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The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na + /K + ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na + /K + ATPase inhibitor digoxin could reduce mean CTC cluster size. An analysis of nine patients treated daily with a maintenance digoxin dose (0.7-1.4 ng ml -1 serum level) revealed a mean cluster size reduction of -2.2 cells per cluster upon treatment (P = 0.003), meeting the primary endpoint of the study. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell-cell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Thus, our data provide a first-in-human proof of principle that digoxin treatment leads to a partial CTC cluster dissolution, encouraging larger follow-up studies with refined Na + /K + ATPase inhibitors and that include clinical outcome endpoints. ClinicalTrials.gov identifier: NCT03928210 ., Competing Interests: Competing interests: N.A. is a co-founder and member of the board of PAGE Therapeutics AG, Switzerland, listed as an inventor in patent applications related to CTCs, a paid consultant for companies with an interest in liquid biopsies, and a Novartis shareholder. C.R. is a co-founder of PAGE Therapeutics AG, Switzerland. The other authors declare no competing interests., (© 2025. The Author(s).)

Endometriosis is a disease affecting approximately 10% of reproductive age women. Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) occurs in some endometriosis cases. Histone deacetylase 6 (HDAC-6) is an enzyme with implication in several diseases including different cancer types and immunological disorders, where it is involved in protein trafficking and degradation, cell shape, and migration. In ARID1A-deficient ovarian cancer increased HDAC-6 expression lead to apoptosis-inhibiting post-translational modification of p53. It is not known if HDAC-6 expression is also altered in ARID1A-deficient endometriosis. The aim of this study was to assess HDAC-6 expression in endometriotic lesions in correlation to ARID1A-status. Two tissue-microarrays with 168 endometriotic lesions, including ovarian (64/168, 38 %), peritoneal (66/168, 39 %) and deep-infiltrating (38/168, 23 %) subtypes, and 73 endometrium of women without endometriosis were assessed. Mean ARID1A immunoreactivity score (IRS) in endometriosis group was 10.83 (±2.36) and 10.78 (±1.94) in the epithelium and stroma, respectively, while the respective mean HDAC6 IRS were 9.16 (±2.76) and 5.94 (±2.88). The comparison of the HDAC6 expression between endometriosis subtypes showed higher expression in deep-infiltrating endometriosis, in both, epithelium (p = 0.032) and stroma (p = 0.007). In ARID1A negative cases, epithelial expression of HDAC6 was higher in endometriosis compared to women without endometriosis (p = 0.031), and this was also specifically observed in the subset of ovarian endometriosis (p = 0.037). There were no significant differences in the stromal expression of HDAC6. In conclusion, our results demonstrate a complex expression pattern of HDAC6 depending on ARID1A status in different endometriosis subtypes. Further studies on HDAC6 and ARID1A are important to elucidate mechanisms involved in malignant transformation of endometriosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: We developed the online-based counseling tool iKNOW for women with a pathogenic germline variant in BRCA1/2 to improve risk understanding and quality of life., Methods: With a randomized controlled trial, we investigated the efficacy of iKNOW with regard to risk understanding (primary endpoint), quality of life, risk perception, and anxiety (secondary endpoints). Self-report questionnaires were administered to N  = 217 women with a pathogenic variant in BRCA1/2 before counseling (T0), immediately after (T1), 4 weeks after (T2), and 6 months after (T3)., Result: Deviations between self-assessed and calculated cancer risks tended to be smaller in the intervention group than in the control group but no longer significantly after adjustment for multiple testing. In the intervention group, the proportion of women with a correct understanding of breast cancer risk at T3 was higher (30.7% vs 14.7%; P  = .032). There were no differences in secondary endpoints., Conclusion: iKNOW tends to positively influence the understanding of familial cancer risk. At the same time, it does not negatively influence any of the secondary endpoints. However, converging evidence suggests that iKNOW seems to affect the quality of counseling processes and can thus be used as a paradigm for reinventing the notion of efficient, digital care., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)

Introduction: The subject of this guideline from the Institute of Family Medicine at the University of Zurich (IHAMZ) is the management of venous thrombosis. The review summarizes the current evidence and recommendations from international guidelines (1-6). The IHAMZ-guidelines focus on primary care, they also provide guidance on the coordination of general and specialist medical care as well as on the transition between outpatient and hospital care taking into account the special features of the Swiss healthcare system. The guideline is devided in two parts. Part 1 discusses the diagnosis and treatment of deep vein thrombosis (DVT). A validated algorithm is recommended for the diagnostic process, which begins with the assessment of the clinical probability. With the inclusion of the D-dimer test, the need for subsequent imaging diagnostics can be reduced. The differences between the evaluation of an initial and recurrent DVT are shown and the indications and scope of evidence-based environmental diagnostics (thrombophilia and tumor search) are presented. All patients with DVT should receive anticoagulation (AC) for 3-6 months, as there is a high risk of recurrence with AC 3 months. The duration of the subsequent secondary prophylaxis depends on the presumed risk of recurrence on the one hand and the risk of bleeding on the other. Part 2 is dedicated to special thrombosis situations such as isolated distal thrombosis of the deep and muscle veins (idDVT, iMVT), shoulder-arm vein thrombosis (SAVT), cancer-associated thrombosis (CAT) and superficial vein thrombosis (SVT). The article on hormone- and pregnancy-associated DVT, developed together with the Department of Gynecology at the University Hospital of Zurich, discusses the importance of hormonal contraception and menopausal hormone replacement therapy (HRT) as thrombogenic risk factor as well as special features in the diagnosis and treatment of thrombosis in pregnancy., Competing Interests: Die Autorinnen und Autoren haben keine Interessenkonflikte im Zusammenhang mit diesem Artikel deklariert., (© 2024 Aerzteverlag medinfo AG.)

Purpose: This study aimed to investigate the utility of the #Enzian classification in magnetic resonance imaging (MRI) for endometriosis assessment, focusing on inter-reader agreement, diagnostic accuracy, and the correlation of adenomyosis with deep endometriosis (DE)., Methods: This IRB- approved retrospective single-center study included 412 women who underwent MRI evaluation for endometriosis between February 2017 and June 2022. Two experienced radiologists independently analyzed MRI images using the #Enzian classification and assessed the type of adenomyosis, if any. The surgical #Enzian classification served as the gold standard for evaluating preoperative MRI results of 45 patients. Statistical analysis was performed to assess inter-reader agreement and diagnostic accuracy., Results: Inter-reader agreement was substantial to excellent (Cohen's kappa 0.75-0.96) for most compartments except peritoneal involvement (0.39). The preoperative MRI showed mostly substantial to excellent accuracy (0.84-0.98), sensitivity (0.62-1.00), specificity (0.87-1.00), positive (0.58-1.00) and negative predictive values (0.86-1.00) for most compartments, except for peritoneal lesions (0.36, 0.17, 1.00, 1.00, 0.26 respectively). A trend with a higher prevalence of concordant DE in women with MR features of external adenomyosis compared to those with internal adenomyosis was visible (p = 0.067)., Conclusions: The mr#Enzian showed mostly high inter-reader agreement and good diagnostic accuracy for various endometriosis compartments. MRI's role is particularly significant in the context of the current paradigm shift towards medical endometriosis treatment. The inclusion of information about the type of adenomyosis in the mr#Enzian classification could enhance diagnostic accuracy and inform treatment planning., (© 2024. The Author(s).)

Background: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches., Methods: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model., Results: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm 3 , reduced to 3 cm 3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS., Conclusions: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases., (© 2024. The Author(s).)

We investigated whether developing an autoimmune disorder (AID) following a high-grade epithelial ovarian cancer diagnosis improves overall survival. This retrospective study included data from women treated for high-grade serous, endometrioid, or transitional cell ovarian, fallopian tube, or peritoneal cancer FIGO stage III or IV at a Swiss cantonal gynecological cancer center (2008-2023). We used Kaplan-Meier estimates and the Cox proportional hazards model using time-varying covariates for the survival function estimation. In all, 9 of 128 patients developed an AID following a cancer diagnosis. The median time from cancer diagnosis to AID was 2 years (IQR 2-5). These women survived for a median of 3031 days (IQR 1765-3963) versus 972 days (IQR 568-1819) for those who did not develop an AID ( p = 0.001). The median overall survival of nine women with a pre-existing AID was 1093 days (IQR 716-1705), similar to those who never had an AID. The multivariate analyses showed older age ( p = 0.003, HR 1.04, 95% CI 1.013-1.064) was associated with a poorer prognosis, and developing an AID after a cancer diagnosis was associated with longer survival ( p = 0.033, HR 0.113, 95% CI 0.015-0.837). Clinical manifestations of autoimmune disorders following ovarian cancer diagnoses were associated with better overall survival (8 versus 2.7 years), indicating an overactive immune response may improve cancer control.

We present a new systematic, comprehensive, checklist-based sonographic assessment of endometriosis in the female true pelvis. Emphasis is placed on practical skills teaching. The newly introduced White Sliding Line (WSL) is the core structure. The WSL separates five compartments (anterior, central, posterior, and lateral right and left) containing dedicated endometriosis signs of mobility and morphology to be checked. This approach relies on the 2016 IDEA Consensus and further developments. It directly connects to the 2021 #ENZIAN Classification Standard. In practice, evaluation follows the proposed checklist in all compartments, judging first sliding mobility between organs and structures in a highly dynamic investigation. A rigorous search for deep endometriosis (DE) is then performed. We treat adhesions due to their great clinical importance and possible, reliable diagnosis by TVS as the fifth endometriosis unit, next to endometrioma, DE, adenomyosis, and superficial endometriosis. Including superficial (peritoneal) endometriosis is a future goal., Competing Interests: Julian Metzler: Founder of Scanvio Medical AG.Michael Bajka: Founder of Scanvio Medical AG., (Thieme. All rights reserved.)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer., Competing Interests: Prof. Dr. med. Marc Thill was a member of advisory board Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, and Sysmex; received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, and Servier; received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm medical, Roche, RTI Surgical, and Seagen; received congress support from Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, and Sirius Medical; has received lecture honoraria from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, and ZP Therapeutics; has received trial funding from Endomag, Exact Sciences; and received trial honoraria (institutional) from AstraZeneca, Biom’Up, Cairn Surgical, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, ExactScience, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, and Guardant Health. Prof. Dr. med. Ute-Susann Albert has received lectures from Pfizer, Novartis, AstraZeneca, was a member of advisory board Daiichi Sankyo, and Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, and ExactSciences; received study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, and ExactSciences; and received travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Dr. med. Ingo Bauerfeind has received honoraria and travel reimbursement from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF-Kongress Management. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures from Astra Zeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards from Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, and AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, and B-Rayz. Prof. Dr. med. Peter A. Fasching participate on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan; and has received consulting from Novartis, Pfizer, Roche, Daiichi Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, and Mylan. Medical Writing: Merck, to institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Tanja N. Fehm has receiverd honoraria from Onkowissen. Prof. Dr. med. Michael Friedrich was a member of advisory board: Gilead Sciences has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, and GynUpdate, Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, and Zuelligpharma; received other from Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daichi Sankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, and Daiichi; has received honoraria for consulting/advisory board from Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, and Gilead; and has received travel grants from Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. med. Christian Jackisch was a member of advisory board Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen and received lecture from Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, and StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke was a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; has received lecture from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; received other honoraria from Gilead Science and POMME; and stockholding Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe was a member of advisory board: Lilly; has received lecture from AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug has received lecture from Merck Sharp and Dohme, Pfizer, Astra Zeneca, onkowissen, med update; was a member of advisory board: Gilead; and has received research funding from Merch KGaA and Deutsche Krebshilfe. Prof. Dr.med. Thorsten Kühn was a member of advisory board/lecture Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly; and has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received lecture from Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!, and Stemline; has received other honoraria from Roche, Daiichi Sankyo, and Sonoscape; was a member of advisory board Lilly, MSD, Roche, Astra Zeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, and Exact Science. Prof. Dr. med. Sibylle Loibl was a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, and Stemline-Menarini; invited speaker, personal: Medscape; and has received trial funding/others from Astra Zeneca, Abbvie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, and VM Scope GmbH. Prof. Dr. med. Diana Lüftner D.L. has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche, and TEVA. Prof. Dr. med. Michael Patrick Lux M.P.L. has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. Prof. Dr. med. Nicolai Maass was a member of advisory board Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen has received lecture from Astra Zeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis and has received lecture from Pfizer and Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftungwas a member of advisory board MSD, Novartis, and Myriad; and has received lecture from Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. med. Kerstin Rhiem has received honoraria from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Achim Rody was a member of advisory board AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead; has received lecture from Pfizer, Celgene, Eisai; and has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt M.S. reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche; has received honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connectmedica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, streamedup, and Tesaro; and has received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, and Roche. Prof. Dr. med. Florian Schütz has received lecture from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, and Roche Pharma; was a member of advisory board Lilly, MSD, Gilead, Atheneum Partners, and ClinSol; and received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board Astra Zeneca, Exact Sciences, and Daiichi Sankyo; has received lecture from AstraZeneca and Diacentus; and has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received lecture from DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, and LÄK Hessen Akademie was a member of advisory board: MSD, Roche. Prof. Dr. med. Erich Solomeyer has received honoraria from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, Astra Zeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, and Roche and received lecture from Astra Zeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, and Roche. Prof. Dr. med. Christoph Thomssen has received compensation for advisory boards, lectures or publications from Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch M. U. has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, and Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received lecture from Astra Zeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, and Onkowissen and has received Travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel has received compensation for advisory boards, lectures, trial funding advisory board from Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, and Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant Agendia, Amgen, Apogepha, Aristo, Astra Zeneca, Celgene, Clovis Oncology, Daiichi Sankyo, Eisai, Esteve, Exact Sciences, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, and MediSeminar. Prof. Dr. med. Volkmar Müller has received speaker honoraria Astra Zeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, and i-MED Institute; has received consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Seagen, Gilead, and Stemline; has received institutional research support from Novartis, Roche, Seagen, Genentech, and Astra Zeneca; and has received travel grants from Astra Zeneca, Roche, Pfizer, Daiichi Sankyo, and Gilead. Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen and has received travel compensation from Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Jörg Heil has none to declare., (© 2024 S. Karger AG, Basel.)

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024., Results and Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon has received honoraria for lectures and/or consulting from Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, ExactSciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer, Lilly, Daiichi Sankyo, Gilead, and Pierre Fabre. Prof. Dr. med. Ute-Susann Albert has received honoraria for lectures from Pfizer, Novartis, AstraZeneca and is a member of advisory board Daiichi Sankyo, Pfizer. Prof. Dr. Malgorzata Banys-Paluchowski has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Stemline, Samsung,Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Medical, Syantra, Pierre Fabre, ExactSciences, study support from EndoMag, Mammotome, Merit Medical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, AstraZeneca, Daiichi Sankyo, and Roche. Prof. Dr. med. Jens-Uwe Blohmer has received honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen. Prof. Dr. med. Wilfried Budach has received honoraria for lectures and advisory boards: Merck, BMS, Jörg Eickeler Veranstaltungen, med publico GmbH, BVDST. Prof. Dr. med. Peter Dall has received honoraria for lectures and advisory boards from Novartis, Pierre Fabré, MSD, Lilly, AstraZeneca. Prof. Dr. Nina Ditsch was a member of advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead Sciences, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen. Prof. Dr. med. Eva Maria Fallenberg has received research grant from DFG and received speaker honorarium from GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO, B-Rayz. Prof. Dr. med. Peter A. Fasching: participation on a data safety monitoring board or advisory board: Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, has received honoraria for lecture, speakers bureaus, manuscript writing, or educational events from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan, consulting from Novartis, Pfizer, Roche, Daiichi-Sankyo, AstraZeneca, Lilly, Eisai, Merck Sharp and Dohme, Pierre Fabre, SeaGen, Agendia, Sanofi Aventis, Gilead, Mylan. Medical Writing: Merck. To institution: Biontech, Cepheid, Pfizer. Prof. Dr. med. Michael Friedrich is a member of the advisory board Gilead Sciences and has received other honoraria from Roche, MSD. Prof. Dr. med. Bernd Gerber has received travel support from Pfizer. PD Dr. med. Oleg Gluz has received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sanyko, Eisai, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia, MedConcept, GynUpdate, and minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Nadia Harbeck, MD has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Viatris, Zuelligpharma, other are Co-Director West German Study Group (WSG). Prof. Dr. med. Andreas Daniel Hartkopf has received honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. med. Jens Huober has received honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Seagen, Gilead, Daiichi and honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Daiichi, Gilead and received travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch is a member of advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke is a member of advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen, has received honoraria for lectures from NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Theraclion SA. Prof. Dr. med. Hans-Heinrich Kreipe is a member of advisory board: Lilly, has received honoraria for lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug has received honoraria for lecture from Merck Sharp and Dohme, Pfizer, AstraZeneca, Onkowissen, med update is a member of advisory board: Gilead, has received research funding from Merch KGaA, Deutsche Krebshilfe. Prof. Dr. med. Thorsten Kühn is a member of advisory board/lecture: Sysmex, Neodynamics, Pfizer, MSD, Merit Medical, Sirius Medical, Hologic, Endomag, Lilly has received trial funding from Merit Medical, Endomag, Mammotome. Prof. Dr. med. Sherko Kümmel has received honoraria for lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Pfizer, Seagen, Gilead, Agendia; Hologic, PINK!; Stemline, other honoraria from Roche, Daiichi Sankyo, Sonoscape, is a member of advisory board: Lilly, MSD, Roche, AstraZeneca, Stemline, Novartis, Daiichi Sankyo, MSD, Seagen, Gilead, Exact Science. Prof. Dr. med. Sibylle Loibl is a member of advisory board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Seagen, Stemline-Menarini, invited speaker, personal: Medscape received trial funding/others from: AstraZeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, GSK, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Stemline-Menarini, VM Scope GmbH. Prof. Dr. med. Diana Lüftner has received honoraria for advisory board activities and/or oral presentations from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, GSK, high5md, Loreal, MSD, Mundipharma, Novartis, onkowissen.de, Pfizer, Pierre Fabre, Roche and TEVA. Prof. Dr. med. Michael Patrick Lux has received honoraria from Lilly, Pfizer, Roche, MSD, Hexal, Novartis, AstraZeneca, Eisai, Exact Sciences, Agendia, Daiichi-Sankyo, Grünenthal, Gilead, Pierre Fabre, PharmaMar, Samantree, Endomag, and medac for advisory boards, lectures, and travel support. Prof. Dr. med. Nicolai Maass was a member of advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen and has received honoraria for lectures from AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke was a member of advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis, has received honoraria for lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer has received trial funding from German Cancer Aid and Else Kroener-Fresenius-Stiftung, is a member of advisory board: MSD, Novartis, Myriad lecture from: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Achim Rody was a member of advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD, Gilead, lecture Pfizer, Celgene, Eisai, has received trial funding from Eisai. Prof. Dr. med. Marcus Schmidt reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, GILEAD, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss has received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, ClinSol, Clovis Oncology, coma UroGyn, Connect Medica, Daiichi Sankyo, Gilead, GSK, if-kongress, I-MED, iOMEDICO, Lilly, MCI Deutschland, med publico, Metaplan, MSD, Mylan, NanoString Technologies, Novartis, onkowissen.de, Pfizer, Pierre Fabre, promedicis, Roche, Seagen, StreamedUp, and Tesaro, received travel support from AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Pfizer, Roche. Prof. Dr. med. Florian Schütz has received honoraria for lecture Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Lilly, MSD, Novartis, ClinSol, Pfizer, Roche Pharma, was a member of advisory board: Lilly, MSD, Gilead, Atheneum Partners, ClinSol, has received travel expenses from Lilly, Gilead. Prof. Dr. med. Hans-Peter Sinn was a member of advisory board: AstraZeneca, Exact Sciences, Daiichi Sankyo, has received honoraria for lecture from AstraZeneca, Diacentus, has received trial funding from AstraZeneca. Prof. Dr. med. Christine Solbach has received honoraria for lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, Roche, AstraZeneca, MedConcept, I-Med, GBG, BVF Akademie, LÄK Hessen Akademie, was a member of advisory board: MSD, Roche. Prof. Dr. med. Elmar Stickeler was a member of advisory boards Amgen, AstraZeneca, Gilead, Iomedico, Lilly, MSD, Novartis, Seagen, Roche; has received honoraria for lecture: AstraZeneca, BSH Düsseldorf, Gilead, Iomedico, MSD, Novartis, Onkowissen, Pfizer, PharmaMar, Roche. Prof. Dr. med. Christoph Thomssen: compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, med update, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor. Prof. Dr. med. Michael Untch has received honoraria to travel support, lectures, and consulting or advisory role from AstraZeneca, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel has received honoraria for lecture: AstraZeneca, Lilly, Seagen, Daiichi Sankyo, Gilead, Pfizer and Novartis, Onkowissen. travel support from Roche and Lilly. Prof. Dr. med. Achim Wöckel compensation for advisory boards, lectures, trial funding Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Exact Sciences, Pierre Fabre, Clovis, Organon, Daiji Sankyo, Seagen, Stemline, Gilead. PD. Dr. Rachel Würstlein served as advisor, consultant, speaker, and travel grant from Agendia, Amgen, Apogepha, Aristo, AstraZeneca, Celgene, Clovis Oncology, Daiichi-Sankyo, Eisai, Esteve, Exact Sciences, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Sidekick, Stemline, Tesaro Bio, Teva, Veracyte, Viatris, Wiley, FOMF, Aurikamed, Clinsol, Pomme Med, medconcept, MCI, MediSeminar. Prof. Dr. med. Volkmar Müller has received speaker honoraria from: AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, iMED Institute, consultancy honoraria from Roche, Pierre Fabre, PINK, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Seagen, Gilead, Stemline, institutional research support from Novartis, Roche, Seagen, Genentech, AstraZeneca, travel grants form AstraZeneca, Roche, Pfizer, Daiichi Sankyo, Gilead. Prof. Dr. med. Wolfgang Janni has received research grants and/or honoraria from AstraZeneca, Celgene, Chugai, Daiichi Sankyo, Eisai, Exact Science, GSK, Janssen, Lilly, Menarini, MSD, Novartis, Sanofi-Aventis, Roche, Pfizer, Seagen, Gilead, Inivata, Guardant Health. Prof. Dr. med. Marc Thill is a member of advisory board: Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Medical, Sysmex, has received manuscript support from Amgen, ClearCut, Clovis, Organon, pfm medical, Roche, Servier, has received travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen; Congress support: Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, Sirius Medical; Lecture honoraria: Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Stemline, Sysmex, Vifor, Viatris, ZP Therapeutics has received trial funding from Endomag, Exact Sciences, and trial honoraria from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical. Prof. Dr. med. Jörg Heil: none to disclose. Dr. I. Bauerfeind received speaker honoraria from Brustkrebs Deutschland e.V., Krankenhaus Kempten, Akademie für Psychoonkologie, IF Kongressmanagement. Prof. Dr. med. Kerstin Rhiem received honoraria for lectures from AstraZeneca, Roche, Novartis, streamed up. Prof. Dr. med. Tanja N. Fehm received honoraria for lectures from Onkowissen. Prof. Dr. med. Erich-Franz Solomayer received honoraria for lectures and/or consulting from Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre., (© 2024 S. Karger AG, Basel.)

The aim of this study was to evaluate how the COVID-19 pandemic may have impacted the number and patterns of sexual assault victims within a German metropolitan city. A retrospective single center analysis of the gynecology examination reports of all women presenting to the emergency department of a university hospital after a sexual offense between 03/2013 and 02/2021 (n = 1167). Comparison of the first year of the pandemic 03/2000-03/2021) to previous years (03/2017-02/2020) and comparison of periods of government-imposed social distancing (03/12/2020-05/23/2020 and 10/23/2020-02/28/2021) with corresponding periods of pre-pandemic years. The overall number of sexual assault cases did not change during the first year of the COVID-19 pandemic. However, during the stay-at-home orders, the number of women presenting to the emergency department decreased by 38% (n=45 vs. 72). Fewer victims filed a police report during the pandemic (49.5% vs. 73.9%, p<0.001) and the lockdown period (50% vs. 76.5%, p<0.001). Less genital injuries after sexual assault were detected during the pandemic (14.3% vs. 25.2%, p<0.02), but there was an increase of illegal substance abuse (19.5% vs. 9.3%, p<0.003). During the stay-at-home orders fewer victims reported alcohol consumption (42.4% vs. 62.5 %, p<0.023). Despite the decrease in sexual offense related police reports, the number of sexual assault cases remained consistent, and the usage of illegal drugs increased during the COVID-19 pandemic. These findings represent the importance of providing support to sexual assault victims, as well as the implementation of preventative measures, especially in times of crisis., (© 2023. The Author(s).)

Clinical evidence is interpreted based on clinical studies and personal experience which can lead to different interpretations of data. This makes the opinions issued by panels of experts such as the Advanced Breast Cancer Panel which convened in November 2023 for the seventh time (ABC7) particularly important. At the conference, current issues around advanced breast cancer were evaluated by an international team of experts. In 2023 the data on CDK4/6 inhibitors was so extensive that the answers to questions about the sequencing of therapy and the potential use of chemotherapy as an alternative therapy were relatively clear. Moreover, data on antibody drug conjugates which provides a good overview of their uses is available for all molecular subtypes. Some therapeutic settings, including patients with brain metastases or leptomeningeal disease, older patients, locally advanced breast cancer and visceral crises, continue to be particularly important and were discussed in structured sessions. The scientific context of some of the topics discussed at ABC7 is presented and assessed here., Competing Interests: Conflict of Interest/Interessenkonflikt B. A. received honoria and travel grants from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, GSK, Stemline, Lilly, MSD, Eisai, Tesaro, Daiichi Sankyo and Pfizer. M. B.-P. received honoraria for lectures and advisory role from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and study support from Mammotome, Endomag and Merit Medical. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun and onkowissen.de for clinical research management and/or medical education activities. N. D. has received honoraria from MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen,Gilead, MCI Healthcare. P. A. F. received honoraria from Novartis, Pfizer, Roche, Amgen, Celgene, onkowissen.de, Daiichi Sankyo, AstraZeneca, Merck-Sharp & Dohme, Eisai, Puma and Teva. His institution conducts research with funding from Novartis and Biontech. T. N. F. has participated on advisory boards for Amgen, Daiichi Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi Sankyo, Roche, Novartis and Pfizer. A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal and Pfizer. M. H. has no conflict of interest. N. H. received honoraria for lectures and/or consulting from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. has received research Grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. A. K. has no conflict of interest. H.-C. K. has received honoraria from Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo, Zuellgen Pharma and MSD, travel support from Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro and owns stock of Theraclion SA. D. L. received honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pierre Fabre, Pfizer, Roche, Seagen, Teva. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Grünenthal, Daiichi Sankyo and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca, and Eisai. He received travel expenses from Pfizer, AstraZeneca and Daiichi-Sankyo. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Pfizer, Seagen, Pierre Fabre, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca and travel support from Roche, Celgene and Pfizer. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. has participated on advisory boards for AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre-Fabre, Seagen and Roche and has received honoraria for lectures from Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding by Exact Sciences and Endomag Manuscript support was done by Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. all honoraria went to the institution/employer: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi Aventis, Novartis, Pierre Fabre, Seagen; Gilead. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. I. W. has participated on advisory boards for Novartis, Daiichi Sankyo, Lilly, Pfizer and received speaker honoraria from AstraZeneca, Daiichi Sankyo, MSD, Novartis, Pfizer, Roche. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Celgene. R. B. has received honoraria from Astra-Zeneca, Daiichi, Eisai, Eli-Lilly, Gilead, Gruenenthal, MSD, Novartis, Pfizer, Pierre-Fabre, Puma, Roche, Seagen, Stemline, travel support from Astra Zeneca, Daiichi, MSD, Lilly, Novartis, and grants from Daiichi and MSD. R. W. has received honoraria, travel support from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Tesaro Bio, Teva, Veracyte, Viatris. The other authors have no conflict of interest to declare for this specific work./ B. A. erhielt Honorare und und Reisekosten von AstraZeneca, Gilead, Genomic Health, Roche, Novartis, GSK, Stemline, Lilly, MSD, Eisai, Tesaro, Daiichi Sankyo und Pfizer. M. B.-P. erhielt Vortragshonorare und Beraterhonorare von Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, und Forschungsförderung von Mammotome, Endomag und Merit Medical. E. B. erhielt Honorare von Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, B. Braun und onkowissen.de für klinisches Forschungsmanagement und/oder medizinische Fortbildungsaktivitäten. N. D. erhielt Honorare von MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen, Gilead, MCI Healthcare. P. A. F. erhielt Honorare von Novartis, Pfizer, Roche, Amgen, Celgene, onkowissen.de, Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme, Eisai, Puma und Teva. Seine Institution betreibt Forschung mit Unterstützung von Novartis und BioNtech. T. N. F. hat in Beiräten mitgewirkt für Amgen, Daiichi Sankyo, Novartis, Pfizer und Roche und erhielt Vortragshonorare von Amgen, Celgene, Daiichi Sankyo, Roche, Novartis und Pfizer. A. D. H. erhielt Sprecher- und Beraterhonorare von AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal und Pfizer. M. H. hat keine Interessenkonflikte zu melden. N. H. erhielt Vortragshonorare und/oder Honorare für Beratertätigkeiten von AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. erhielt Forschungsstipendien und/oder Honorare von Sanofi Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene und Johnson & Johnson. A. K. hat keine Interessenkonflikte zu melden. H.-C. K. erhielt Honorare von Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo, Zuellgen Pharma und MSD; Reisekostenzuschüsse von Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro; und besitzt Aktien von Theraclion SA. D. L. erhielt Honorare von Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Exact Sciences, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pierre Fabre, Pfizer, Roche, Seagen, Teva. M. P. L. hat in Beiräten mitgewirkt für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Grünenthal, Daiichi Sankyo und Roche und erhielt Vortragshonorare von MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca und Eisai; Reisekostenzuschüsse von Pfizer, AstraZeneca und Daiichi-Sankyo. V. M. erhielt Sprecherhonorare von Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead; Beraterhonorare von Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead; institutionelle Forschungsförderung von Novartis, Roche, Seagen, Genentech; Reisekostenzuschüsse von Roche, Pfizer, Daiichi Sankyo. E. S. erhielt Honorare von Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Pfizer, Seagen, Pierre Fabre, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. erhielt Forschungsstipendien von Celgene, Roche, Honorare von Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme und Reisekostenzuschüsse von Celgene, Pfizer, Roche. F. S. hat in Beiräten mitgewirkt für Novartis, Lilly, Amgen and Roche und erhielt Vortragshonorare von Roche, AstraZeneca, MSD, Novartis und Pfizer. H. T. erhielt Honorare von Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca und Reisekostenzuschüsse von Roche, Celgene and Pfizer. C. T. erhielt Honorare für die Teilnahme an Beiräten und für Vorträge von Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. hat in Beiräten mitgewirkt für AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre-Fabre, Seagen und Roche; erhielt Vortragshonorare von Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor und AstraZeneca; erhielt Studienfinanzierung von Exact Sciences and Endomag; Unterstützung für das Manuskript kam von Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. Alle Honorare wurden an die Institution/den Arbeitergeber abgeführt: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi Aventis, Novartis, Pierre Fabre, Seagen, Gilead. M. W. hat in Beiräten mitgewirkt für AstraZeneca, Lilly, MSD, Novartis, Pfizer und Roche. I. W. hat in Beiräten mitgewirkt für Novartis, Daiichi Sankyo, Lilly, Pfizer und erhielt Sprecherhonorare von AstraZeneca, Daiichi Sankyo, MSD, Novartis, Pfizer, Roche. A. W. hat in Beiräten mitgewirkt für Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai und erhielt Vortragshonorare von Novartis, Pfizer, Aurikamed, Roche, Celgene. R. B. erhielt Honorare von Astra-Zeneca, Daiichi, Eisai, Eli-Lilly, Gilead, Gruenenthal, MSD, Novartis, Pfizer, Pierre-Fabre, Puma, Roche, Seagen, Stemline; Reisekostenzuschüsse von Astra Zeneca, Daiichi, MSD, Lilly, Novartis und Forschungszuschüsse von Daiichi und MSD. R. W. erhielt Honorare und Reisekostenzuschüsse von Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Tesaro Bio, Teva, Veracyte, Viatris. Die anderen Autoren und Autorinnen haben keine Interessenkonflikte zu melden., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58-0.80) for CPS, 0.55 (95% CI = 0.46-0.64) for TPS, and 0.67 (95% CI = 0.56-0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types., (© 2024 Merck Sharp & Dohme LLC, a subsidary of Merck & Co., Inc., and The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Most invasive lobular breast carcinomas (ILBCs) are luminal-type carcinomas with an HER2-negative phenotype (ERBB2 or HER2 un-amplified) and CDH1 mutations. Rare variants include ERBB2-amplified subtypes associated with an unfavorable prognosis and less response to anti-HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2-amplified ILBC and compared these characteristics with ERBB2-unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin-embedded formalin-fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast-specific markers was tested by immunohistochemistry (IHC). Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2-amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2-unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2-positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2-amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC., (© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Introduction: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is still a rare extralymphatic lymphoma. As of March 1, 2023, approximately 1,355 cases of BIA-ALCL have been reported worldwide. However, no such case has yet been described with pectoral implants in male patients. Most patients with BIA-ALCL present with nonspecific implant-associated symptoms such as late-onset seroma, swollen breasts, and deformation of implants., Case Presentation: Here, we describe BIA-ALCL in a 76-year-old male patient who presented with a late-onset seroma in order to raise awareness for BIA-ALCL also in men after esthetic chest surgery with silicone pectoral implants. The patient had undergone augmentation of the pectoralis muscle with implants for esthetic reasons 9 years before. First cytological specimens showed no malignancy. A repeated cytological assessment after 6 weeks from recurring seroma showed characteristic CD30+ T-cell clones. Surgery with complete bilateral capsulectomy and implant removal was performed. Due to the early-stage ALCL being limited only to the capsule and no evidence of systemic disease, adjuvant systemic treatment was not considered necessary., Conclusion: Any persisting late-onset seroma also in male patients with pectoral implants should raise suspicion of ALCL as differential diagnosis and should be assessed with cytological examination., Competing Interests: Prof. Dr. Eike Burandt: advisory boards for Novartis and Daiichi Sankyo, and speaker’s honoria for AstraZeneca, Eisai, and NOGGO. All remaining authors have no conflicts of interest to declare., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: In KEYNOTE-119 (ClinicalTrials.gov, NCT02555657), overall survival (primary end-point) was similar between pembrolizumab and chemotherapy in patients with previously treated metastatic triple-negative breast cancer (TNBC), although the pembrolizumab treatment effect increased with tumour PD-L1 expression. We report results of prespecified health-related quality of life (HRQoL) analyses from KEYNOTE-119., Methods: Eligible patients were randomised 1:1 to pembrolizumab 200 mg Q3W intravenously for up to 35 cycles or treatment of physician's choice per local/country guidelines. Prespecified exploratory end-points were the change from baseline in HRQoL (EORTC QLQ-C30, QLQ-BR23) and to characterise utilities (EQ-5D-3L). Time to deterioration (TTD) was the time from start of treatment to first onset of a ≥10-point worsening from baseline., Results: HRQoL analyses included 187 patients with tumour PD-L1 combined positive score (CPS) ≥10. Changes from baseline at 6 weeks (primary analysis time point) were directionally better with pembrolizumab versus chemotherapy for QLQ-C30 GHS/QoL (between-group difference in least-squares mean scores of 4.21 [95% CI, -1.38 to 9.80]), QLQ-C30 functional scales (physical, role, cognitive, social), QLQ-C30 symptom scales/items (fatigue, nausea/vomiting, dyspnoea, appetite loss), and QLQ-BR23 symptom scales/items (systemic therapy side-effects, upset by hair loss). Median TTD was directionally longer for pembrolizumab versus chemotherapy for QLQ-C30 QHS/QoL (4.3 versus 1.7 months), QLQ-C30 nausea/vomiting (7.7 versus 4.8 months), and QLQ-BR23 systemic therapy side-effects (6.1 versus 3.4 months). Minimal treatment differences were observed for other HRQoL end-points., Conclusions: HRQoL results were consistent with clinical outcomes and appeared to be driven by results for patients with tumour PD-L1 CPS ≥10., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Schmid: Consultant/Honoraria: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Puma, and Roche; grant funding to institution: Astellas, AstraZeneca, Genentech, Medivation, Novartis, Oncogenex, and Roche. Oleg Lipatov: Nothing to disclose. Seock-Ah Im: consulting/advisory role: AstraZeneca, Novartis, Roche/Genentech, Pfizer, Amgen, Hanmi, Lilly, GlaxoSmithKline, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daiichi Sankyo, Idience Co. Ltd., and Bertis; research funding to institution: AstraZeneca, Pfizer, Roche/Genentech, Daewoong Pharmaceutical, Eisai Korea, and Boryung Pharm. Anthony Goncalves: Nonfinancial support/consultant (compensated to hospital): AstraZeneca, Novartis, Astellas, Pfizer, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Lilly, Mylan, Parexel, and Roche. Eva Muñoz-Couselo: Nothing to disclose. Keun Seok Lee: Consultant: Lilly, Novartis, Pfizer, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Bixink, Everest Medicine, Daiichi Sankyo, and Roche; drug supplies: Dong-A Pharm. Kenji Tamura: Nothing to disclose. Laura Testa: Funding for the current trial conduct, provision of study materials, medical writing, and article processing charges: Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; research grant: Novartis; payment or honoraria for medical education: Lilly, Novartis, Pfizer, AstraZeneca, Daiichi-Sankyo, and Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; support for attending meetings and/or travel: Roche, Gilead, and AstraZeneca; Data Safety Monitoring/Advisory board: AstraZeneca, Lilly, Novartis, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Daichi-Sankyo, and Pfizer; steering committee for trials: AstraZeneca and Lilly. Isabell Witzel: Research funding to institution: Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; personal fees: Daiichi Sankyo, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, and Roche. Shoichiro Ohtani: Lecture fees: AstraZeneca, Chugai, Lilly, and Pfizer. Nicholas Turner: Advisory board honoraria: AstraZeneca, Lilly, Pfizer, Roche/Genentech, Novartis, GlaxoSmithKline, Repare Therapeutics, Relay Therapeutics, Zentalis, Gilead, Inivata, Guardant, and Exact Sciences; research funding: AstraZeneca, Pfizer, Roche/Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Guardant Health, Invitae, Inivata, Personalis, and Natera. Stefania Zambelli: Nothing to disclose. Nadia Harbeck: Consulting/Lecture fees: AstraZeneca, Daiichi Sankyo, Lilly, Merck Sharp, and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, and Seattle Genetics. Fabrice Andre: Research grants to institution: AstraZeneca, Daiichi Sankyo, Lilly, Novartis, Pfizer, and Roche; Advisory board or speaker (compensation to institution): AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, and Guardant Health; and personal fees (advisory board): Lilly. Rebecca Dent: Advisory board: AstraZeneca, Eisai, Eli Lilly and Company, Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, and Pfizer; Consultant: Genentech; Travel: Genentech, Merck Sharp and Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and Pfizer. Jaime A. Mejia: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Xuan Zhou: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Amin Haiderali: employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Allison Martin Nguyen: Employee of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; owns stock in Merck & Co., Inc., Rahway, NJ, USA. Javier Cortes: Consulting fees: AstraZeneca, Athenex, Bioasis, BioInvent, Boehringer Ingelheim, Celgene, Cellestia, Clovis Oncology, Daiichi Sankyo, Ellipses, Erytech, Gemoab, Gilead, GSK, Hibercell, Leuko, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Polyphor, Roche, and Seattle Genetics; fees for non-CME services received directly from commercial interest or their agents (e.g., speakers' bureaus): Celgene, Daiichi Sankyo, Eisai, Lilly, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Novartis, Pfizer, Roche, and Samsung Bioepis; contracted research: Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, Pfizer, Piqur Therapeutics, Puma, Queen Mary University of London, and Roche; Ownership interest (stock, stock options, or other ownership interest excluding diversified mutual funds): MedSIR; Travel/Accommodation: Daiichi Sankyo, Eisai, Novartis, Pfizer, and Roche; Patent: HER2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Eric P. Winer: Advisory board member: LEAP; Consultant: G1 Therapeutics, Garrick Therapeutics, Genomic Health, GlaxoSmithKline, Jounce, Lilly, Novartis, Roche Genentech, Seattle Genetics, and Syros., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Around 5 percent of all patients with metastatic breast cancer go on to develop distant metastases in the meninges, also known as meningeal carcinomatosis. The median survival of these patients is between 3.5 and 4.5 months. Current treatment approaches are based on radiotherapy, systemic and intrathecal therapy. Methotrexate, liposomal cytarabine and trastuzumab are the most common substances used for intrathecal therapy. The aim of this review was to provide an overview of these intrathecal therapy options for meningeal carcinomatosis. A systematic search of the literature was carried out in PubMed using the following search terms: "meningeal metastases", "meningeal carcinomatosis", "leptomeningeal metastasis", "leptomeningeal carcinomatosis", "leptomeningeal disease", "breast cancer", "MTX", "methotrexate", "DepoCyte", "liposomal cytarabine", "trastuzumab" and "anti-HER2". This search resulted in 75 potentially relevant studies, 11 of which were included in this review after meeting the previously determined inclusion and exclusion criteria. The studies differ considerably with regards to study design, cohort size, and dosages of administered drugs. In principle, intrathecal therapy has a tolerable side-effects profile and offers promising results in terms of the median overall survival following treatment with trastuzumab for HER2-positive primary tumors. The focus when treating meningeal carcinomatosis must be on providing a multimodal individual therapeutic approach. However, comprehensive studies which compare the efficacy and side effects of individual pharmaceuticals are lacking. Because of the poor prognosis associated with meningeal carcinomatosis, an approach which treats only the symptoms (best supportive care) should always be considered and discussed with affected patients., Competing Interests: Conflict of Interest MM: no conflict of interest relating to the topic of this review. EL: no conflict of interest relating to the topic of this review. KR: no conflict of interest relating to the topic of this review. IW: no conflict of interest relating to the topic of this review. VM: speaker’s fees: AstraZeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre, Medscape. Consultancy services: Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Stemline, ClinSol. Research support to employer: Novartis, Roche, Seagen, Genentech, AstraZeneca. Travel expenses: Roche, Pfizer, Daiichi-Sankyo., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background and Purpose: To analyze clinical trial activities and patient recruitment numbers into prospective clinical studies for solid malignancies during the COVID-19 pandemic in a tertiary cancer center., Materials and Methods: Patient recruitment numbers in prospective clinical studies of solid malignancies were retrospectively analyzed for the years 2019 - 2021 at the Comprehensive Cancer Center Zurich (CCCZ). Changes in recruitment numbers were tested for association with organ-specific subunits, as well as organizational and treatment-related trial characteristics. To assess differences between categorical variables, Chi-squared test was used. For uni- and multivariate analysis, Cox proportional hazards were calculated., Results: In 2019, there were a total of 107 studies (registry trials, clinical phase I-III trials, and translational studies) recruiting 304 patients at the CCCZ. During the COVID-19 pandemic in 2020 and 2021, there were 120 and 125 active trials with a total recruitment of 355 and 666 patients, respectively. No significant differences between the subunits and study characteristics in changes of patient recruitment in clinical phase I-III trials were identified when the year prior to the COVID-19 pandemic (2019) was compared to the first year of the pandemic (2020) and to 2020-2021., Conclusions: Despite healthcare systems around the world have experienced significant disruption due to the COVID-19 pandemic, data from our tertiary cancer center showed that clinical trial activities were maintained at a high level during the pandemic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CB reported consulting or advisory roles for AstraZeneca, Pfizer, Roche, Takeda, Janssen-Cilag, Boehringer Ingelheim, Merck KGaA, and Sanofi; research funding from Bayer; and travel accommodations and expenses from AstraZeneca, Takeda and Roche; all over the last five years. MW has received research grants from Quercis and Versameb, and honoraria for lectures or advisory board participation or consulting from Bayer, Curevac, Medac, Novartis, Novocure, Orbus, Philogen, Roche and Sandoz. IO reported the following disclosures: Roche (Institutional Grant and Speakers Bureau), AstraZeneca (Advisory Board and Speakers Bureau), MSD (Advisory Board), BMS (Advisory Board), Medtronic (Institutional Grant), Intuitive (Proctorship). PR has received honoraria for lectures or advisory board participation from Alexion, Bristol-Myers Squibb, Boehringer Ingelheim, Debiopharm, Midatech Pharma, Novocure, QED, and Roche and research support from Merck Sharp and Dohme and Novocure. JM has intermittent project focused consultant or advisory relationships with Merck/Pfizer, Merck Sharp & Dohme, Amgen, Novartis, Roche, Bristol Myers Squibb and Pierre Fabre and has received travel support from Ultrasun, L’ Oreal, Merck Sharp & Dohme, Bristol Myers and Squibb und Pierre Fabre outside of the submitted work. ER received research funding by Amgen; consulting or advisory roles for Sanofi/Regeneron and Amgen; honoraria from Pierre Fabre, Lilly, Galderma, MSD, Sanofi, and BMS GmbH & Co KG; Travel expenses from Amgen and Sanofi. All other authors reported no potential conflicts of interest, (Copyright © 2023. Published by Elsevier Inc.)

The St. Gallen (SG) International Breast Cancer Conference is held every two years, previously in St. Gallen and now in Vienna. This year (2023) marks the eighteenth edition of this conference, which focuses on the treatment of patients with early-stage breast carcinoma. A panel discussion will be held at the end of this four-day event, during which a panel of experts will give their opinions on current controversial issues relating to the treatment of early-stage breast cancer patients. To this end, questions are generally formulated in such a way that clinically realistic cases are presented - often including poignant hypothetical modifications. This review reports on the outcome of these discussions and summarises the data associated with individual questions raised., Competing Interests: Conflict of Interest/Interessenkonflikt B. A. received honoria and travel grants from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo and Pfizer. M. B.-P. received honoraria for lectures and advisory role from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi-Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and study support from Mammotome, Endomag and Merit Medical. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun and onkowissen.de for clinical research management and/or medical education activities. N. D. has received honoraria from MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen,Gilead, MCI Healthcare. P. A. F. reports personal fees from Novartis, grants from Biontech, personal fees from Pfizer, personal fees from Daiichi-Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from Merck Sharp & Dohme, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. T. N. F. has participated on advisory boards for Amgen, Daiichi-Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi-Sankyo, Roche, Novartis and Pfizer. A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo, Hexal and Pfizer. N. H. received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi-Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. has received research Grants and/or honoraria from Sanofi-Aventis, Daiichi-Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. H.-C. K. has received honoraria from Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi-Sankyo and MSD, travel support from Carl, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi-Sankyo, Tesaro and owns stock of Theraclion SA and Phaon Scientific GmbH. D. L. received honoraria from Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi-Sankyo, PharmaMar and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, Gilead, AstraZeneca, and Eisai. He is editorial board member of medactuell from medac. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi-Sankyo. E. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Pfizer, Seagen, Pierre Fabre, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca and travel support from Roche, Celgene and Pfizer. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. has participated on advisory boards for AstraZeneca, Clovis, Daiichi-Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen and Roche and has received honoraria for lectures from Amgen, Clovis, Daiichi-Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding by Exact Sciences and Endomag. Manuscript support was done by Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. : All honoraria went to the institution/employer: Abbvie, Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi-Aventis, Novartis, Pierre Fabre, Seagen, Gilead. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. I. W. has participated on advisory boards for Novartis, Daichii-Sankyo, Lilly, Pfizer and received speaker honoraria from AstraZeneca, Daichii-Sankyo, MSD, Novartis, Pfizer, Roche. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Celgene. R. W. has received honoraria, travel support from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Tesaro Bio, Teva, Veracyte, Viatris. The other authors have no conflict of interest to declare for this specific work. B. A. erhielt Vergütungen und Reisezuschüsse von AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo und Pfizer. M. B.-P. erhielt Vergütungen für Vorträge und eine beratende Rolle von Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi-Sankyo, Gilead, Sirius Pintuition, Pierre Fabre und eine Studienförderung von Mammotome, Endomag und Merit Medical. E. B. erhielt Vergütungen von Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun und onkowissen.de für klinisches Forschungsmanagement und/oder medizinische Bildungsaktivitäten. N. D. erhielt Vergütungen von MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen, Gilead, MCI Healthcare. P. A. F. meldet private Vergütungen von Novartis, Zuschüsse von Biontech, private Vergütungen von Pfizer, private Vergütungen von Daiichi-Sankyo, private Vergütungen von AstraZeneca, private Vergütungen von Eisai, private Vergütungen von Merck Sharp & Dohme, Zuschüsse von Cepheid, private Vergütungen von Lilly, private Vergütungen von Pierre Fabre, private Vergütungen von SeaGen, private Vergütungen von Roche, private Vergütungen von Hexal, private Vergütungen von Agendia, private Vergütungen von Gilead. T. N. F. war Mitglied von Beratungsgremien für Amgen, Daiichi-Sankyo, Novartis, Pfizer und Roche und erhielt Vergütungen für Vorträge von Amgen, Celgene, Daiichi-Sankyo, Roche, Novartis und Pfizer. A. D. H. erhielt Vergütungen als Redner und Berater von AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi-Sankyo, Hexal und Pfizer. N. H. erhielt Vergütungen für Vorträge und/oder Beratungen von Amgen, AstraZeneca, Daiichi-Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. erhielt Forschungszuschüsse und/oder Vergütungen von Sanofi-Aventis, Daiichi-Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene und Johnson & Johnson. H.-C. K. erhielt Vergütungen von Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi-Sankyo und MSD, Reisebeihilfen von Carl, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi-Sankyo, Tesaro und besitzt Aktien von Theraclion SA und Phaon Scientific GmbH. D. L. erhielt Vergütungen von Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi-Sankyo, PharmaMar und Roche und erhielt Vergütungen für Vorträge von MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, Gilead, AstraZeneca und Eisai. Er ist Mitglied des Redaktionsausschusses von medactuell von medac. V. M. erhielt Vergütungen als Redner von Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Vergütungen als Berater von Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutionelle Forschungsförderung von Novartis, Roche, Seagen, Genentech. Reisezuschüsse: Roche, Pfizer, Daiichi-Sankyo. E. S. erhielt Vergütungen von Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Pfizer, Seagen, Pierre Fabre, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. erhielt Forschungszuschüsse von Celgene, Roche, Vergütungen von Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme und Reisebeihilfe von Celgene, Pfizer, Roche. F. S. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen and Roche und erhielt Vergütungen für Vorträge von Roche, AstraZeneca, MSD, Novartis und Pfizer. H. T. erhielt Vergütungen von Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca und Reisebeihilfe von Roche, Celgene und Pfizer. C. T. erhielt Vergütungen für Beratungsgremien und Vorträge von Amgen, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. war Mitglied von Beratungsgremien für AstraZeneca, Clovis, Daiichi-Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen und Roche und erhielt Vergütungen für Vorträge von Amgen, Clovis, Daiichi-Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor und AstraZeneca und erhielt Studienfinanzierungen von Exact Sciences und Endomag. Manuskript-Beihilfe wurde erhalten von Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. : Alle Vergütungen gingen an die Einrichtung/den Arbeitgeber: Abbvie, Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi-Aventis, Novartis, Pierre Fabre, Seagen, Gilead. M. W. war Mitglied von Beratungsgremien für AstraZeneca, Lilly, MSD, Novartis, Pfizer und Roche. I. W. war Mitglied von Beratungsgremien für Novartis, Daiichi-Sankyo, Lilly, Pfizer und erhielt Vergütungen als Redner von AstraZeneca, Daiichi-Sankyo, MSD, Novartis, Pfizer, Roche. A. W. war Mitglied von Beratungsgremien für Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai und erhielt Vergütungen für Vorträge von Novartis, Pfizer, Aurikamed, Roche, Celgene. R. W. erhielt Vergütungen, Reisebeihilfe von Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Tesaro Bio, Teva, Veracyte, Viatris. Die anderen Autoren melden für diese besondere Arbeit keinen Interessenkonflikt an., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2023 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC)., Competing Interests: The authors have the following conflicts of interest: Prof. Dr. Med. Marc Thill: MT received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, NeoDynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, and Sysmex; for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, and Servier; for travel expenses from Amgen, Art Tempi, AstraZeneca, ClearCut, Clovis, ConnectMedica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, NeoDynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, and Seagen; for congress support Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Hexal, NeoDynamics, Novartis, Pfizer, Roche, and Sirius Medical; for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, ConnectMedica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther, Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, STREAMED UP, Sysmex, Vifor, and Viatris; for trial funding from Endomag, Exact Sciences; and institutional fees from AstraZeneca, Biom’Up, Celgene, ClearCut, NeoDynamics, Novartis, pfm medical, Roche, and RTI Surgical. Prof. Dr. Med. Ute-Susann Albert, lectures: Pfizer, Novartis, and AstraZeneca; advisory board: Daiichi Sankyo. PD Dr. Malgorzata Banys-Paluchowski: M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and Exact Sciences; study support from Endomag, Mammotome, Merit Medical, Gilead, Hologic, and Exact Sciences; and travel/congress support from Eli Lilly, Exact Sciences, Pierre Fabre, Pfizer, Daiichi Sankyo, and Roche. Dr. Med. Ingo Bauerfeind, honoraria for lectures: Pfizer, Roche, and Seagen. Prof. Dr. Med. Jens-Uwe Blohmer, honoraria for advisory boards and lectures: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, and Seagen. Prof. Dr. Med. Wilfried Budach, lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, and BVDST. Prof. Dr. Med. Peter Dall, honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, and Roche. Prof. Dr. Nina Ditsch, advisory boards and speakers bureaus advisory boards and speakers bureaus: AstraZeneca, Aurikamed, BGGF, Daiichi Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molecular Health, MSD, Novartis, Onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, and Seagen. Prof. Dr. Med. Eva Maria Fallenberg, research grant: DFG; speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. Med. Peter A. Fasching, advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi-Aventis, and Gilead Science; lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, and Gilead Sciences; and other: Onkowissen, art tempi. Prof. Dr. Med. Tanja N. Fehm, Onkowissen. Prof. Dr. Med. Michael Friedrich, advisory board: Gilead Sciences; other honoraria: Roche and MSD. Prof. Dr. Med. Bernd Gerber, lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, and MedConcept; and others: Pfizer. PD Dr. Med. Oleg Gluz, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, and Agendia; and minority share holder: Westdeutsche Studiengruppe (WSG)mmc1. Prof. Dr. Med. Nadia Harbeck, honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, and Zuellig Pharma; minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. Med. Andreas Hartkopf, honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, Daiichi Sankyo, Eisai, Exact Science, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre Fabre, Seagen, Stemline, and Verazyte. Prof. Dr. Med. Jörg Heil, none. Prof. Dr. Med. Jens Huober, trial funding: Novartis and Lilly; honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; AbbVie, Seagen, Gilead, and Daiichi; honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, AbbVie, Daiichi, and Gilead; and travel grants: Roche, Pfizer, Daiichi, and Gilead. Prof. Dr. Med. Christian Jackisch, advisory board: AstraZeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre Fabre, Roche, and Seagen; lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre Fabre, Exact Sciences, MSD, Gyn Update, and STREAMED UP. Prof. Dr. Med. Cornelia Kolberg-Liedtke, advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, and Onkowissen; and lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, and Daiichi Sankyo; other: Gilead Science and POMME; stockholding: Phaon Scientific and Theraclion SA; and trial Funding: Gilead Science. Prof. Dr. Med. Hans-Heinrich Kreipe, advisory board: Lilly; lecture: AstraZeneca, Roche, Daiichi Sankyo, and Pfizer. PD Dr. David Krug, lecture: Merck Sharp and Dohme, Onkowissen, and Pfizer; research funding: Merck KGaA; and advisory board: Gilead. Prof. Dr. med. Thorsten Kühn, advisory board: Sysmex and NeoDynamics; trial funding: Merit Medical, Endomag, and Mammotome; and lecture: Pfizer. Prof. Dr. Med. Sherko Kümmel, lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, and Agendia; other honoraria: Roche, Daiichi Sankyo, and Sonoscape; and advisory board: Lilly, MSD, and Roche. Prof. Dr. Med. Sibylle Loibl, board, advisory board, institutional: AbbVie, Amgen, AstraZeneca, BMS, Celgene, DSI, EirGenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeutics, Puma, Roche, Samsung, Sanofi, and Seagen; invited speaker, institutional: AstraZeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, and Seagen; invited speaker, personal: Medscape and Stemline-Menarini; trial funding/others: AstraZeneca, AbbVie, Celgene, Daiichi Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope Gmbp. Prof. Dr. Med. Diana Lüftner, lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, and high4md; advisory board: Lilly, Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, and AstraZeneca; and other: Novartis. Prof. Dr. Med. Michael Patrick Lux: M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar, Roche, SamanTree, Sysmex, and Hexal; and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. Med. Nicolai Maass, advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, and Seagen; and lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, and Roche. Prof. Dr. Med. Christoph Mundhenke, advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, and Novartis; and lecture: Pfizer and Novartis. Prof. Dr. Med. Toralf Reimer; trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung; advisory board: MSD, Novartis, and Myriad; and lecture: Pfizer, Novartis, Roche, and AstraZeneca. Prof. Dr. Med. Kerstin Rhiem, lecture: AstraZeneca, Amgen, and Roche. Prof. Dr. Med. Achim Rody, advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, and MSD; lecture: Pfizer, Celgene, and Eisai; and trial funding: Eisai. Prof. Dr. Med. Marcus Schmidt: MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen; his institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. Med. Andreas Schneeweiss, lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, NanoString, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, and STREAMED UP; and other: Thieme. Prof. Dr. Med. Florian Schütz, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, and Roche Pharma; and advisory board: Lilly, MSD, and Atheneum Partners; and travel expenses: Lilly, Daiichi Sankyo, and Amgen. Prof. Dr. Med. Hans-Peter Sinn, advisory board: Exact Sciences and Daiichi Sankyo; lecture: AstraZeneca; and trial Funding: AstraZeneca. Prof. Dr. Med. Christine Solbach, lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy; advisory board: MSD and Roche. Prof. Dr. Med. Erich-Franz Solomayer, Roche, Amgen, Celgen, Tesaro, AstraZeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson & Johnson, Daiichi Sankyo, Gilead, Exact Sciences, GSK, and Pierre Fabre. Prof. Dr. Med. Elmar Stickeler, advisory boards: Gilead, Iomedico, Lilly, MSD, and Seagen; and lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, and Roche. Prof. Dr. Med. Christoph Thomssen, compensation for advisory boards, lectures or publications: Amgen, AstraZeneca, Aurikamed, Daiichi Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, NanoString, Novartis, Onkowissen, Pfizer, Roche, Seagen, and Vifor. Prof. Dr. Med. Michael Untch: M. U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiichi Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai; all honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel, lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, and Gilead; other: Onkowissen. Prof. Dr. Med. Achim Wöckel; advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, and Organon. PD. Dr. Rachel Würstlein, Agendia, Amgen, Aristo, AstraZeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, NanoString, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme-med, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, and Viatris. Prof. Dr. Med. Volkmar Müller: VM received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, Clinsol, Daiichi Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics, and Nektar; institutional research support from Novartis, Roche, Seattle Genetics, and Genentech; and travel grants: Roche, Pfizer, and Daiichi Sankyo. Prof. Dr. Med. Wolfgang Janni, lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, and Gilead Science; trial Funding: Amgen, AstraZeneca, Lilly, Novartis, and Roche. Prof. Dr. Tjoung-Won Park-Simon, honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, and Seagen; and travel compensation: Roche, AstraZeneca, and Pfizer., (© 2023 S. Karger AG, Basel.)

Background: Each year the interdisciplinary Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), German Gynecological Oncology Group Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer., Summary: The updated evidence-based treatment recommendation for early and metastatic breast cancer has been released in March 2023., Key Messages: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter., Competing Interests: Prof. Dr. Tjoung-Won Park-Simon. Honoraria for lectures and/or consulting: Roche, AstraZeneca, GSK, Pfizer, Lilly, MSD, Exact Sciences, Daiichi Sankyo, Seagen, Novartis, Gilead Science, NCO, Onkowissen, Exact Sciences, Seagen. Travel compensation: Roche, AstraZeneca, Pfizer. Prof. Dr. med. Ute-Susann Albert. Lectures: Pfizer, Novartis, AstraZeneca. Advisory board: Daiichi Sankyo. PD. Dr. Malgorzata Banys-Paluchowski. M.B. has received honoraria for lectures and advisory from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, AstraZeneca, Eisai, Amgen, Samsung, Canon, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre and ExactSciences, study support from EndoMag, Mammotome, MeritMedical, Gilead, Hologic, ExactSciences, and travel/congress support from Eli Lilly, ExactSciences, Pierre Fabre, Pfizer, Daiichi Sankyo and Roche. Dr. med. Ingo Bauerfeind. Honoraria for lectures: Pfizer, Roche, Seagen. Prof. Dr. med. Jens-Uwe Blohmer. Honoraria for advisory boards and lectures: Astrazeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Seagen Prof. Dr. med. Wilfried Budach. Lecture: Merck, BMS, Jörg Eickeler Veranstaltungen, medpublico GmbH, BVDST. Prof. Dr. med. Peter Dall, Honoraria for lectures and advisory boards: Novartis, Pierre Fabre, Gilead, MSD, Daiichi Sankyo, Lilly, AstraZeneca, Pfizer, Roche. Prof. Dr. Nina Ditsch. Advisory Boards and speakers bureaus. AstraZeneca, Aurikamed, BGGF, Daiichi-Sankyo, Elsevier Verlag, ESO, Exact Sciences, Gilead, GSK, if-Kongress, KelCon, Leopoldina Schweinfurt, Lilly, Lukon, Molekular Health, MSD, Novartis, onkowissen, Pfizer, RG-Ärztefortbildungen, Roche, Seagen Prof. Dr. med. Eva Maria Fallenberg. Research grant: DFG. Speaker honorarium: GE Healthcare, Bayer Healthcare, Guerbet, Siemens, BD, Roche, EUSOBI, ESOR, ESMO. Prof. Dr. med. Peter A. Fasching. Advisory board: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Agendia, Pierre Fabre, Sanofi Aventis, Gilead Science. Lecture: Pfizer, Novartis, Roche, Daiichi Sankyo, Eisai, AstraZeneca, Lilly, MSD, Seagen, Gilead Sciences. Other: Onkowissen, art tempi. Prof. Dr. med. Tanja N. Fehm. Onkowissen Prof. Dr. med. Michael Friedrich. Advisory Board: Gilead Sciences. Other honoraria: Roche, MSD. Prof. Dr. med. Bernd Gerber. Lecture honoraria: Roche, AstraZeneca, Seagen, Novartis, Pfizer, MedConcept. Others: Pfizer. PD Dr. med. Oleg Gluz. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead Science, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Exact Sciences, Agendia. Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Nadia Harbeck. Honoraria for lectures and/or consulting: Amgen, AstraZeneca, Daiichi Sanyko, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Sanofi, Seagen, Viatris, Zuelligpharma Minority share holder: Westdeutsche Studiengruppe (WSG). Prof. Dr. med. Andreas Hartkopf. Honoraria for consulting and speaking engagements from AstraZeneca, Agendia, Amgen, Clovis, DaichiiSankyo, Eisai, ExactScience, Gilead, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Pfizer, Roche, Pierre-Fabre, Seagen, Stemline and Verazyte. Prof. Dr. med. Jörg Heil. None. Prof. Dr. med. Jens Huober. Trial funding: Novartis, Lilly. Honoraria for lectures: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Celgene; Abbvie, Seagen, Gilead, Daiichi. Honoraria for consulting/advisory board: Lilly, Novartis, Roche, Pfizer, AstraZeneca, MSD, Abbvie, Daiichi, Gilead. Travel grants: Roche, Pfizer, Daiichi, Gilead. Prof. Dr. med. Christian Jackisch. Advisory board: Astra Zeneca, Novartis, Lilly, Gilead, Exact Sciences, Pfizer, Roche, GSK, Pierre-Fabre, Roche, Seagen; Lecture: Art tempi, AstraZeneca, Lilly, Novartis, Roche, Amgen, Pierre-Fabre, Exact Sciences, MSD, GynUpdate, StreamedUp. Prof. Dr. med. Cornelia Kolberg-Liedtke. Advisory board: SeaGen, Exact Sciences, Pfizer, Novartis, AstraZeneca, Lilly, SeaGen, Daiichi Sankyo, Agendia, Gilead, Onkowissen; Lecture: Novartis Ireland, NOGGO, CECOG, PINK, Pfizer, Roche, AstraZeneca, Carl Zeiss Meditec, Lilly, SeaGen, Daiichi Sankyo. Other: Gilead Science, POMME. Stockholding: Phaon Scientific, Theraclion SA. Trial Funding: Gilead Science. Prof. Dr. med. Hans-Heinrich Kreipe. Advisory board: Lilly. Lecture: AstraZeneca, Roche, Daiichi Sankyo, Pfizer. PD Dr. David Krug. Lecture: Merck Sharp & Dohme, onkowissen, Pfizer. Research funding: Merck KGaA. Advisory Board: Gilead. Prof. Dr.med. Thorsten Kühn. Advisory Board: Sysmex, Neodynamics. Trial funding: Merit Medical, Endomag, Mammotome. Lecture: Pfizer. Prof. Dr. med. Sherko Kümmel. Lecture: Roche, Lilly, Exact Sciences, Novartis, Amgen, Daiichi Sankyo, AstraZeneca, Somatex, MSD, Pfizer, pfm medical, Seagen, Gilead Science, Agendia. Other honoraria: Roche, Daiichi Sankyo, Sonoscape Advisory board: Lilly, MSD, Roche. Prof. Dr. med. Sibylle Loibl. Advisory Board, institutional: Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, GSK, Gilead Science, Lilly, Merck, Novartis, Olema, Pfizer, Pierre Fabre, Relay Therapeuticas, Puma, Roche, Samsung, Sanofi, Seagen Invited speaker, institutional: Astra Zeneca, DSI, Gilead, Novartis, Pfizer, Pierre Fabre, Roche, Seagen Invited speaker, personal: Medscape, Stemline-Menarini. Trial funding/others: Astra Zeneca, Abbvie, Celgene, Daiichi-Sankyo, Greenwich Life Sciences, Immunomedics/Gilead, Molecular Health, Novartis, Pfizer, Roche, Seagen, VM Scope GmbH. Prof. Dr. med. Diana Lüftner. Lecture: Lilly, Roche, MSD, Onkowissen, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Loreal, high4md. Advisory board: Lilly, Roche, MSD, Novartis, Pfizer, Daiichi Sankyo, Gilead, AstraZeneca, Other: Novartis. Prof. Dr. med. Michael Patrick Lux. M.P.L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi-Sankyo, PharmaMar, Roche, SamanTree, Sysmex and Hexal and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi-Sankyo, Grünenthal, pfm, Gilead, AstraZeneca, and Eisai. Prof. Dr. med. Nicolai Maass. Advisory board: Amgen, AstraZeneca, Clovis, Daiichi Sankyo, GSK, Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen Lecture: AstraZeneca, Daiichi Sankyo, GSK, Lilly, Novartis, Pfizer, Roche. Prof. Dr. med. Christoph Mundhenke. Advisory board: AstraZeneca, Pfizer, Daiichi Sankyo, Seagen, Novartis. Lecture: Pfizer, Novartis. Prof. Dr. med. Toralf Reimer. Trial funding: German Cancer Aid and Else Kroener-Fresenius-Stiftung. Advisory board: MSD, Novartis, Myriad. Lecture: Pfizer, Novartis, Roche, AstraZeneca. Prof. Dr. med. Kerstin Rhiem. Lecture: AstraZeneca, Amgen, Roche. Prof. Dr. med. Achim Rody. Advisory board: AstraZeneca, Novartis, Roche, Exact Sciences, Pierre Fabre, Lilly, Seagen, Amgen, MSD. Lecture: Pfizer, Celgene, Eisai. Trial funding: Eisai. Prof. Dr. med. Marcus Schmidt. MS reports personal fees from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, and SeaGen, His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre, and SeaGen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. Prof. Dr. med. Andreas Schneeweiss. Lecture: Amgen, AstraZeneca, Aurikamed, Clinsol, ConnectMedica, Gilead Science, GSK, I-Med, Lilly, MSD, Nanostring, Novartis, Onkowissen, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, StreamedUp. Other: Thieme. Prof. Dr. med. Florian Schütz. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, ExactSciences, Gilead, Pfizer, MSD, Novartis, Onkowissen, Roche Pharma. Advisory board: Lilly, MSD, Atheneum Partners. Travel expanses: Lilly, Daiichi-Sankyo, Amgen, Prof. Dr. med. Hans-Peter Sinn. Advisory board: Exact Sciences, Daiichi Sankyo. Lecture: AstraZeneca. Trial Funding: AstraZeneca. Prof. Dr. med. Christine Solbach. Lecture: DiaLog Service GmbH, Jörg Eickeler, Pfizer, MedConcept, Medicultus, GBG, Dt. Röntgengesellschaft, BVF Akademie, LÄK Hessen Akademie, Meet the Expert Academy. Advisory board: MSD, Roche. Prof. Dr. med. Erich-Franz Solomayer. Roche, Amgen, Celgen, Tesaro, Astra Zeneca, Pfizer, Storz, Erbe, Gedeon Richter, Eisai, Medac, MSD, Vifor, Teva, Ethikon, Johnson Johnson, Daiichi-Sankyo, Gilead, Exact Sciences, GSK, Pierre Fabre. Prof. Dr. med. Elmar Stickeler. Advisory boards: Gilead, Iomedico, Lilly, MSD, Seagen Lecture: Pfizer, Bsh Düsseldorf, Gilead, Iomedico, PharmaMar, Onkowissen, Roche. Prof. Dr. med. Christoph Thomssen. Compensation for advisory boards, lectures or publications. Amgen, AstraZeneca, Aurikamed, Daiichi-Sankyo, Forum Sanitas, Gilead, Jörg Eickeler, Hexal, Lilly, Medupdate, MSD, Nanostring, Novartis, Onkowissen, Pfizer, Roche, Seagen, Vifor Prof. Dr. med. Michael Untch. M.U. has received honoraria for lectures and consulting or advisory role from AstraZeneca, Art tempi, Amgen, Daiji Sankyo, Lilly, Roche, Pfizer, MSD Oncology, Pierre Fabre, Sanofi-Aventis, Myriad, Seagen, Novartis, Gilead, Stemline, Genzyme, Agendia, Onkowissen, Eisai, All honoraria and fees to the employer/institution. Prof. Dr. Isabell Witzel. Lecture: Daiichi Sankyo, Pfizer, Roche, MSD, Lilly, Seagen, AstraZeneca, Gilead. Other: Onkowissen Prof. Dr. med. Achim Wöckel. Advisory board: Amgen, AstraZeneca, Aurikamed, Celgene, Eisai, Lilly, Novartis, Pfizer, Roche, Tesaro, Sirtex, MSD, Genomic Health, Pierre Fabre, Clovis, Organon. PD. Dr. Rachel Würstlein. Agendia, Amgen, Aristo, Astra Zeneca, Aurikamed, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, FOMF, Gilead, Glaxo Smith Kline, Hexal, Lilly, MCI, medconcept, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, Pomme Med, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics/Seagen, Stemline, Tesaro Bio, Teva, Veracyte, Viatris Prof. Dr. med. Volkmar Müller. V.M. received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Roche, Pierre Fabre, ClinSol, Daiichi-Sankyo, Eisai, Lilly, Tesaro, Seattle Genetics and Nektar. Institutional research support from Novartis, Roche, Seattle Genetics, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. Prof. Dr. med. Wolfgang Janni. Lecture: Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Gilead Science. Trial Funding: Amgen, AstraZeneca, Lilly, Novartis, Roche. Prof. Dr. med. Marc Thill. M.T. received personal fees for consulting from Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Norgine, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, pfm Medical, Pierre-Fabre, Roche, RTI Surgical, Seagen, Sirius Pintuition, Sysmex, for manuscript support from Amgen, ClearCut, Clovis, pfm medical, Roche, Servier, for travel expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, Seagen, for congress support Amgen, AstraZeneca, Celgene, Daiichi Sanyko, Hexal, Neodynamics, Novartis, Pfizer, Roche, Sirius Medical, for lectures from Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al. Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer, pfm medical, Roche, Seagen, StreamedUp, Sysmex, Vifor, Viatris, for trial funding from Endomag, Exact Sciences and institutional fees from AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, pfm medical, Roche, RTI Surgical., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Introduction: The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases., Methods: The impact of AKT1-knockout (AKT1&#95;KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1&#95;KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed., Results: Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1&#95;KO clones. RNAseq-analysis revealed the deregulation of CTSO , CYBB , GPR68 , CEBPA , ID1 , ID4 , METTL15 , PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR., Discussion: Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases., Competing Interests: The authors declare that they have no conflict of interest concerning the presented analysis. IW received speaker´s honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Lilly, MSD, Novar-tis, Pierre Fabre, Pfizer, Roche, and Seagen. BS received speaker´s honoraria, travel grants and consultancy honoraria as well as institutional research support from Astra Zeneca, MSD, Pfizer, Roche, GSK, Clovis, Eisai and Ethicon. VM received speaker’s honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre; Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead; institutional research support from Novartis, Roche, Seagen, Genentech and travel grants from Roche, Pfizer, Daiichi Sankyo, Gilead. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kempska, Oliveira-Ferrer, Grottke, Qi, Alawi, Meyer, Borgmann, Hamester, Eylmann, Rossberg, Smit, Jücker, Laakmann, Witzel, Schmalfeldt, Müller and Legler.)

With abemaciclib (monarchE study) and olaparib (OlympiA study) gaining approval in the adjuvant treatment setting, a significant change in the standard of care for patients with early stage breast cancer has been established for some time now. Accordingly, some diverse developments are slowly being transferred from the metastatic to the adjuvant treatment setting. Recently, there have also been positive reports of the NATALEE study. Other clinical studies are currently investigating substances that are already established in the metastatic setting. These include, for example, the DESTINY Breast05 study with trastuzumab deruxtecan and the SASCIA study with sacituzumab govitecan. In this review paper, we summarize and place in context the latest developments over the past months., Competing Interests: Conflict of Interest B. A. received honoria and travel grants from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo and Pfizer. M. B.-P. received honoraria for lectures and advisory role from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and study support from Mammotome, Endomag and Merit Medical. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun and onkowissen.de for clinical research management and/or medical education activities. N. D. has received honoraria from MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen, Gilead, MCI Healthcare. P. A. F. reports personal fees from Novartis, grants from BioNTech, personal fees from Pfizer, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from Merck Sharp & Dohme, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. T. N. F. has participated on advisory boards for Amgen, Daiichi Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi Sankyo, Roche, Novartis and Pfizer. A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal and Pfizer. N. H. received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. has received research Grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. H.-C. K. has received honoraria from Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo and MSD, travel support from Carl Zeiss, Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro and owns stock of Theraclion SA and Phaon Scientific GmbH. D. L. received honoraria from Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca, and Eisai. He is editorial board member of medactuell from medac. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Seagen, Pierre Fabre, MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca and travel support from Roche, Celgene and Pfizer. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. has participated on advisory boards for AstraZeneca, Clovis, Daiichi Sankyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen and Roche and has received honoraria for lectures from Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding by Exact Sciences and Endomag Manuscript support was done by Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. all honoraria went to the institution/employer: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi-Aventis, Novartis, Pierre Fabre, Seagen; Gilead. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. I. W. has participated on advisory boards for Novartis, Daiichi Sankyo, Lilly, Pfizer and received speaker honoraria from AstraZeneca, Daiichi-Sankyo, MSD, Novartis, Pfizer, Roche. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Celgene. R. W. has received honoraria, travel support from Agendia, Amgen, Aristo, AstraZeneca, Boehringer Ingelheim, Carl Zeiss, Meditec, Celgene, Daiichi Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, GlaxoSmithKline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi, Genzyme, Seagen, Tesaro Bio, Teva, Veracyte, Viatris. R. B. discloses advisory roles for AstraZeneca, Daiichi Sankyo, Eisai, Eli-Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen; lecture honoraria for AstraZeneca, Daiichi Sankyo, Eisai, Eli-Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; research support for Daiichi Sankyo, MSD, Novartis, Roche. C. K. L. reports stock by Theraklion and Phaon Scientific (self and family), honoraria by Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, SonoScape (self) and Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva Pharmaceuticals Industries, Theraklion, Janssen-Cilag, GlaxoSmithKline, LIV Pharma (family), Consulting to Roche, Novartis, Pfizer, Celgene, Phaon Scientific (self) and Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen (family); research funding by Roche, Novartis, Pfizer (self) as well as Travel and Accommodation by Roche, Daiichi Sankyo, Novartis (self) and Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo (family). J. E. has received consulting fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and Tesaro; contracted research from Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, Roche, and Odonate; and travel support from AstraZeneca, Daiichi Sankyo, Celgene, Pfizer, Novartis, Lilly, and Tesaro. F.-A. T. has received honoraria from GSK, Hexal, MSD, Novartis, Pfizer, Roche and Tesaro and travel expenses from GSK. The other authors have no conflict of interest to declare for this specific work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

In recent years, a number of new therapies have led to advances in the treatment of patients with advanced breast carcinoma. These substances are mainly CDK4/6 inhibitors and other substances that can overcome endocrine resistance, oral selective estrogen receptor degraders, antibody drug conjugates (ADCs), and PARP inhibitors. This review summarizes and evaluates the latest study results that have been published in recent months. This includes the overall survival data of the Destiny-Breast03 study, the first analysis of the CAPItello-291 study, the comparison of CDK4/6 inhibitor treatment with chemotherapy in the first line of therapy (RIGHT Choice study), the first analysis of the Destiny-Breast02 study in the treatment setting after T-DM1 treatment, and the first analysis of the Serena-2 study. Most of these studies have the potential to significantly change the therapeutic landscape for patients with advanced breast carcinoma and show that the continued rapid development of new therapies is always producing new results., Competing Interests: Conflict of Interest B. A. received honoria and travel grants from AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo and Pfizer. M. B.-P. received honoraria for lectures and advisory role from Roche, Novartis, Pfizer, pfm, Eli Lilly, Onkowissen, Seagen, Eisai, AstraZeneca, Amgen, Samsung, MSD, GSK, Daiichi Sankyo, Gilead, Sirius Pintuition, Pierre Fabre, and study support from Mammotome, Endomag and Merit Medical. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, BBraun and onkowissen.de for clinical research management and/or medical education activities. N. D. has received honoraria from MSD, Roche, AstraZeneca, Teva, Pfizer, Novartis, Seagen, Gilead, MCI Healthcare. P. A. F. reports personal fees from Novartis, grants from Biontech, personal fees from Pfizer, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, personal fees from Eisai, personal fees from Merck Sharp & Dohme, grants from Cepheid, personal fees from Lilly, personal fees from Pierre Fabre, personal fees from SeaGen, personal fees from Roche, personal fees from Hexal, personal fees from Agendia, personal fees from Gilead. T. N. F. has participated on advisory boards for Amgen, Daiichi Sankyo, Novartis, Pfizer, and Roche and has received honoraria for lectures from Amgen, Celgene, Daiichi Sankyo, Roche, Novartis and Pfizer. A. D. H. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Daiichi Sankyo, Hexal and Pfizer. N. H. received honoraria for lectures and/or consulting from Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen. W. J. has received research Grants and/or honoraria from Sanofi-Aventis, Daiichi Sankyo, Novartis, Roche, Pfizer, Lilly, AstraZeneca, Chugai, GSK, Eisai, Cellgene and Johnson & Johnson. H.-C. K. has received honoraria from Pfizer, Seagen, Novartis, Roche, Genomic Health/Exact Sciences, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva, Theraclion, Janssen-Cilag, GSK, LIV Pharma, Lilly, SurgVision, Onkowissen, Gilead, Daiichi Sankyo and MSD, travel support from Carl Zeiss, Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro and owns stock of Theraclion SA and Phaon Scientific GmbH. D. L. received honoraria from Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar and Roche and has received honoraria for lectures from MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, Gilead, AstraZeneca, and Eisai. He is editorial board member of medactuell from medac. V. M. received speaker honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead. Consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi Sankyo, Eisai, Lilly, Sanofi, Seagen, Gilead. Institutional research support from Novartis, Roche, Seagen, Genentech. Travel grants: Roche, Pfizer, Daiichi Sankyo. E. S. received honoraria from Roche, Celgene, AstraZeneca, Novartis, Pfizer, Tesaro, Aurikamed GmbH, Pfizer, Seagen, Pierre Fabre , MCI Deutschland GmbH, bsh medical communications GmbH, Onkowissen TV. A. S. received research grants from Celgene, Roche, honoraria from Amgen, AstraZeneca, Aurikamed, Bayer, Celgene, Clinsol, Connectmedica, Gilead, GSK, I-MED, Lilly, MCI Deutschland, Metaplan, MSD, Nanostring, Novartis, Onkowissen.de, Promedicis, Pfizer, Pierre Fabre, Roche, Seagen, Streamedup, Teva, Tesaro, Thieme and travel support from Celgene, Pfizer, Roche. F. S. participated on advisory boards for Novartis, Lilly, Amgen and Roche and received honoraria for lectures from Roche, AstraZeneca, MSD, Novartis and Pfizer. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca and travel support from Roche, Celgene and Pfizer. C. T. received honoraria for advisory boards and lectures from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Gilead, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen, Vifor. M. T. has participated on advisory boards for AstraZeneca, Clovis, Daiichi Sanyo, Eisai, Gilead Science, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen and Roche and has received honoraria for lectures from Amgen, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding by Exact Sciences and Endomag Manuscript support was done by Amgen, ClearCut, pfm medical, Roche, Servier, Vifor. M. U. all honoraria went to the institution/employer: Abbvie, Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Myriad Genetics, Pfizer, Roche, Sanofi-Aventis, Novartis, Pierre Fabre, Seagen; Gilead. M. W. has participated on advisory boards for AstraZeneca, Lilly, MSD, Novartis, Pfizer and Roche. I. W. has participated on advisory boards for Novartis, Daiichi Sankyo, Lilly, Pfizer and received speaker honoraria from AstraZeneca, Daiichi Sankyo, MSD, Novartis, Pfizer, Roche. A. W. participated on advisory boards for Novartis, Lilly, Amgen, Pfizer, Roche, Tesaro, Eisai and received honoraria for lectures from Novartis, Pfizer, Aurikamed, Roche, Celgene. R. W. has received honoraria, travel support from Agendia, Amgen, Aristo, AstraZeneca, Boehringer Ingelheim, Carl Zeiss, Meditec, Celgene, Daiichi Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, Puma Biotechnology, Riemser, Roche, Sandoz/Hexal, Sanofi, Genzyme, Seagen, Tesaro Bio, Teva, Veracyte, Viatris. R. B. discloses advisory roles for AstraZeneca, Daiichi Sankyo, Eisai, Eli-Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen; lecture honoraria for AstraZeneca, Daiichi Sankyo, Eisai, Eli-Lilly, Gilead, Grünenthal, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; research support for Daiichi Sankyo, MSD, Novartis, Roche. C. K.-L. reports stock by Theraklion and Phaon Scientific (self and family), honoraria by Roche, AstraZeneca, Celgene, Novartis, Pfizer, Lilly, Hexal, Amgen, SonoScape (self) and Genomic Health, Amgen, AstraZeneca, Riemser, Carl Zeiss Meditec, Teva Pharmaceuticals Industries, Theraklion, Janssen-Cilag, GlaxoSmithKline, LIV Pharma (family), Consulting to Roche, Novartis, Pfizer, Celgene, Phaon Scientific (self) and Pfizer, Novartis, SurgVision, Carl Zeiss Meditec, Amgen, Onkowissen (family); research funding by Roche, Novartis, Pfizer (self) as well as Travel and Accommodation by Roche, Daiichi Sankyo, Novartis (self) and Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo (family). J. E. has received consulting fees from AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Pierre Fabre, Roche, and Tesaro; contracted research from Daiichi Sankyo, Pfizer, Lilly, Novartis, Seattle Genetics, AstraZeneca, Roche, and Odonate; and travel support from AstraZeneca, Daiichi Sankyo, Celgene, Pfizer, Novartis, Lilly, and Tesaro. F.-A. T. has received honoraria from GSK, Hexal, MSD, Novartis, Pfizer, Roche and Tesaro and travel expenses from GSK. The other authors have no conflict of interest to declare for this specific work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Up to 30% of metastatic breast cancer (BC) patients develop brain metastases (BM). Prognosis of patients with BM is poor and long-term survival is rare. Identification of factors associated with long-term survival is important for improving treatment modalities., Patients and Methods: A total of 2889 patients of the national registry for BM in BC (BMBC) were available for this analysis. Long-term survival was defined as overall survival (OS) in the upper third of the failure curve resulting in a cut-off of 15 months. A total of 887 patients were categorized as long-term survivors., Results: Long-term survivors compared to other patients were younger at BC and BM diagnosis (median 48 versus 54 years and 53 versus 59 years), more often had HER2-positive tumors (59.1% versus 36.3%), less frequently luminal-like (29.1% versus 35.7%) or triple-negative breast cancer (TNBC) (11.9% versus 28.1%), showed better Eastern Cooperative Oncology Group (ECOG) performance status (PS) at the time of BM diagnosis (ECOG 0-1, 76.9% versus 51.0%), higher pathological complete remission rates after neoadjuvant chemotherapy (21.6% versus 13.7%) and lower number of BM (n = 1, BM 40.9% versus 25.4%; n = 2-3, BM 26.5% versus 26.7%; n ≥4, BM 32.6% versus 47.9%) (P < 0.001). Long-term survivors had leptomeningeal metastases (10.4% versus 17.5%) and extracranial metastases (ECM, 73.6% versus 82.5%) less frequently, and asymptomatic BM more often at the time of BM diagnosis (26.5% versus 20.1%), (P < 0.001). Median OS in long-term survivors was about two times higher than the cut-off of 15 months: 30.9 months [interquartile range (IQR) 30.3] overall, 33.9 months (IQR 37.1) in HER2-positive, 26.9 months (IQR 22.0) in luminal-like and 26.5 months (IQR 18.2) in TNBC patients., Conclusions: In our analysis, long-term survival of BC patients with BM was associated with better ECOG PS, younger age, HER2-positive subtype, lower number of BM and less extended visceral metastases. Patients with these clinical features might be more eligible for extended local brain and systemic treatment., Competing Interests: Disclosure IW received speaker’s honoraria from Astra Zeneca, Merck, Pfizer, Roche, Daiichi-Sankyo, Seagen, Gilead and Novartis. KL received speaker’s honoraria from Roche, Novartis, Pfizer, Exact Sciences, MSD, Eisai, Lilly, Seagen, AstraZeneca and Daiichy Sankyo. MS has received personal fees from AstraZeneca, BioNTech, Daiichi-Sankyo, Eisai, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and Seagen. His institution has received research funding from AstraZeneca, BioNTech, Eisai, Genentech, German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pierre Fabre and Seagen. In addition, he has a patent for EP 2390370 B1 and a patent for EP 2951317 B1 issued. SL reports grants, non-financial support and other from Daiichi-Sankyo, during the conduct of the study; grants and other from Abbvie, other from Amgen, grants and other from AstraZeneca, other from BMS, grants and other from Celgene, other from Eirgenix, other from Eisai Europe Ltd, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants from Molecular Health, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Relay Therapeutics, grants, non-financial support and other from Roche, other from Sanofi, non-financial support and other from Seagen, other from Olema Pharmaceutics, outside the submitted work; In addition, SL has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending and a patent Digital Ki67 Evaluator with royalties paid. CD reports advisory role for MSD Oncology, Daiichi-Sankyo, Molecular Health, AstraZeneca, Roche and Lilly; CD received research funding from Myriad Genetics, Roche and German Breast Group; CD owns following patents: VMScope digital pathology software, Patent WO2020109570A1, Patent WO2015114146A1, Patent WO2010076322A1. MT received personal fees from Agendia, Amgen, Art tempi, AstraZeneca, Aurikamed, Celgene, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Hexal, Lilly, MSD, Novartis, Onkowissen, Organon, Pfizer, Pierre Fabre, Roche, Seagen, Servier, Streamd Up!, Viatris, Vifor, trial funding from Exact Science and institutional trial honoraria from AstraZeneca, Celgene, Novartis, Roche. VM received speaker honoraria from Amgen, Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead and Pierre Fabre; consultancy honoraria from Hexal, Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Lilly, Sanofi, Seagen and Gilead; Institutional research support from Novartis, Roche, Seagen, Genentech; travel grants: Roche, Pfizer, Daiichi-Sankyo, Gilead. RW received support for advisory, consultancy, speaker and travel grants from Agendia, Amgen, Aristo, AstraZeneca, Boeringer Ingelheim, Carl Zeiss, Celgene, Clinsol, Clovis Oncology, Daiichi-Sankyo, Eisai, Exact Sciences, Genomic Health, Gilead, Glaxo Smith Kline, Hexal, Lilly, Medstrom Medical, MSD, Mundipharma, Mylan, Nanostring, Novartis, Odonate, Paxman, Palleos, Pfizer, Pierre Fabre, PINK, PumaBiotechnolgogy, Riemser, Roche, Sandoz/Hexal, Sanofi Genzyme, Seattle Genetics /Seagen, Stemline, Tesaro Bio, Teva, Veracyte and Viatris. TD received Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novartis, IOMEDICO and participated on a Data Safety Monitoring Board or Advisory Board for Novartis, IOMEDICO. All other authors have declared no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 -) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients' satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician-patient interaction., Methods: PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 - MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS)., Discussion: The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = "Deterioration of quality of life" (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform). EudraCT Number: 2016-004191-22., (© 2023. The Author(s).)

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis., Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19-78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression., Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes ( BRCA1 : n = 170 [10.6%]; BRCA2 : n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years ( n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21-1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years., Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed., Competing Interests: Christopher Schröder reports an institutional grant from Illumina and research grants from BMS Stiftung Immunonkologie outside the submitted work. Julia Gallwas is a member of the academic advisory board of the Bundesaerztekammer and was paid for lectures for Merck Sharp & Dohme and Roche Diagnostics between 2017 and 2019. All other authors have no conflicts to declare., (Copyright © 2023 by The Author(s). Published by S. Karger AG, Basel.)

iKNOW is the first evidence-based digital tool to support personalized counseling for women in Germany with a hereditary cancer risk. The counseling tool is designed for carriers of pathogenic gBRCA (germline breast cancer gene) variants that increase the lifetime risk of breast and ovarian cancer. Carriers of pathogenic variants are confronted with complex, individualized risk information, and physicians must be able to convey this information in a comprehensible way to enable preference-sensitive health decisions. In this paper, we elaborate on the clinical, regulatory, and practical premises of personalized counseling in Germany. By operationalizing these premises, we formulate 5 design principles that, we suggest, are specific enough to develop a digital tool (eg, iKNOW), yet wide-ranging enough to inform the development of counseling tools for personalized medicine more generally: (1) digital counseling tools should implement the current standard of care (eg, based on guidelines); (2) digital counseling tools should help to both standardize and personalize the counseling process (eg, by enabling the preference-sensitive selection of counseling contents from a common information base); (3) digital counseling tools should make complex information easy to access both cognitively (eg, by using evidenced-based risk communication formats) and technically (eg, by means of responsive design for various devices); (4) digital counseling tools should respect the counselee's data privacy rights (eg, through strict pseudonymization and opt-in consent); and (5) digital counseling tools should be systematically and iteratively evaluated with the users in mind (eg, using formative prototype testing to ensure a user-centric design and a summative multicenter, randomized controlled trial). On the basis of these paradigmatic design principles, we hope that iKNOW can serve as a blueprint for the development of more digital innovations to support personalized counseling approaches in cancer medicine., (©Dorothee Speiser, Maren Heibges, Laura Besch, Caren Hilger, Marie Keinert, Katharina Klein, Gudrun Rauwolf, Christine Schmid, Sven Schulz-Niethammer, Steffi Stegen, Viola Westfal, Isabell Witzel, Benedikt Zang, Friederike Kendel, Markus A Feufel. Originally published in JMIR Formative Research (https://formative.jmir.org), 21.04.2023.)