG) zeigte. Nach Progression unter Standardtherapien, einschließlich Chemotherapie und Immuntherapie, erreichte sie unter SG über 53 Therapiezyklen eine stabile Erkrankungssituation und übertraf die üblicherweise schlechte Prognose dieser Hochrisikogruppe deutlich. Der multimodale Ansatz – bestehend aus chirurgischer Resektion, stereotaktischer Bestrahlung und systemischer SG-Therapie – ermöglichte eine Krankheitskontrolle über mehrere Jahre. Der Fall verdeutlicht das Potenzial von SG bei TNBC mit ZNS-Beteiligung und unterstreicht die Bedeutung weiterer Forschung zu ADCs und deren Integration in kombinierte Therapiestrategien.

Background Recent years have seen rapid advances in human epidermal growth factor receptor 2 (HER2)-directed therapies for breast cancer. The shifting therapeutic landscape has presented patients and clinicians with a plethora of effective treatment options, but optimal treatment sequencing can be challenging. Tucatinib is a HER2-selective tyrosine kinase inhibitor that, when given in combination with trastuzumab and capecitabine, has demonstrated survival benefits for patients with HER2-positive (HER2+) metastatic breast cancer (MBC) pretreated with trastuzumab, pertuzumab, and trastuzumab-emtansine. Real-world data, which can supplement knowledge gained from clinical trials, has begun to emerge for tucatinib, but a comprehensive review of these studies has yet to be conducted. Methods A systematic literature review was conducted to identify studies published between January 2020 and January 2025 that evaluated the effectiveness and safety of tucatinib in routine clinical practice. Studies were eligible for inclusion if they utilized real-world data, involved patients with HER2+ MBC treated with tucatinib in any line of metastatic therapy, and assessed tucatinib's effectiveness, health-related quality of life (QoL), patient-reported outcomes (PROs), or safety. Results Of 468 unique references identified, 12 publications met the inclusion criteria, 3 of which were manuscripts and 9 of which were congress abstracts. Included studies were heterogeneous in sample size, the lines of therapy assessed, and outcomes reported. Tucatinib-based treatment outcomes in the post-trastuzumab deruxtecan (T-DXd) setting and for patients with brain metastases were also reported. Despite variability among studies, outcomes were broadly consistent with clinical trial findings. Conclusion Overall, the available real-world evidence supports the clinical effectiveness of tucatinib-based therapies in HER2+ MBC, including heavily pretreated populations, patients with prior exposure to T-DXd, and those with brain metastases. However, gaps remain in the real-world data regarding the safety profile of tucatinib and its impact on health-related quality of life in routine clinical practice.

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.

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.

Das Hormonrezeptor-positive/HER2-negative Mammakarzinom ist die häufigste Mammakarzinomart. Trotz meist kurativer Erstbehandlung entwickeln bis zu 26

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).

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.

PurposeMutations in PIK3CA are one of several actionable mutations for patients with hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer. Alpelisib in combination with fulvestrant was the first approved PI3K inhibitor and was introduced in clinical practice in 2019. A lack of evidence for the use of alpelisib in the context of current treatment options like cyclin-dependent 4/6 inhibitor (CDK4/6i), highlights the importance of this analysis. We provide a real-world analysis of the use of alpelisib with the prospective German PRAEGNANT registry (NCT02338167).Methods57 patients with advanced breast cancer receiving alpelisib and fulvestrant were identified. 55 Patients had received prior CDK4/6i therapy. Progression-free survival (PFS) and overall survival (OS) were calculated for all patients, and stratified according CDK4/6i pre-treatment, using the Kaplan-Meier method. Subgroups (age, line of therapy, concomitant disease among others), somatic PIK3CA mutations, reasons for discontinuation and adverse events (AEs) were analyzed.ResultsThe median PFS was 5.0 (95% confidence interval [CI], 3.1-9.4) months, and the median OS was 20.1 (95% CI, 14.6-30.8) months. Line of therapy and concomitant diseases appeared to affect PFS, while the line of therapy and preexisting diabetes influenced OS. However, subgroups were too small for statistical testing. Discontinuation was mainly due to tumor progression (56.1%). Hyperglycemia, rash and diarrhea were the most documented AEs.ConclusionThis prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.

BACKGROUND:The surrogacy value of distant disease-free survival for overall survival has not been validated in neoadjuvant randomised controlled trials (RCTs) for early breast cancer. Here, we assess the trial-level surrogacy value of distant disease-free survival for overall survival. METHODS:In this pooled analysis, we included individual patient data from RCTs of neoadjuvant therapy for early breast cancer conducted by the German Breast Group (GBG) and the German Gynecological Oncology Breast Study Group (AGO-B) with available data on distant disease-free survival and overall survival. We used the trial-level measure of surrogacy R2trial from two-stage meta-analytical copula methods to quantify the association between treatment effects on overall survival and distant disease-free survival, overall and in prespecified clinical and pathological subgroups. According to ReSEEM guidelines, R2trial values of 0·7 or higher represent strong correlations, values between 0·69 and 0·5 represent moderate correlations, and values of less than 0·5 represent weak correlations. FINDINGS:11 RCTs, with a total of 15 neoadjuvant treatment comparisons and 12 247 patients, were included in the analysis. Overall, there was a strong association between copula model-based hazard ratios (HRs) for overall survival and copula model-based HRs for distant disease-free survival (R2trial=0·91 [95% CI 0·82-1·00]). No significant heterogeneity of results was observed across the majority of subgroups analysed (pheterogeneity>0·05 in all subgroups), with the exception of subgroups defined by tumour molecular features, such as tumour progesterone receptor status, HER2 status, and molecular subtypes. For molecular subtypes, the R2trial for the association between distant disease-free survival and overall survival was higher than 0·7, indicating strong surrogacy in hormone receptor-negative and HER2-negative tumours (R2trial=0·89 [95% CI 0·75-1·00]) and hormone receptor-negative and HER2-positive tumours (0·73 [0·36-1·00]), and below the 0·5 threshold for weak surrogacy in hormone receptor-positive and HER2-negative tumours (0·33 [0·00-0·83]) and hormone receptor-positive and HER2-positive tumours (0·11 [0·00-0·55]; pheterogeneity=0·021). INTERPRETATION:With adequate follow-up, distant disease-free survival is a robust surrogate endpoint for predicting final overall survival outcomes in neoadjuvant RCTs for early breast cancer in most contexts. However, the distant disease-free survival surrogacy appears to be weak for the hormone receptor-positive and HER2-negative and for the hormone receptor-positive and HER2-positive molecular subtypes. These latter findings warrant further investigation in more recent RCTs enrolling higher-risk patient populations. FUNDING:None.

Supplementary figure 2: Distribution of RAD51 and γH2AX continue values

Background:The development of brain metastases (BM) is an increasing concern for patients with metastatic triple-negative breast cancer (mTNBC). This systematic review aimed to summarize the current evidence regarding systemic treatment options for patients with mTNBC and BM. Methods:A systematic literature review was conducted by searching the database PubMed with the keywords metastatic triple-negative breast cancer," "therapy" and "brain metastases." Articles were screened and included if they focused on the treatment of mTNBC. Both prospective and retrospective clinical trials were eligible for inclusion. Results:The literature search identified 3,413 articles, of which eight met the inclusion criteria. These studies provided evidence for the treatment of patients with stable BM using sacituzumab govitecan, pembrolizumab combined with chemotherapy, trastuzumab deruxtecan (T-DXd), nab-paclitaxel combined with cisplatin, and talazoparib. No evidence was found for active BM or leptomeningeal metastases. Conclusion:Based on the current evidence discussed in this review, testing for programmed death-ligand 1 (PD-L1), HER2, including immunohistochemistry (IHC) status as well as germline BRCA 1/2 mutation, should be considered in all mTNBC patients with BM as the results have significant treatment implications. Moreover, PD-L1 expression should be evaluated on primary tumor and (if tissue sample available) reevaluated on BMs if negative on primary BC, to maximize the opportunity for treatment with immune checkpoint inhibitors. Furthermore, if brain tissue is available, HER2 IHC should also be tested in order to evaluate the status switch and to assess the therapeutic effectiveness of treatment with T-DXd. Further targeted agents are urgently needed in order to improve the survival of patients with TNBC and BM.

OBJECTIVE:Clinically significant existential distress may impair quality of life and communication about illness. We investigated the presence of existential distress in the form of demoralization, death anxiety, and dignity-related distress, and its co-occurrence with mental disorders in patients with advanced cancer. METHODS:We conducted structured clinical interviews and administered self-report questionnaires to assess existential distress and mental disorders. We recruited patients with different Union for International Cancer Control (UICC) stage IV solid tumors from in- and outpatient oncology and palliative care settings. RESULTS:A total of 671 patients completed assessments (55 % participation rate, 48 % female, primary tumor site: 28 % lung, 14 % prostate, 11 % breast). Clinically relevant levels of existential distress were present in 46.4 % (95 % CI, 41.7 % to 51.1 %), including demoralization, 12.5 % (95 % CI, 9.6 % to 15.9 %), death anxiety, 27.3 % (95 % CI, 23.2 % to 31.6 %), and dignity-related distress, 38.7 % (95 % CI, 34.2 % to 43.3 %). Frequent existential distress symptoms were sense of entrapment and fear of own and close others' suffering. Mental disorders occurred in 26.2 % (95 % CI, 22.2 % to 30.4 %), including major depression, 8.6 % (95 % CI, 6.2 % to 11.5 %), anxiety disorders, 8.4 % (95 % CI, 6.0 % to 11.3 %), and ICD-11-adjustment disorder, 10.5 % (95 % CI, 7.9 % to 13.7 %). Existential distress and mental disorders co-occurred in 20.0 % (95 % CI, 16.4 % to 24.0 %). CONCLUSION:Existential distress is a common, clinically significant problem in patients with advanced cancer. Its recognition in multiprofessional clinical settings can contribute to improve quality of life. Most patients with a mental disorder show comorbid existential distress requiring treatment of both.