Alexander Hein1, Andreas D Hartkopf2, Julius Emons1, Michael P Lux3, Bernhard Volz4, Florin-Andrei Taran5, Friedrich Overkamp6, Peyman Hadji7, Hans Tesch8, Lothar Häberle9, Johannes Ettl10, Diana Lüftner11, Lena A Wurmthaler1, Markus Wallwiener12, Volkmar Müller13, Matthias W Beckmann1, Erik Belleville14, Pauline Wimberger15, Carsten Hielscher16, Christian M Kurbacher17, Rachel Wuerstlein18, Christoph Thomssen19, Michael Untch20, Peter A Fasching21, Wolfgang Janni22, Tanja N Fehm23, Diethelm Wallwiener2, Sara Y Brucker2, Andreas Schneeweiss24, Hans-Christian Kolberg25. 1. Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany. 2. Department of Obstetrics and Gynecology, University of Tübingen, Tübingen, Germany. 3. Department of Gynecology and Obstetrics, Frauenklinik St. Louise, St. Josefs-Krankenhaus, Salzkotten, Kooperatives Brustzentrum Paderborn, Paderborn, Germany; Kooperatives Brustzentrum Paderborn, Paderborn, Germany. 4. Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany; Ansbach University of Applied Sciences, Ansbach, Germany. 5. Department of Obstetrics and Gynecology, University Hospital Freiburg, Freiburg im Breisgau, Germany. 6. OncoConsult Overkamp GmbH, Berlin, Germany. 7. Frankfurt Center of Bone Health, Frankfurt am Main, Germany. 8. Oncology Practice at Bethanien Hospital, Frankfurt am Main, Germany. 9. Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany; Biostatistics Unit, Department of Gynecology and Obstetrics, Erlangen University Hospital, Erlangen, Germany. 10. Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 11. Department of Hematology, Oncology and Tumor Immunology, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany. 12. Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg, Germany. 13. Department of Gynecology, Hamburg-Eppendorf University Medical Center, Hamburg, Germany. 14. ClinSol GmbH & Co KG, Würzburg, Germany. 15. Department of Gynecology and Obstetrics, Carl Gustav Carus Faculty of Medicine and University Hospital, Technical University of Dresden, Dresden, Germany; National Center for Tumor Diseases (NCT), Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; Carl Gustav Carus Faculty of Medicine and University Hospital, Technical University of Dresden, Dresden, Germany; Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany; German Cancer Consortium (DKTK), Dresden, Germany. 16. gSUND Gynäkologie Kompetenzzentrum Stralsund, Stralsund, Germany. 17. Gynäkologie I (Gynäkologische Onkologie), Gynäkologisches Zentrum Bonn-Friedensplatz, Bonn, Germany. 18. Department of Gynecology and Obstetrics, Breast Center and CCC Munich, LMU University Hospital Munich, Munich, Germany. 19. Department of Gynecology, Martin Luther University of Halle-Wittenberg, Halle (Saale), Germany. 20. Department of Gynecology and Obstetrics, Helios Clinic Berlin Buch, Berlin, Germany. 21. Department of Gynecology and Obstetrics, Erlangen University Hospital, Comprehensive Cancer Center Erlangen-EMN, Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany. Electronic address: peter.fasching@uk-erlangen.de. 22. Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany. 23. Department of Gynecology and Obstetrics, Düsseldorf University Hospital, Düsseldorf, Germany. 24. National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg. 25. Department of Gynecology and Obstetrics, Marienhospital Bottrop, Bottrop, Germany.
Abstract
PURPOSE: Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. METHODS: PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). RESULTS: Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12-4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor-positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. CONCLUSIONS: We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.
PURPOSE: Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. METHODS: PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). RESULTS: Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12-4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor-positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. CONCLUSIONS: We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.
Authors: Simon Peter Gampenrieder; Gabriel Rinnerthaler; Christoph Tinchon; Andreas Petzer; Marija Balic; Sonja Heibl; Clemens Schmitt; August Felix Zabernigg; Daniel Egle; Margit Sandholzer; Christian Fridolin Singer; Florian Roitner; Christopher Hager; Johannes Andel; Michael Hubalek; Michael Knauer; Richard Greil Journal: Breast Cancer Res Date: 2021-12-14 Impact factor: 6.466
Authors: Bahriye Aktas; Tanja N Fehm; Manfred Welslau; Volkmar Müller; Diana Lüftner; Florian Schütz; Peter A Fasching; Wolfgang Janni; Christoph Thomssen; Isabell Witzel; Erik Belleville; Michael Untch; Marc Thill; Hans Tesch; Nina Ditsch; Michael P Lux; Maggie Banys-Paluchowski; Cornelia Kolberg-Liedtke; Andreas D Hartkopf; Achim Wöckel; Hans-Christian Kolberg; Elmar Stickeler; Nadia Harbeck; Andreas Schneeweiss Journal: Geburtshilfe Frauenheilkd Date: 2022-09-13 Impact factor: 2.754