An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

M. A. Vollebergh; E. H. Lips; P. M. Nederlof; L. F. A. Wessels; M. K. Schmidt; E. H. van Beers; S. Cornelissen; M. Holtkamp; F. E. Froklage; E. G. E. de Vries; J. G. Schrama; J. Wesseling; M. J. van de Vijver; H. van Tinteren; M. de Bruin; M. Hauptmann; S. Rodenhuis; S. C. Linn

doi:10.1093/annonc/mdq624

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

M. A. Vollebergh, E. H. Lips, P. M. Nederlof, L. F. A. Wessels, M. K. Schmidt, E. H. van Beers, S. Cornelissen, M. Holtkamp, F. E. Froklage, E. G. E. de Vries, J. G. Schrama, J. Wesseling, M. J. van de Vijver, H. van Tinteren, M. de Bruin, M. Hauptmann, S. Rodenhuis, S. C. Linn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

154 Citations (Scopus)

Abstract

Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).

Results: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).

Conclusion: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.

Original language	English
Pages (from-to)	1561-1570
Number of pages	10
Journal	Annals of Oncology
Volume	22
Issue number	7
DOIs	https://doi.org/10.1093/annonc/mdq624
Publication status	Published - Jul-2011

Keywords

array comparative genomic hybridisation
BRCA1
breast cancer
high-dose chemotherapy
platinum salt
predictive marker
COMPARATIVE GENOMIC HYBRIDIZATION
PHASE-II
ESTROGEN-RECEPTOR
MUTATION CARRIERS
BRCA1 MUTATIONS
GENE-EXPRESSION
OVARIAN-TUMORS
CYCLOPHOSPHAMIDE
CARCINOMAS
TRIAL

Access to Document

10.1093/annonc/mdq624

Handle.net

Persistent link

Cite this

Vollebergh, M. A., Lips, E. H., Nederlof, P. M., Wessels, L. F. A., Schmidt, M. K., van Beers, E. H., Cornelissen, S., Holtkamp, M., Froklage, F. E., de Vries, E. G. E., Schrama, J. G., Wesseling, J., van de Vijver, M. J., van Tinteren, H., de Bruin, M., Hauptmann, M., Rodenhuis, S., & Linn, S. C. (2011). An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients. Annals of Oncology, 22(7), 1561-1570. https://doi.org/10.1093/annonc/mdq624

@article{fb3ad2ec10f44024a06ed821714971b5,

title = "An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients",

abstract = "Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).Results: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18\%, multivariate hazard ratio (HR) = 0.12, 95\% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82\%, HR = 0.78, 95\% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).Conclusion: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.",

keywords = "array comparative genomic hybridisation, BRCA1, breast cancer, high-dose chemotherapy, platinum salt, predictive marker, COMPARATIVE GENOMIC HYBRIDIZATION, PHASE-II, ESTROGEN-RECEPTOR, MUTATION CARRIERS, BRCA1 MUTATIONS, GENE-EXPRESSION, OVARIAN-TUMORS, CYCLOPHOSPHAMIDE, CARCINOMAS, TRIAL",

author = "Vollebergh, \{M. A.\} and Lips, \{E. H.\} and Nederlof, \{P. M.\} and Wessels, \{L. F. A.\} and Schmidt, \{M. K.\} and \{van Beers\}, \{E. H.\} and S. Cornelissen and M. Holtkamp and Froklage, \{F. E.\} and \{de Vries\}, \{E. G. E.\} and Schrama, \{J. G.\} and J. Wesseling and \{van de Vijver\}, \{M. J.\} and \{van Tinteren\}, H. and \{de Bruin\}, M. and M. Hauptmann and S. Rodenhuis and Linn, \{S. C.\}",

year = "2011",

month = jul,

doi = "10.1093/annonc/mdq624",

language = "English",

volume = "22",

pages = "1561--1570",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "7",

}

Vollebergh, MA, Lips, EH, Nederlof, PM, Wessels, LFA, Schmidt, MK, van Beers, EH, Cornelissen, S, Holtkamp, M, Froklage, FE, de Vries, EGE, Schrama, JG, Wesseling, J, van de Vijver, MJ, van Tinteren, H, de Bruin, M, Hauptmann, M, Rodenhuis, S & Linn, SC 2011, 'An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients', Annals of Oncology, vol. 22, no. 7, pp. 1561-1570. https://doi.org/10.1093/annonc/mdq624

TY - JOUR

T1 - An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

AU - Vollebergh, M. A.

AU - Lips, E. H.

AU - Nederlof, P. M.

AU - Wessels, L. F. A.

AU - Schmidt, M. K.

AU - van Beers, E. H.

AU - Cornelissen, S.

AU - Holtkamp, M.

AU - Froklage, F. E.

AU - de Vries, E. G. E.

AU - Schrama, J. G.

AU - Wesseling, J.

AU - van de Vijver, M. J.

AU - van Tinteren, H.

AU - de Bruin, M.

AU - Hauptmann, M.

AU - Rodenhuis, S.

AU - Linn, S. C.

PY - 2011/7

Y1 - 2011/7

N2 - Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).Results: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).Conclusion: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.

AB - Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss through mutation or promoter methylation and immunohistochemical basal-like status in the triple-negative subgroup (TN subgroup).Results: We observed greater benefit from HD-PB chemotherapy versus conventional chemotherapy among patients with BRCA1-like(CGH) tumours [41/230 = 18%, multivariate hazard ratio (HR) = 0.12, 95% confidence interval (CI) 0.04-0.43] compared with patients with non-BRCA1-like(CGH) tumours (189/230 = 82%, HR = 0.78, 95% CI 0.50-1.20), with a significant difference (test for interaction P = 0.006). Similar results were obtained for overall survival (P interaction = 0.04) and when analyses were restricted to the TN subgroup. Sixty-three percent (20/32) of assessable BRCA1-like(CGH) tumours harboured either a BRCA1 mutation (n = 8) or BRCA1 methylation (n = 12).Conclusion: BRCA1 loss as assessed by CGH analysis can identify patients with substantially improved outcome after adjuvant DSB-inducing chemotherapy when compared with standard anthracycline-based chemotherapy in our series.

KW - array comparative genomic hybridisation

KW - BRCA1

KW - breast cancer

KW - high-dose chemotherapy

KW - platinum salt

KW - predictive marker

KW - COMPARATIVE GENOMIC HYBRIDIZATION

KW - PHASE-II

KW - ESTROGEN-RECEPTOR

KW - MUTATION CARRIERS

KW - BRCA1 MUTATIONS

KW - GENE-EXPRESSION

KW - OVARIAN-TUMORS

KW - CYCLOPHOSPHAMIDE

KW - CARCINOMAS

KW - TRIAL

U2 - 10.1093/annonc/mdq624

DO - 10.1093/annonc/mdq624

M3 - Article

SN - 0923-7534

VL - 22

SP - 1561

EP - 1570

JO - Annals of Oncology

JF - Annals of Oncology

IS - 7

ER -

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this