Joanna Tomiczek-Szwiec1, Marek Szwiec2,3, Michal Falco4, Cezary Cybulski5, Dominika Wokolorczyk5, Anna Jakubowska5, Jacek Gronwald5, Malgorzata Stawicka6, Dariusz Godlewski7, Ewa Kilar8, Elzbieta Marczyk9, Monika Siołek10, Rafal Wiśniowski11, Olga Haus12, Robert Sibilski2,13, Lubomir Bodnar14, Ping Sun15, Steven A Narod16, Jan Lubinski5, Tomasz Huzarski5,6. 1. Department of Histology, Department of Biology and Genetics, Faculty of Medicine, University of Opole, Opole, Poland. 2. Department of Surgery and Oncology, University of Zielona Góra, Zyty 28 St, 65-046, Zielona Góra, Poland. 3. Department of Clinical Oncology, University Hospital in Zielona Góra, Zyty 26 St, 65-046, Zielona Góra, Poland. 4. Regional Oncology Hospital, Strzalowska 22, 71-730, Szczecin, Poland. 5. Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Unii Lubelskiej 1 St, 71-252, Szczecin, Poland. 6. Department of Clinical Genetics and Pathology, University of Zielona Góra, Zyty 28 St, 65-046, Zielona Góra, Poland. 7. OPEN, Kazimierza Wielkiego 24 St, 61-863, Poznań, Poland. 8. Department of Oncology, District Specialist Hospital, Leśna 27-29 St, 58-100, Świdnica, Poland. 9. Department of Oncological Surgery, Regional Oncology Center, Gancarska 11 St, 31-115, Kraków, Poland. 10. Holycross Cancer Center, Artwińskiego 3 St, 25-734, Kielce, Poland. 11. Regional Oncology Hospital, Wyzwolenia 18 St, 43-300, Bielsko Biała, Poland. 12. Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, Jagiellońska 13 St, 85-067, Bydgoszcz, Poland. 13. Oncology Diagnostic Center, Wazów 42 St, 65-044, Zielona Góra, Poland. 14. Department of Oncology and Immuno-oncology, School of Medicine, Collegium Medicum, Uniwersity of Warmia and Mazury in Olsztyn, Warszawska 30 St, 10-082, Olsztyn, Poland. 15. Women's College Research Institute, Toronto, Ontario, M5S 1B2, Canada. 16. Women's College Research Institute, Toronto, Ontario, M5S 1B2, Canada. steven.narod@wchospital.ca.
Abstract
BACKGROUND: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation. METHODS: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast cancer or for benign conditions. Dates of death were obtained from the Polish Vital Statistics Registry. Causes of death were determined by medical record review. Predictors of survival were determined using the Cox proportional hazards model. RESULTS: In all, 839 patients with a CHEK2 mutation were matched to 839 patients without a mutation. The mean follow-up was 12.0 years. The 15-year survival for CHEK2 carriers was 76.6% and the 15-year survival for non-carrier control patients was 78.8% (adjusted HR = 1.06; 95% CI: 0.84-1.34; P = 0.61). Among CHEK2 carriers, the 15-year survival for women who had an oophorectomy was 86.3% and for women who did not have an oophorectomy was 72.1% (adjusted HR = 0.59; 95% CI: 0.38-0.90; P = 0.02). Among controls, the 15-year survival for patients who had an oophorectomy was 84.5% and for women who did not have an oophorectomy was 77.6% (adjusted HR = 1.03; 95% CI: 0.66-1.61; P = 0.90). CONCLUSION: Among women with breast cancer and a CHEK2 mutation, oophorectomy is associated with a reduced risk of death from breast cancer.
BACKGROUND: To estimate the impact of oophorectomy and other treatments on the survival of breast cancer patients with a CHEK2 mutation. METHODS: Women with Stage I-III breast cancer who were treated at 17 hospitals in Poland were tested for four founder mutations in the CHEK2 gene. 974 women (10%) were positive for a CHEK2 mutation. Control patients without a CHEK2 mutation were selected from a database of patients treated over the same time period. Information on treatments received and distant recurrences were retrieved from medical records. Treatments included chemotherapy, hormonal therapy (tamoxifen) and radiation therapy. Oophorectomies were performed for the treatment of breast cancer or for benign conditions. Dates of death were obtained from the Polish Vital Statistics Registry. Causes of death were determined by medical record review. Predictors of survival were determined using the Cox proportional hazards model. RESULTS: In all, 839 patients with a CHEK2 mutation were matched to 839 patients without a mutation. The mean follow-up was 12.0 years. The 15-year survival for CHEK2 carriers was 76.6% and the 15-year survival for non-carrier control patients was 78.8% (adjusted HR = 1.06; 95% CI: 0.84-1.34; P = 0.61). Among CHEK2 carriers, the 15-year survival for women who had an oophorectomy was 86.3% and for women who did not have an oophorectomy was 72.1% (adjusted HR = 0.59; 95% CI: 0.38-0.90; P = 0.02). Among controls, the 15-year survival for patients who had an oophorectomy was 84.5% and for women who did not have an oophorectomy was 77.6% (adjusted HR = 1.03; 95% CI: 0.66-1.61; P = 0.90). CONCLUSION: Among women with breast cancer and a CHEK2 mutation, oophorectomy is associated with a reduced risk of death from breast cancer.
Authors: Stephanie L Greville-Heygate; Tom Maishman; William J Tapper; Ramsey I Cutress; Ellen Copson; Alison M Dunning; Linda Haywood; Louise J Jones; Diana M Eccles Journal: JCO Precis Oncol Date: 2020-05-04