Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG

TY - JOUR

T1 - Clinical and molecular characterization of BRCA-associated breast cancer

T2 - results from the DBCG

AU - Soenderstrup, I. M.H.

AU - Laenkholm, A. V.

AU - Jensen, M. B.

AU - Eriksen, J. O.

AU - Gerdes, A. M.

AU - Hansen, T. V.O.

AU - Kruse, T. A.

AU - Larsen, M. J.

AU - Pedersen, I. S.

AU - Rossing, M.

AU - Thomassen, M.

AU - Ejlertsen, B.

PY - 2018/1/2

Y1 - 2018/1/2

N2 - 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.

AB - 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.

U2 - 10.1080/0284186x.2017.1398415

DO - 10.1080/0284186x.2017.1398415

M3 - Journal article

C2 - 29164974

AN - SCOPUS:85034639743

SN - 0284-186X

VL - 57

SP - 95

EP - 101

JO - Acta Oncologica

JF - Acta Oncologica

IS - 1

ER -