Sonia L Villegas1, Valentina Nekljudova2, Nicole Pfarr3, Jutta Engel4, Michael Untch5, Simone Schrodi4, Frank Holms6, Hans U Ulmer7, Peter A Fasching8, Karsten E Weber2, Christian Albig3, Clemens Heinrichs9, Frederik Marmé10, Arndt Hartmann11, Claus Hanusch12, Wolfgang D Schmitt1, Jens Huober13, Bianca Lederer2, Marion van Mackelenbergh14, Hans Tesch15, Christian Jackisch16, Mahdi Rezai17, Peter Sinn18, Bruno V Sinn1, John Hackmann19, Marion Kiechle20, Andreas Schneeweiss21, Wilko Weichert3, Carsten Denkert22, Sibylle Loibl23. 1. Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany. 2. German Breast Group (GBG Forschungs GmbH), Neu-Isenburg, Germany. 3. Institute of General and Surgical Pathology of the Technical University of Munich, Technische Universität München, Munich, Germany. 4. Munich Cancer Registry (MCR), Bavarian Cancer Registry - Regional Centre Munich (LGL) at the University Hospital of Munich, Institute of Medical Information Processing, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University (LMU), Munich, Germany. 5. Breast Cancer Center, HELIOS Klinikum, Berlin, Germany. 6. St. Barbara Klinik, Hamm-Heessen, Germany. 7. Mittelbaden Hospital, Karlsruhe, Germany. 8. Department of Gynecology, University of Erlangen-Nürnberg, Erlangen, Germany. 9. Institute of Pathology, Düren, Germany. 10. Department of Gynecology, University Hospital Mannheim, Mannheim, Germany. 11. Institute of Pathology, University of Erlangen-Nürnberg, Erlangen, Germany. 12. Rotkreuzklinikum, Frauenklinik, München, Germany. 13. Department of Gynecology, University of Ulm, Ulm, Germany. 14. Clinic of Obstetrics and Gynaecology, Schleswig-Holstein University Hospital, Kiel, Germany. 15. Oncology Practice at Bethanien Hospital Frankfurt, Frankfurt, Germany. 16. Sana Klinikum Offenbach, Offenbach, Germany. 17. Luisenkrankenhaus, Düsseldorf, Germany. 18. Institute of Pathology, University of Heidelberg, Heidelberg, Germany. 19. Department of Gynecology, Marien Hospital Witten, Witten, Germany. 20. Department of Gynecology and Obstetrics, Comprehensive Cancer Center Munich (CCCM), Klinikum Rechts der Isar, Technical University Munich (TUM), Munich, Germany. 21. Nationales Centrum für Tumorerkrankungen, Universität Heidelberg, Heidelberg, Germany. 22. Institute of Pathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; Institute of Pathology, Philipps-University Marburg and University Hospital Marburg (UKGM), Marburg, Germany. 23. German Breast Group (GBG Forschungs GmbH), Neu-Isenburg, Germany. Electronic address: Sibylle.Loibl@gbg.de.
Abstract
AIM: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. METHODS: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1-9%) and strong-positive (ER or PR 10-100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). RESULTS: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87-1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78-1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23-0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33-0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33-0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). CONCLUSION: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.
AIM: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. METHODS: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1-9%) and strong-positive (ER or PR 10-100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). RESULTS: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87-1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78-1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23-0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33-0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33-0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). CONCLUSION: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.
Keywords:
Breast cancer; Breast neoplasms; Cancer biomarkers; ER-negative PR-negative HER2-negative breast cancer; Hormone-dependent neoplasms; Mammary cancer; Neoadjuvant therapy; Oestrogen receptors; Progesterone receptors; Triple-negative breast cancer
Authors: Nina Ditsch; Achim Wöcke; Michael Untch; Christian Jackisch; Ute-Susann Albert; Maggie Banys-Paluchowski; Ingo Bauerfeind; Jens-Uwe Blohmer; Wilfried Budach; Peter Dall; Eva Maria Fallenberg; Peter A Fasching; Tanja N Fehm; Michael Friedrich; Bernd Gerber; Oleg Gluz; Nadia Harbeck; Jörg Heil; Jens Huober; Hans H Kreipe; David Krug; Thorsten Kühn; Sherko Kümmel; Cornelia Kolberg-Liedtke; Sibylle Loibl; Diana Lüftner; Michael Patrick Lux; Nicolai Maass; Christoph Mundhenke; Ulrike Nitz; Tjoung-Won Park-Simon; Toralf Reimer; Kerstin Rhiem; Achim Rody; Marcus Schmidt; Andreas Schneeweiss; Florian Schütz; Hans-Peter Sinn; Christine Solbach; Erich-Franz Solomayer; Elmar Stickeler; Christoph Thomssen; Isabell Witzel; Volkmar Müller; Wolfgang Janni; Marc Thill Journal: Breast Care (Basel) Date: 2022-05-05 Impact factor: 2.268
Authors: Paolo Tarantino; Chiara Corti; Peter Schmid; Javier Cortes; Elizabeth A Mittendorf; Hope Rugo; Sara M Tolaney; Giampaolo Bianchini; Fabrice Andrè; Giuseppe Curigliano Journal: NPJ Breast Cancer Date: 2022-02-18