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

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftActa Oncologica
Vol/bind57
Udgave nummer1
Sider (fra-til)95-101
ISSN0284-186X
DOI
StatusUdgivet - jan. 2018
Begivenhed16th Acta Oncologica Symposium - Aarhus , Danmark
Varighed: 18. jan. 201819. jan. 2018

Konference

Konference16th Acta Oncologica Symposium
LandDanmark
ByAarhus
Periode18/01/201819/01/2018

Fingeraftryk

Disease-Free Survival
Neoplasms
Mutation
Proportional Hazards Models
Paraffin
Registries
Multivariate Analysis
Databases
Pathology

Citer dette

Soenderstrup, I. M. H., Laenkholm, A. V., Jensen, M. B., Eriksen, J. O., Gerdes, A. M., Hansen, T. V. O., ... 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
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. / Clinical and molecular characterization of BRCA-associated breast cancer : results from the DBCG. I: Acta Oncologica. 2018 ; Bind 57, Nr. 1. s. 95-101.
@inproceedings{0e7667927a124a468a808d13175727ea,
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.",
keywords = "Adolescent, Adult, Aged, BRCA1 Protein/genetics, BRCA2 Protein/genetics, Breast Neoplasms/genetics, Chemotherapy, Adjuvant, Denmark/epidemiology, Disease-Free Survival, Female, Genetic Predisposition to Disease, Heterozygote, Humans, Mastectomy, Middle Aged, Mutation, Neoplasm Recurrence, Local/genetics, Registries, Young Adult",
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 = "1",
doi = "10.1080/0284186X.2017.1398415",
language = "English",
volume = "57",
pages = "95--101",
journal = "Acta Oncologica",
issn = "0284-186X",
publisher = "Taylor & Francis",
number = "1",

}

Soenderstrup, IMH, Laenkholm, AV, Jensen, MB, Eriksen, JO, Gerdes, AM, Hansen, TVO, Kruse, TA, Larsen, MJ, Pedersen, IS, Rossing, M, Thomassen, M & Ejlertsen, B 2018, 'Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG', Acta Oncologica, bind 57, nr. 1, s. 95-101. https://doi.org/10.1080/0284186X.2017.1398415

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

I: Acta Oncologica, Bind 57, Nr. 1, 01.2018, s. 95-101.

Publikation: Bidrag til tidsskriftKonferenceartikelForskningpeer review

TY - GEN

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

Y1 - 2018/1

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.

KW - Adolescent

KW - Adult

KW - Aged

KW - BRCA1 Protein/genetics

KW - BRCA2 Protein/genetics

KW - Breast Neoplasms/genetics

KW - Chemotherapy, Adjuvant

KW - Denmark/epidemiology

KW - Disease-Free Survival

KW - Female

KW - Genetic Predisposition to Disease

KW - Heterozygote

KW - Humans

KW - Mastectomy

KW - Middle Aged

KW - Mutation

KW - Neoplasm Recurrence, Local/genetics

KW - Registries

KW - Young Adult

U2 - 10.1080/0284186X.2017.1398415

DO - 10.1080/0284186X.2017.1398415

M3 - Conference article

VL - 57

SP - 95

EP - 101

JO - Acta Oncologica

JF - Acta Oncologica

SN - 0284-186X

IS - 1

ER -

Soenderstrup IMH, Laenkholm AV, Jensen MB, Eriksen JO, Gerdes AM, Hansen TVO et al. Clinical and molecular characterization of BRCA-associated breast cancer: results from the DBCG. Acta Oncologica. 2018 jan;57(1):95-101. https://doi.org/10.1080/0284186X.2017.1398415