I M H Soenderstrup1, A V Laenkholm1, M B Jensen2, J O Eriksen1, A M Gerdes3, T V O Hansen4, T A Kruse5, M J Larsen5, I S Pedersen6, M Rossing4, M Thomassen5, B Ejlertsen1,7. 1. a Department of Surgical Pathology Region Zealand , Zealand University Hospital , Slagelse , Denmark. 2. b Danish Breast Cancer Group , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark. 3. c Department of Clinical Genetics , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark. 4. d Center for Genomic Medicine , Rigshospitalet Copenhagen University Hospital , Copenhagen , Denmark. 5. e Department of Clinical Genetics , Odense University Hospital , Odense , Denmark. 6. f Section of Molecular Diagnostics , Clinical Biochemistry, Aalborg University Hospital , Aalborg , Denmark. 7. g Department of Oncology , Rigshospitalet, Copenhagen University Hospital , Copenhagen , Denmark.
Abstract
BACKGROUND: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . MATERIAL AND METHODS: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed on paraffin-embedded tumor tissue. Information on risk reducing surgery was obtained from the Danish Pathology and Patient Registries and included as time-dependent variables in Cox proportional hazard models. RESULTS: Ten-year OS and DFS for BRCA1 BC patients were 78% (95% CI 69-85) and 74% (95% CI 64-81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78-94) and 84% (95% CI 74-91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28-6.05, p = .01), but BRCA mutation was not associated with OS (adjusted HR 1.98, 95% CI 0.87-4.52, p = .10). In multivariate analysis, including both BRCA1 and BRCA2 carriers, no chemotherapy was associated with a higher risk of death (adjusted OS HR 3.58, 95% CI 1.29-9.97, p = .01) and risk reducing contralateral mastectomy (RRCM) was associated with a significantly reduced risk of death (adjusted OS HR 0.42, 95% CI =0.21-0.84, p = .01). CONCLUSION: Difference in OS between BRCA1 and BRCA2 BC patients could be ascribed to tumor-biology. BRCA1 BC patients may have a shorter ten-year DFS than BRCA2 BC patients. Chemotherapy and risk reducing contralateral mastectomy reduce mortality for both BRCA1 and BRCA2 BC patients.
BACKGROUND: In breast cancer (BC) patients a cancer predisposing BRCA1/2 mutation is associated with adverse tumor characteristics, risk assessment and treatment allocation. We aimed to estimate overall- (OS) and disease-free survival (DFS) according to tumor characteristics and treatment among women who within two years of definitive surgery for primary BC were shown to carry a mutation in BRCA1/2 . MATERIAL AND METHODS: From the clinical database of the Danish Breast Cancer Group we included 141 BRCA1 and 96 BRCA2 BC patients. Estrogen receptor and HER2 status were centrally reviewed on paraffin-embedded tumor tissue. Information on risk reducing surgery was obtained from the Danish Pathology and Patient Registries and included as time-dependent variables in Cox proportional hazard models. RESULTS: Ten-year OS and DFS for BRCA1 BC patients were 78% (95% CI 69-85) and 74% (95% CI 64-81). Ten-year OS and DFS for BRCA2 BC were 88% (95% CI 78-94) and 84% (95% CI 74-91). BRCA1 BC patients as compared to BRCA2 BC patients had a higher risk of BC relapse or non-breast cancer within ten years of follow-up, independent of ER status (adjusted HR 2.78 95% CI 1.28-6.05, p = .01), but BRCA mutation was not associated with OS (adjusted HR 1.98, 95% CI 0.87-4.52, p = .10). In multivariate analysis, including both BRCA1 and BRCA2 carriers, no chemotherapy was associated with a higher risk of death (adjusted OS HR 3.58, 95% CI 1.29-9.97, p = .01) and risk reducing contralateral mastectomy (RRCM) was associated with a significantly reduced risk of death (adjusted OS HR 0.42, 95% CI =0.21-0.84, p = .01). CONCLUSION: Difference in OS between BRCA1 and BRCA2 BC patients could be ascribed to tumor-biology. BRCA1 BC patients may have a shorter ten-year DFS than BRCA2 BC patients. Chemotherapy and risk reducing contralateral mastectomy reduce mortality for both BRCA1 and BRCA2 BC patients.
Authors: Alan D McCrorie; Susannah Ashfield; Aislinn Begley; Colin Mcilmunn; Patrick J Morrison; Clinton Boyd; Bryony Eccles; Stephanie Greville-Heygate; Ellen R Copson; Ramsey I Cutress; Diana M Eccles; Kienan I Savage; Stuart A McIntosh Journal: J Pathol Clin Res Date: 2020-02-05
Authors: Nanna Jørgensen; Thomas Vauvert F Hviid; Lise B Nielsen; Ida M H Sønderstrup; Jens Ole Eriksen; Bent Ejlertsen; Anne-Marie Gerdes; Torben A Kruse; Mads Thomassen; Maj-Britt Jensen; Anne-Vibeke Lænkholm Journal: Br J Cancer Date: 2021-08-07 Impact factor: 9.075
Authors: Elinborg J Olafsdottir; Ake Borg; Maj-Britt Jensen; Anne-Marie Gerdes; Anna L V Johansson; Rosa B Barkardottir; Oskar T Johannsson; Bent Ejlertsen; Ida Marie Heeholm Sønderstrup; Eivind Hovig; Anne-Vibeke Lænkholm; Thomas van Overeem Hansen; Gudridur H Olafsdottir; Maria Rossing; Jon G Jonasson; Stefan Sigurdsson; Niklas Loman; Martin P Nilsson; Steven A Narod; Laufey Tryggvadottir Journal: Br J Cancer Date: 2020-09-17 Impact factor: 7.640