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

I. M.H. Soenderstrup; A. V. Laenkholm; M. B. Jensen; J. O. Eriksen; A. M. Gerdes; T. V.O. Hansen; T. A. Kruse; M. J. Larsen; I. S. Pedersen; M. Rossing; M. Thomassen; B. Ejlertsen

doi:10.1080/0284186x.2017.1398415

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

I. M.H. Soenderstrup^*, A. V. Laenkholm, M. B. Jensen, J. O. Eriksen, A. M. Gerdes, T. V.O. Hansen, T. A. Kruse, M. J. Larsen, I. S. Pedersen, M. Rossing, M. Thomassen, B. Ejlertsen

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

9 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Acta Oncologica
Vol/bind	57
Udgave nummer	1
Sider (fra-til)	95-101
ISSN	0284-186X
DOI	https://doi.org/10.1080/0284186x.2017.1398415
Status	Udgivet - 2 jan. 2018

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10.1080/0284186x.2017.1398415

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Soenderstrup, I. M. H., Laenkholm, A. V., Jensen, M. B., Eriksen, J. O., Gerdes, A. M., Hansen, T. V. O., Kruse, T. A., Larsen, M. J., Pedersen, I. S., Rossing, M., Thomassen, M., & Ejlertsen, B. (2018). Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG. Acta Oncologica, 57(1), 95-101. https://doi.org/10.1080/0284186x.2017.1398415

@article{2dbc29e84f574230a304eac449021337,

title = "Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG",

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.",

author = "Soenderstrup, {I. M.H.} and Laenkholm, {A. V.} and Jensen, {M. B.} and Eriksen, {J. O.} and Gerdes, {A. M.} and Hansen, {T. V.O.} and Kruse, {T. A.} and Larsen, {M. J.} and Pedersen, {I. S.} and M. Rossing and M. Thomassen and B. Ejlertsen",

year = "2018",

month = jan,

day = "2",

doi = "10.1080/0284186x.2017.1398415",

language = "English",

volume = "57",

pages = "95--101",

journal = "Acta Oncologica, Supplement",

issn = "1100-1704",

publisher = "Taylor & Francis",

number = "1",

}

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 - 1100-1704

VL - 57

SP - 95

EP - 101

JO - Acta Oncologica, Supplement

JF - Acta Oncologica, Supplement

IS - 1

ER -

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

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