Jacek Glajzer1,2,3, Dan Cacsire Castillo-Tong4, Rolf Richter5, Ignace Vergote6,7, Hagen Kulbe5,6, Adriaan Vanderstichele6,7, Ilary Ruscito5,6,8, Fabian Trillsch9, Alexander Mustea10, Caroline Kreuzinger4,11, Charlie Gourley12, Hani Gabra13, Eliane T Taube14, Oliver Dorigo15, David Horst14, Carlotta Keunecke5,6, Joanna Baum5,6, Timothy Angelotti16, Jalid Sehouli5,6, Elena Ioana Braicu17,18,19. 1. Department of Gynecology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, Berlin, Germany. jacek.glajzer@uk-erlangen.de. 2. Tumorbank Ovarian Cancer Network, Berlin, Germany. jacek.glajzer@uk-erlangen.de. 3. Department of Oral and Cranio-Maxillofacial Surgery, University Hospital Erlangen, Glückstraße 11, Erlangen, Germany. jacek.glajzer@uk-erlangen.de. 4. Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria. 5. Department of Gynecology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, Berlin, Germany. 6. Tumorbank Ovarian Cancer Network, Berlin, Germany. 7. Division of Gynecological Oncology, Department of Gynaecology and Obstetrics, Leuven Cancer Institute, Universitaire Ziekenhuizen Leuven, Katholieke Universiteit Leuven, Herestraat 49, Leuven, Belgium. 8. Gynecology Division, Department of Medical and Surgical Sciences and Translational Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, Via di Grottarossa 1035, Rome, Italy. 9. Department of Obstetrics and Gynecology, University Hospital LMU Munich, Munich, Germany. 10. Department of Gynecology and Gynecological Oncology, University Hospital Bonn, Venusberg-Campus 1, Bonn, Germany. 11. Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg, Austria. 12. Nicola Murray Centre for Ovarian Cancer Research, University of Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Cancer,, Western General Hospital, Crewe Road South, Edinburgh, UK. 13. Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK. 14. Institute of Pathology, Charité-Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany. 15. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA. 16. Department of Anesthesiology, Perioperative and Pain Medicine, 300 Pasteur Drive H3580, Stanford, CA, USA. 17. Department of Gynecology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Augustenburger Platz 1, Berlin, Germany. elena.braicu@charite.de. 18. Tumorbank Ovarian Cancer Network, Berlin, Germany. elena.braicu@charite.de. 19. Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA, USA. elena.braicu@charite.de.
Abstract
BACKGROUND: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). PATIENTS AND METHODS: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. RESULTS: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. CONCLUSIONS: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.
BACKGROUND: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC). PATIENTS AND METHODS: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups. RESULTS: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence. CONCLUSIONS: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.