Search for a gene expression signature of breast cancer local recurrence in young women

Nicolas Servant, Marc A Bollet, Hans Halfwerk, Kevin Bleakley, Bas Kreike, Laurent Jacob, Daoud Sie, Ron M Kerkhoven, Philippe Hupé, Rim Hadhri, Alain Fourquet, Harry Bartelink, Emmanuel Barillot, Brigitte Sigal-Zafrani, Marc J van de Vijver

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

PURPOSE: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.

EXPERIMENTAL DESIGN: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.

RESULTS: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.

CONCLUSIONS: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.

Original languageEnglish
Pages (from-to)1704-15
Number of pages12
JournalClinical Cancer Research
Volume18
Issue number6
DOIs
Publication statusPublished - 15 Mar 2012

Cite this

Servant, N., Bollet, M. A., Halfwerk, H., Bleakley, K., Kreike, B., Jacob, L., ... van de Vijver, M. J. (2012). Search for a gene expression signature of breast cancer local recurrence in young women. Clinical Cancer Research, 18(6), 1704-15. https://doi.org/10.1158/1078-0432.CCR-11-1954
Servant, Nicolas ; Bollet, Marc A ; Halfwerk, Hans ; Bleakley, Kevin ; Kreike, Bas ; Jacob, Laurent ; Sie, Daoud ; Kerkhoven, Ron M ; Hupé, Philippe ; Hadhri, Rim ; Fourquet, Alain ; Bartelink, Harry ; Barillot, Emmanuel ; Sigal-Zafrani, Brigitte ; van de Vijver, Marc J. / Search for a gene expression signature of breast cancer local recurrence in young women. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 6. pp. 1704-15.
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title = "Search for a gene expression signature of breast cancer local recurrence in young women",
abstract = "PURPOSE: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.EXPERIMENTAL DESIGN: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.RESULTS: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.CONCLUSIONS: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.",
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author = "Nicolas Servant and Bollet, {Marc A} and Hans Halfwerk and Kevin Bleakley and Bas Kreike and Laurent Jacob and Daoud Sie and Kerkhoven, {Ron M} and Philippe Hup{\'e} and Rim Hadhri and Alain Fourquet and Harry Bartelink and Emmanuel Barillot and Brigitte Sigal-Zafrani and {van de Vijver}, {Marc J}",
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Servant, N, Bollet, MA, Halfwerk, H, Bleakley, K, Kreike, B, Jacob, L, Sie, D, Kerkhoven, RM, Hupé, P, Hadhri, R, Fourquet, A, Bartelink, H, Barillot, E, Sigal-Zafrani, B & van de Vijver, MJ 2012, 'Search for a gene expression signature of breast cancer local recurrence in young women' Clinical Cancer Research, vol. 18, no. 6, pp. 1704-15. https://doi.org/10.1158/1078-0432.CCR-11-1954

Search for a gene expression signature of breast cancer local recurrence in young women. / Servant, Nicolas; Bollet, Marc A; Halfwerk, Hans; Bleakley, Kevin; Kreike, Bas; Jacob, Laurent; Sie, Daoud; Kerkhoven, Ron M; Hupé, Philippe; Hadhri, Rim; Fourquet, Alain; Bartelink, Harry; Barillot, Emmanuel; Sigal-Zafrani, Brigitte; van de Vijver, Marc J.

In: Clinical Cancer Research, Vol. 18, No. 6, 15.03.2012, p. 1704-15.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Search for a gene expression signature of breast cancer local recurrence in young women

AU - Servant, Nicolas

AU - Bollet, Marc A

AU - Halfwerk, Hans

AU - Bleakley, Kevin

AU - Kreike, Bas

AU - Jacob, Laurent

AU - Sie, Daoud

AU - Kerkhoven, Ron M

AU - Hupé, Philippe

AU - Hadhri, Rim

AU - Fourquet, Alain

AU - Bartelink, Harry

AU - Barillot, Emmanuel

AU - Sigal-Zafrani, Brigitte

AU - van de Vijver, Marc J

PY - 2012/3/15

Y1 - 2012/3/15

N2 - PURPOSE: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.EXPERIMENTAL DESIGN: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.RESULTS: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.CONCLUSIONS: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.

AB - PURPOSE: A gene expression signature, predictive for local recurrence after breast-conserving treatment, has previously been identified from a series of 165 young patients with breast cancer. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets, and investigated the gene expression profile of a larger data set.EXPERIMENTAL DESIGN: Gene expression tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the gene expression profile of the 343 breast cancers and to identify subgroups that differ for their risk of local recurrence.RESULTS: The previous local recurrence signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene sets. Hierarchical clustering of all 343 breast cancers did not show any grouping reflecting local recurrence status. Genes related to proliferation were found differentially expressed between patients with or without local recurrence only in triple-negative tumors. Supervised classification revealed no significant gene set predictive for local recurrence or able to outperform classification based on clinical variables.CONCLUSIONS: Although the previously identified local recurrence signature was robust on another platform, we were neither able to validate it on an independent data set, nor able to define a strong gene expression classifier for local recurrence using a larger data set. We conclude that there are no significant differences in gene expression pattern in tumors from patients with and without local recurrence after breast-conserving treatment.

KW - Adult

KW - Breast Neoplasms/genetics

KW - Female

KW - Gene Expression Profiling

KW - Humans

KW - Prognosis

KW - Recurrence

KW - Validation Studies as Topic

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DO - 10.1158/1078-0432.CCR-11-1954

M3 - Article

VL - 18

SP - 1704

EP - 1715

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

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