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High-level synthesis (HLS) is utilized for high-performance and energy-efficient heterogeneous systems designing. HLS is assist in field-programmable gate array circuits designing where hardware implementations are refined and replaced in target device. However, the power-process-voltage-temperature-delay (PPVTD) variation in VLSI circuits undergoes many problems and reduced the performance. In order to address these problems, C4.5 with eXtreme Gradient Boosting Classification based High Level Synthesis (C4.5-XGBCHLS) Method is designed for afford better runtime adaptability (RA) with minimal error rate. VLSI circuits are designed using the behavioral input and results are measured at running condition. When VLSI circuit’s results get reduced, the language description of the circuit is considered as an input. Then, compilation process convert high level specification into Intermediate Representation (IR) in control/data flow graph (CDFG). CDFG computes data and control dependencies among operations. eXtreme Gradient Boosting (XGBoost) Classifier is exploited in C4.5-XGBCHLS method to classify the error causing functional unit (FU) with minimal error rate. XGBoost Classifier exploited C4.5 decision tree as base classifier to enhance classification of error causing FU in VLSI circuits. After that, FU gets allocated in place of error causing FU from functional library based on the design objectives and PPVTD variations. Finally, operation scheduling and binding process is executed for register transfer level (RTL) generation to form VLSI circuits with improved RA. The simulation results shows that the C4.5-XGBCHLS method enhances the performance of functional unit selection accuracy (FUSA) with minimal error rate (ER) and circuit adaptability time (CAT).

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/ ).)

In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy. Around 70 - 80% of patients are treated with a CDK4/6i. In recent years, a number of biomarkers associated with progression, clonal selection or evolution have been reported for CDK4/6i and their endocrine combination partners. Understanding the mechanisms behind treatment efficacy and resistance is important. A better understanding could contribute to planning the most effective therapeutic sequences and utilizing basic molecular information to overcome endocrine resistance. One study with large numbers of patients which aims to elucidate these mechanisms is the Comprehensive Analysis of sPatial, TempORal and molecular patterns of ribociclib efficacy and resistance in advanced Breast Cancer patients (CAPTOR BC) trial. This overview summarizes the latest clinical research on resistance to endocrine therapies, focusing on CDK4/6 inhibitors and discussing current study concepts., 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, Onkowissen, Daiichi Sankyo and Pfizer. C. B. is an employee of Novartis Deutschland GmbH. E. B. received honoraria from Gilead, Ipsen, Sanofi, Sandoz, SunPharma, AstraZeneca, Novartis, Hexal, BMS, Lilly, Pfizer, Roche, MSD, B Braun and onkowissen.de for clinical research management and/or medical education activities. S. Y. B. has received honoraria from Roche, Novartis, Pfizer, MSD, Teva, AstraZeneca. 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. E. has received honoraria from AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, GSK, MSD, Novartis, Pfizer, Roche, Stemline. 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. C. C. H. has received honoraria from Pfizer, Novartis, Roche, AstraZeneca, Eisai and Daiichi Sankyo. H. H. received speaker honoraria from Novartis. H. N. 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, Novartis, Seagen, 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, 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. 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. B. R. reports research grants from Roche, Menarini, Lilly, Inivata. Honoraria from AZ, Roche. C. R. is an employee of Novartis Deutschland GmbH. 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. K. S. received travel support from Gilead and Lilly. F.-A. T. received speaker and consultancy honoraria from AstraZeneca, Genomic Health, Gilead, GSK, Hexal, MSD, Novartis, Onkowissen, Pfizer, Roche, Tesaro. H. T. received honoraria from Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca and travel support from Roche, Celgene, and Pfizer. M. T. has participated on advisory boards for AstraZeneca, Celgene, Clovis, Daiichi Sankyo, Eisai, Gilead Science, Grünenthal, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen, and Roche and has received honoraria for lectures from Amgen, Aurikamed, Celgene, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor and AstraZeneca and has received trial funding from Exact Sciences and Endomag Manuscript support was provided 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. P. W. has received honoraria from Roche, Novartis, Amgen, AstraZeneca, Pfizer, MSD, Clovis, Tesaro, Celgene, Teva, Eisai, Daiichi Sankyo, Seagen and Eli Lilly. The other authors (L. L. V, M. R., S. H., V. T., I. J.-B., D. A., M. B., M. S., J. R., I. N.) have no conflict of interest to declare for this specific work./ B. A. erhielt Honorare und Reisekosten von AstraZeneca, Gilead, Genomic Health, Roche, Novartis, Celgene, Lilly, MSD, Eisai, Teva, Tesaro, Onkowissen, Daiichi Sankyo und Pfizer. C. B. ist Angestellte der Firma Novartis Deutschland GmbH. 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 Aktivitäten der medizinischen Fortbildung. S. Y. B. erhielt Honorare von Roche, Novartis, Pfizer, MSD, Teva, AstraZeneca. 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 finanzieller Unterstützung von Novartis und BioNtech. T. E. erhielt Honorare von AstraZeneca, Eli Lilly, Daiichi Sankyo, Gilead, GSK, MSD, Novartis, Pfizer, Roche, Stemline. T. N. F. hat in Beiräten mitgewirkt für Amgen, Daiichi Sankyo, Novartis, Pfizer und Roche und hat Vortragshonorare erhalten 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. C. C. H. erhielt Honorare von Pfizer, Novartis, Roche, AstraZeneca, Eisai und Daiichi Sankyo. H. H. erhielt Sprecherhonorare von Novartis. H. N. erhielt Vortragshonorare und/oder Honorare für Beratertätigkeiten vn Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Gilead, Lilly, MSD, Mylan, 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. H.-C. K. erhielt Honorare von Pfizer, Novartis, Seagen, 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, Reisekostenzuschüsse von Carl Zeiss Meditec, LIV Pharma, Novartis, Amgen, Pfizer, Daiichi Sankyo, Tesaro und besitzt Aktien von Theraclion SA und Phaon Scientific GmbH. D. L. erhielt Honorare von Amgen, AstraZeneca, Eli Lilly, High5md, Gilead, GSK, Loreal, MSD, Novartis, Onkowissen, Pfizer, Seagen, Teva. M. P. L. hat in Beiräten mitgewirkt für AstraZeneca, Lilly, MSD, Novartis, Pfizer, Eisai, Gilead, Exact Sciences, Pierre Fabre, Grünenthal, Daiichi Sankyo, PharmaMar, Roche, SamanTree, Sysmex und Hexal und erhielt Vortragshonorare von MSD, Lilly, Roche, Novartis, Pfizer, Exact Sciences, Daiichi Sankyo, Grünenthal, pfm, Gilead, AstraZeneca und Eisai. 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. B. R. erhielt Forschungsstipendien von Roche, Menarini, Lilly, Inivata, Honorare von AZ, Roche. C. R. ist Angestellter der Firma Novartis Deutschland GmbH. 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. K. S. erhielt Reisekostenzuschüsse von Gilead und Lilly. F.-A. T. erhielt Sprecher- und Beraterhonorare von AstraZeneca, Genomic Health, Gilead, GSK, Hexal, MSD, Novartis, Onkowissen, Pfizer, Roche, Tesaro. H. T. erhielt Honorare von Novartis, Roche, Celgene, Teva, Pfizer, AstraZeneca und Reisekostenzuschüsse von Roche, Celgene und Pfizer. M. T. hat in Beiräten mitgewirkt für AstraZeneca, Celgene, Clovis, Daiichi Sankyo, Eisai, Gilead Science, Grünenthal, GSK, Lilly, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Seagen und Roche, erhielt Vortragshonorare von Amgen, Aurikamed, Celgene, Clovis, Daiichi Sankyo, Eisai, GSK, Lilly, MSD, Roche, Novartis, Organon, Pfizer, Seagen, Exact Sciences, Viatris, Vifor und AstraZeneca und erhielt Studienfinanzierung von Exact Sciences und 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. P. W. erhielt Honorare von Roche, Novartis, Amgen, AstraZeneca, Pfizer, MSD, Clovis, Tesaro, Celgene, Teva, Eisai, Daiichi Sankyo, Seagen und Eli Lilly. Die anderen Autoren und Autorinnen (L. L. V, M. R., S. H., V. T., I. J.-B., D. A., M. B., M. S., J. R., I. N.) 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/ ).)

Introduction: The negative impact of unmanaged psychological distress on quality of life and outcome in breast cancer survivors has been demonstrated. Fortunately, studies indicate that distress can effectively be addressed and even prevented using evidence-based interventions. In Germany prescription-based mobile health apps, known as DiGAs (digital health applications), that are fully reimbursed by health insurances, were introduced in 2020. In this study, the effectiveness of an approved breast cancer DiGA was investigated: The personalized coaching app PINK! Coach supports and accompanies breast cancer patients during therapy and follow-up., Methods: PINK! Coach was specifically designed for breast cancer (BC) patients from the day of diagnosis to the time of Follow-up (aftercare). The app offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT (DRKS00028699) was performed with n = 434 patients recruited in 7 German breast cancer centers from September 2022 until January 2023. Patients with BC were included independent of their stage of diseases, type of therapy and molecular characteristics of the tumor. Patients were randomized into one of two groups: The intervention group got access to PINK! over 12 weeks; the control group served as a waiting-list comparison to "standard of care." The primary endpoint was psychological distress objectified by means of Patient Health Questionnaire-9 (PHQ-9). Subgroups were defined to investigate the app's effect on several patient groups such as MBC vs. EBC patients, patients on therapy vs. in aftercare, patients who received a chemotherapy vs. patients who did not., Results: Efficacy analysis of the primary endpoint revealed a significant reduction in psychological distress (least squares estimate -1.62, 95% confidence interval [1.03; 2.21]; p<0.001) among intervention group patients from baseline to T3 vs, control group. Subgroup analysis also suggested improvements across all clinical situations., Conclusion: Patients with breast cancer suffer from psychological problems including anxiety and depression during and after therapy. Personalized, supportive care with the app PINK! Coach turned out as a promising opportunity to significantly improve psychological distress in a convenient, accessible, and low-threshold manner for breast cancer patients independent of their stage of disease (EBC/MBC), therapy phase (aftercare or therapy) or therapy itself (chemotherapy/other therapy options). The app is routinely available in Germany as a DiGA. Clinical Trial Registration: DRKS Trial Registry (DRKS00028699)., Competing Interests: Authors JW, SvS, PW, AS, and FH were employed by the company PINK!. Authors NH, MS, FB, and RW had a consulting contract with PINK!. 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 © 2024 Wolff, Seidel, Wuelfing, Lux, Eulenburg, Smollich, Baumann, Seitz, Kuemmel, Thill, Tio, Braun, Hollaender, Seitz, Horn, Harbeck and Wuerstlein.)

Purpose: This phase II study evaluated the impact of adding ribociclib to maintenance endocrine therapy (ET) treatment of physicians' choice following the first palliative chemotherapy in pre- and post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor 2 negative (HER2-) metastatic breast cancer (mBC)., Patients and Methods: The initial randomized study design was later amended into a single-arm study, and all subsequent patients received ribociclib and ET. The primary end point was locally assessed progression-free survival (PFS). Secondary end points included overall survival (OS), clinical benefit rate (CBR), safety, compliance, and quality of life (QoL)., Results: A total of 43 patients received ribociclib + ET and 10 patients received ET only. Median PFS was 12.4 months [95% CI 8.7-24.4] for patients who received ribociclib + ET and 4.75 months [95% CI 1.0-10.3] for those who received ET only. Median OS was not reached for patients who received ribociclib + ET, and 28 (65.1%) patients experienced clinical benefit [95% CI 49.1-79.0]. For patients who received ribociclib + ET, grade 3-4 hematological adverse events (AEs) occurred in 25 (58.1%) patients, and grade 3-4 non-hematological AEs occurred in 17 (39.5%) patients. During the study, 15 patients died - 14 of whom due to tumor-related reasons, and one patient due to pneumonia, which was not treatment-related., Conclusion: The results of the AMICA study show a promising efficacy and safety of maintenance treatment with ribociclib added to ET after at least stable disease following the first metastatic chemotherapy in patients with HR+/HER2-mBC., Trial Registration: Anti-hormonal Therapy With Ribociclib in HR-positive/HER2- Negative Metastatic Breast Cancer (AMICA), NCT03555877, https://clinicaltrials.gov/ct2/show/NCT03555877., 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. T. Decker reports ad boards from Lilly, Novartis, and IOMEDICO. K. Luedtke-Heckenkamp reports personal fees from AstraZeneca, Gilead, Novartis, and Pfizer. She is on the advisory board of Daiichi Sankyo, Lilly, and Roche. K. Lübbe is on the advisory board of Genomic Health, Roche, Daiichy Sankyo, Lilly, MSD, EISAI, Seagen, and Novartis, and has received lecture fees from Novartis, AstraZeneca, Genomic Health, Roche, and Lilly. M. Schmidt reports personal fees from AstraZeneca, personal fees from BioNTech, personal fees from Daiichi Sankyo, personal fees from Eisai, personal fees from Lilly, personal fees from MSD, personal fees from Novartis, personal fees from Pfizer, personal fees from Pierre-Fabre, personal fees from Roche, and personal fees from SeaGen outside the submitted work; in addition, M. Schmidt has a patent for EP 2390370 B1: A method for predicting the response of a tumor in a patient suffering from or at risk of developing recurrent gynecologic cancer towards a chemotherapeutic agent issued and a patent for EP 2951317 B1: A method for predicting the benefit from inclusion of a taxane in a chemotherapy regimen in patients with breast cancer issued. C. Denkert reports grants from European Commission H2020, grants from German Cancer Aid Translational Oncology, grants from German Breast Group; personal fees from Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Lilly, Molecular Health, Merck, grants from Myriad to his institution, other from Sividon diagnostics (cofounder and former shareholder until 2016); In addition, C. Denkert has a patent VMScope digital pathology software with royalties paid, a patent WO2020109570A1 - cancer immunotherapy pending, and a patent WO2015114146A1 and WO2010076322A1- therapy response issued. V. Müller 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, and Genentech; and travel grants from Roche, Pfizer, Daiichi Sankyo, and Gilead. M. Thill is on the advisory boards of 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. He has received support from Amgen, AstraZeneca, Celgene, ClearCut, Clovis, Daiichi Sanyko, Hexal, Neodynamics, Novartis, Pfizer, pfm medical, Roche, Servier, and Sirius Medical. He reports travels expenses from Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Hexal, I-Med-Institute, Lilly, MCI, Medtronic, MSD, Neodynamics, Norgine, Novartis, Pfizer, pfm Medical, Roche, RTI Surgical, and Seagen. He has received honoraria and funding from Amgen, Art Tempi, AstraZeneca, Biom’Up, Celgene, Clearcut, Clovis, Connect Medica, Eisai, Endomag, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, MCI, Medscape, MSD, Medtronic, Neodynamics, Novartis, Onkowissen, Pfizer, pfm medical, Roche, RTI Surgical, Seagen, StreamedUp, Sysmex, Vifor, and Viatris. N. Hirmas and N. Filmann declare to be GBG Forschungs GmbH employees. GBG Forschungs GmbH received funding for research grants from Abbvie, AstraZeneca, BMS, Daiichi-Sankyo, Gilead, Novartis, Pfizer, and Roche (paid to the institution); other (non-financial/medical writing) from Daiichi-Sankyo, Gilead, Novartis, Pfizer, Roche and Seagen (paid to the institution). GBG Forschungs GmbH has following royalties/patents: EP14153692.0, EP21152186.9, EP15702464.7, EP19808852.8 and VM Scope GmbH. S. Loibl reports grants or contracts paid to institute from Abbvie, AstraZeneca, DSI, Celgene, Gilead, Novartis, Pfizer, Roche, Molecular H; in addition, S. Loibl has royalties or licenses for Digital Ki67 Evaluator from VM Scope GmbH that were paid to institute; in addition, S. Loibl receives honorary for lectures paid to the institute from AstraZeneca, DSI, Gilead, Novartis, Pfizer, and Roche; non-financial for Medical Writing from DSI, Gilead, Novartis, Pfizer, Roche, and Seagen; in addition, S. Loibl has patent for EP14153692.0, EP21152186.9, EP15702464.7 and EP19808852.8, all patents via institute; in addition, S. Loibl declares participation on a Data Safety Monitoring Board or Advisory Board from Abbvie, Amgen, AstraZeneca, BMS, Celgene, DSI, Eirgenix, Eisai Europe, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Relay Therapeutics, Roche, Sanofi, and Seagen, all paid to institute., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel-based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m² weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published. In this study, we investigated whether receptor activator of nuclear factor-kappa B (RANK) expression, as part of the denosumab target pathway: (i) may retrospectively identify a subgroup of patients with additional clinical benefit of denosumab or (ii) may predict response to nab-paclitaxel NACT., Experimental Design: RANK protein was IHC-stained on pre-therapeutic core biopsies from patients of the GeparX study (n = 667) with the antibody RANK/Envision System HRP (DAB) and was analyzed for the percentage of membranous RANK tumor cell staining (>5% RANKhigh vs. ≤5% RANKlow)., Results: We could not identify any patient subgroup with differential response under denosumab add-on treatment in patients with RANKhigh expression [139/667, 20.8%; OR, 0.86; 95% confidence interval (CI), 0.44-1.68; P = 0.667] or RANKlow expression (528/667 (79.2%) OR, 1.10; 95% CI, 0.78-1.56; P = 0.589; Pinteraction = 0.528). However, the pCR rate was higher in the RANKhigh subgroup compared with RANKlow (50% vs. 39%; OR, 1.52; 95% CI, 1.04-2.21; P = 0.037). RANK expression constituted an independent predictor of response to NACT frequently in patients with luminal-like subtype (HR+/HER2-; OR, 2.98; 95% CI, 1.30-6.79; P = 0.010). No predictive value of RANK expression among the different nab-paclitaxel regimens was observed., Conclusion: We report RANK expression to be an independent predictive biomarker for response to NACT in patients with luminal-like breast cancer., (©2023 American Association for Cancer Research.)

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/ ).)

Immune checkpoint blockade (ICB) benefits some patients with triple-negative breast cancer, but what distinguishes responders from non-responders is unclear 1 . Because ICB targets cell-cell interactions 2 , we investigated the impact of multicellular spatial organization on response, and explored how ICB remodels the tumour microenvironment. We show that cell phenotype, activation state and spatial location are intimately linked, influence ICB effect and differ in sensitive versus resistant tumours early on-treatment. We used imaging mass cytometry 3 to profile the in situ expression of 43 proteins in tumours from patients in a randomized trial of neoadjuvant ICB, sampled at three timepoints (baseline, n = 243; early on-treatment, n = 207; post-treatment, n = 210). Multivariate modelling showed that the fractions of proliferating CD8 + TCF1 + T cells and MHCII + cancer cells were dominant predictors of response, followed by cancer-immune interactions with B cells and granzyme B + T cells. On-treatment, responsive tumours contained abundant granzyme B + T cells, whereas resistant tumours were characterized by CD15 + cancer cells. Response was best predicted by combining tissue features before and on-treatment, pointing to a role for early biopsies in guiding adaptive therapy. Our findings show that multicellular spatial organization is a major determinant of ICB effect and suggest that its systematic enumeration in situ could help realize precision immuno-oncology., (© 2023. The Author(s).)

Background: Although biosimilar uptake has increased (at a variable pace) in many countries, there have been recent concerns about the long-term sustainability of biosimilar markets. The aim of this manuscript is to assess the sustainability of policies across the biosimilar life cycle in selected countries with a view to propose recommendations for supporting biosimilar sustainability. Methods: The study conducted a comparative analysis across 17 countries from North America, South America, Asia-Pacific, Europe and the Gulf Cooperation Council. Biosimilar policies were identified and their sustainability was assessed based on country-specific reviews of the scientific and grey literature, validation by industry experts and 23 international and local non-industry experts, and two advisory board meetings with these non-industry experts. Results: Given that European countries tend to have more experience with biosimilars and more developed policy frameworks, they generally have higher sustainability scores than the other selected countries. Existing approaches to biosimilar manufacturing and R&D, policies guaranteeing safe and high-quality biosimilars, exemption from the requirement to apply health technology assessment to biosimilars, and initiatives counteracting biosimilar misconceptions are considered sustainable. However, biosimilar contracting approaches, biosimilar education and understanding can be ameliorated in all selected countries. Also, similar policies are sometimes perceived to be sustainable in some markets, but not in others. More generally, the sustainability of the biosimilar landscape depends on the nature of the healthcare system and existing pharmaceutical market access policies, the experience with biosimilar use and policies. This suggests that a general biosimilar policy toolkit that ensures sustainability does not exist, but varies from country to country. Conclusion: This study proposes a set of elements that should underpin sustainable biosimilar policy development over time in a country. At first, biosimilar policies should guarantee the safety and quality of biosimilars, healthy levels of supply and a level of cost savings. As a country gains experience with biosimilars, policies need to optimise uptake and combat any misconceptions about biosimilars. Finally, a country should implement biosimilar policies that foster competition, expand treatment options and ensure a sustainable market environment., Competing Interests: GC-H has received consultancy and speaker fees from AbbVie, Amgen, Janssen-Cilag, Libbs, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB. OM and GH work at Nile, secretary general of the French think tank “Biosimilaires” and have links of interest with Accord Healthcare, Amgen, Biogen, and Sandoz. MT has received personal honoraria for lectures and participation in advisory boards from Amgen, Medscape, Jörg Eickeler, Onkowissen, Organon, Pfizer, Viatris, Vifor. He received manuscript support by Amgen, Roche, Servier and travel expenses by Amgen, Hexal, I-Med-Institute, Pfizer, Roche. Congress support was given by Amgen, Hexal, Pfizer, Roche. TW, MP, and RS were commissioned to support the project that informed this analysis and they assume editorial responsibility as contributors to the study. Charles River Associates is an economic consultancy company. SS is one of the founding members of the KU Leuven Fund on Market Analysis of Biologics and Biosimilars following Loss of Exclusivity (MABEL Fund). SS was involved in a stakeholder roundtable on biologics and biosimilars sponsored by Amgen, Pfizer and MSD, and he has participated in advisory board meetings for Amgen, Pfizer, Organon and Sandoz. He has contributed to studies on biologics and biosimilars for Hospira, Celltrion, Mundipharma and Pfizer; and he has had speaking engagements for Amgen, Celltrion, Organon and Sandoz. Author AB was employed by Matrix Global Advisors. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed., (Copyright © 2023 Alnaqbi, Bellanger, Brill, Castañeda-Hernández, Clopés Estela, Delgado Sánchez, García-Alfonso, Gyger, Heinrich, Hezard, Kakehasi, Koehn, Mariotte, Mennini, Mayra Pérez-Tapia, Pistollato, Saada, Sasaki, Tambassis, Thill, Werutsky, Wilsdon and Simoens.)

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.)

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.)

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/).)