Andreas D Hartkopf1, Sara Y Brucker2, Florin-Andrei Taran3, Nadia Harbeck4, Alexandra von Au5, Bjørn Naume6, Jean-Yves Pierga7, Oliver Hoffmann8, Matthias W Beckmann9, Lisa Rydén10, Tanja Fehm11, Rebecca Aft12, Montserrat Solà13, Vincent Walter2, Brigitte Rack14, Florian Schuetz5, Elin Borgen15, Minh-Hanh Ta16, Ann-Kathrin Bittner8, Peter A Fasching9, Mårten Fernö17, Natalia Krawczyk11, Katherine Weilbaecher12, Mireia Margelí18, Markus Hahn2, Julia Jueckstock4, Christoph Domschke5, Francois-Clement Bidard7, Sabine Kasimir-Bauer8, Birgitt Schoenfisch2, Ayse G Kurt4, Markus Wallwiener5, Gerhard Gebauer19, Christoph A Klein20, Diethelm Wallwiener2, Wolfgang Janni14, Klaus Pantel21. 1. Department of Women's Health, University of Tuebingen, Tuebingen, Germany. Electronic address: andreas.hartkopf@med.uni-tuebingen.de. 2. Department of Women's Health, University of Tuebingen, Tuebingen, Germany. 3. Department of Women's Health, University of Tuebingen, Tuebingen, Germany; Department of Obstetrics and Gynecology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany. 4. Breast Center, Department of Obstetrics and Gynecology, University of Munich (LMU), Munich, Germany. 5. Department of Gynecology and Obstetrics, Heidelberg University Hospital, National Center for Tumor Diseases (NCT) Heidelberg, Germany. 6. Department of Oncology, Oslo University Hospital and Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 7. Department of Medical Oncology, Institut Curie, Paris and Saint Cloud, France. 8. Department of Gynecology and Obstetrics, University Hospital of Essen, Essen, Germany. 9. Department of Gynecology and Obstetrics, Comprehensive Cancer Center Erlangen-EMN, Erlangen University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Germany. 10. Department of Clinical Sciences Lund, Division of Oncology-Pathology and Surgery, Lund University, Lund, Sweden. 11. Department of Gynecology and Obstetrics, Duesseldorf University Hospital, Duesseldorf, Germany. 12. Washington University, St. Louis, MO, USA. 13. Department of Nuclear Medicine, Hospital Germans Trias I Pujol, Badalona, Spain. 14. Department of Gynecology and Obstetrics, Ulm University Hospital, Ulm, Germany. 15. Department of Pathology, Oslo University Hospital, Oslo, Norway. 16. Department of Medical Oncology, Institut Curie, Paris and Saint Cloud, France; University of Medicine Paris Descartes, Paris, France. 17. Department of Clinical Sciences Lund, Oncology-Pathology, Lund University, Lund, Sweden. 18. ICO-Badalona, Medical Oncology Service, B-ARGO, Badalona, Spain. 19. Department of Gynecology and Obstetrics, Asklepios Klinik Barmbek, Nord-Heidberg and Wandsbek, Hamburg, Germany. 20. Experimental Medicine and Therapy Research, University of Regensburg, Regensburg, Germany. 21. Department of Tumor Biology, Center of Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Abstract
PURPOSE: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. EXPERIMENTAL DESIGN: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. RESULTS: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512). CONCLUSIONS: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
PURPOSE: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. EXPERIMENTAL DESIGN: Individual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. RESULTS: In total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06-1.43, p = 0.006), 1.30 (95% CI: 1.12-1.52, p < 0.001) and 1.30 (95% CI: 1.08-1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68-2.16; p = 0.512). CONCLUSIONS: DTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.
Authors: Léa Volmer; André Koch; Sabine Matovina; Dominik Dannehl; Martin Weiss; Ganna Welker; Markus Hahn; Tobias Engler; Markus Wallwiener; Christina Barbara Walter; Ernst Oberlechner; Sara Yvonne Brucker; Klaus Pantel; Andreas Hartkopf Journal: Cancers (Basel) Date: 2022-01-27 Impact factor: 6.639