Jenny Furlanetto1, Volker Möbus2, Andreas Schneeweiss3, Kerstin Rhiem4, Hans Tesch5, Jens-Uwe Blohmer6, Kristina Lübbe7, Michael Untch8, Christoph Salat9, Jens Huober10, Peter Klare11, Rita Schmutzler4, Fergus J Couch12, Bianca Lederer13, Bernd Gerber14, Dirk-Michael Zahm15, Ingo Bauerfeind16, Valentina Nekljudova13, Claus Hanusch17, Christian Jackisch18, Theresa Link19, Eric Hahnen4, Sibylle Loibl13, Peter A Fasching20. 1. German Breast Group, Neu-Isenburg, Germany. Electronic address: Jenny.Furlanetto@gbg.de. 2. Medical Clinic II, University Hospital Frankfurt, Germany. 3. National Center for Tumour Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany. 4. Center for Familial Breast and Ovarian Cancer, University Clinic Köln, Germany. 5. Center for Hematology and Oncology Bethanien Frankfurt, Germany. 6. Breast Center Charité-University Medicine Berlin, Germany. 7. DIAKOVERE Henriettenstift, Clinic for Gynaecological Surgery, Senology and Oncology, Hannover, Germany. 8. HELIOS Clinic Berlin Buch, Germany. 9. Hematological-oncological Practice Salat/Stötzer, München, Germany. 10. University Women's Hospital Ulm, Germany. 11. MediOnko-Institute GbR Berlin, Germany. 12. Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. 13. German Breast Group, Neu-Isenburg, Germany. 14. University Women's Hospital at Clinic Südstadt, Rostock. 15. SRH Wald-Clinic Gera, Germany. 16. Clinic Landshut, Germany. 17. Red Cross Hospital München, Germany. 18. Sana-Clinic, Offenbach, Germany. 19. Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany. 20. Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
Abstract
BACKGROUND: BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities. METHODS: Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored. RESULTS: Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p < 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies. CONCLUSIONS: gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research.
BACKGROUND:BRCA1 and BRCA2 play a central role in DNA repair. Therefore, patients harbouring germline (g) BRCA1/2 mutations (m) treated with chemotherapy might be at higher risk of haematological toxicities. METHODS:Patients from German Breast Group (GBG) and Arbeitsgemeinschaft Gynäkologische Onkologie-breast group studies with early triple-negative breast cancer (TNBC) and known gBRCA1/2m status treated with anthracycline-taxane-based neoadjuvant chemotherapy were analysed. Primary objective was the rate of neutropenia grade (G)III-IV in cycle 1 (C1). Secondary objectives included effects on overall and other haematological toxicities GIII-IV in C1, cumulative haematological toxicity across all cycles, relative total dose intensity, and granulocyte-colony stimulating factor prophylaxis. Haematological toxicities under taxanes, carboplatin, and cyclophosphamide were explored. RESULTS: Two hundred nine of 1171 (17.8%) evaluated patients had gBRCA1/2m. In C1, 37.4% gBRCA1/2m versus 35.7% wild-type patients had neutropenia GIII-IV (P = 0.683). For C1, gBRCA1/2m predicted neither for neutropenia GIII-IV (odds ratio [OR]: 1.26, 95% confidence intervals [CI]: 0.87-1.82, P = 0.226) nor for other haematological toxicities GIII-IV (OR: 0.91, 95% CI: 0.64-1.31, P = 0.625) in multivariable regression models. Analyses of cumulative toxicities across all cycles yielded similar results except thrombocytopaenia GIII-IV, which was increased in gBRCA1m patients. In patients treated with taxanes, the rate of haematological toxicities GIII-IV was higher in gBRCA1/2m compared with wild-type (59.5% versus 43.1%; p < 0.001). No difference was seen under cyclophosphamide or platinum-containing chemotherapies. CONCLUSIONS: gBRCA1/2m was not associated with higher risk of overall severe haematological toxicities in the first cycle or cumulatively across all cycles under standard chemotherapy for TNBC. Under taxane, patients with gBRCA1/2m might have a higher risk of haematological toxicities GIII-IV, requiring further research.