A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

Sophie C. J. Bosma; Marlous Hoogstraat; Erik van Werkhoven; Michiel de Maaker; Femke van der Leij; Paula H. M. Elkhuizen; Alain Fourquet; Philip Poortmans; Liesbeth J. Boersma; Harry Bartelink; Marc J. van de Vijver; Young Boost Trial research group

doi:10.1016/j.radonc.2020.11.025

A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

Sophie C. J. Bosma^*, Marlous Hoogstraat, Erik van Werkhoven, Michiel de Maaker, Femke van der Leij, Paula H. M. Elkhuizen, Alain Fourquet, Philip Poortmans, Liesbeth J. Boersma, Harry Bartelink, Marc J. van de Vijver, Young Boost Trial research group

^*Corresponding author for this work

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

Abstract

Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the "Young Boost Trial".

Material & methods: In the "Young Boost Trial" 2421 patients

Results: The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81-3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR.

Conclusions: All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified. (C) 2020 Elsevier B.V. All rights reserved.

Original language	English
Pages (from-to)	127-135
Number of pages	9
Journal	Radiotherapy and Oncology
Volume	156
DOIs	https://doi.org/10.1016/j.radonc.2020.11.025
Publication status	Published - Mar 2021

Keywords

Early-stage breast cancer
Breast conserving therapy
Local control

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10.1016/j.radonc.2020.11.025

1 Erratum / corrigendum / retractions

Corrigendum to "A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients" [Radiother Oncol 156 (2021) 127-135]
Bosma, S. C. J., Hoogstraat, M., van Werkhoven, E., de Maaker, M., van der Leij, F., Elkhuizen, P. H. M., Fourquet, A., Poortmans, P., Boersma, L. J., Bartelink, H., van de Vijver, M. J. & Young Boost Trial research group, Oct 2021, In: Radiotherapy and Oncology. 163, p. 244-244 1 p.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

Cite this

Bosma, S. C. J., Hoogstraat, M., van Werkhoven, E., de Maaker, M., van der Leij, F., Elkhuizen, P. H. M., Fourquet, A., Poortmans, P., Boersma, L. J., Bartelink, H., van de Vijver, M. J., & Young Boost Trial research group (2021). A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients. Radiotherapy and Oncology, 156, 127-135. https://doi.org/10.1016/j.radonc.2020.11.025

@article{ec0286a3308c4745b608c699cce3b08e,

title = "A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients",

abstract = "Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the {"}Young Boost Trial{"}.Material & methods: In the {"}Young Boost Trial{"} 2421 patientsResults: The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81-3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR.Conclusions: All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified. (C) 2020 Elsevier B.V. All rights reserved.",

keywords = "Early-stage breast cancer, Breast conserving therapy, Local control",

author = "Bosma, {Sophie C. J.} and Marlous Hoogstraat and {van Werkhoven}, Erik and {de Maaker}, Michiel and {van der Leij}, Femke and Elkhuizen, {Paula H. M.} and Alain Fourquet and Philip Poortmans and Boersma, {Liesbeth J.} and Harry Bartelink and {van de Vijver}, {Marc J.} and {Young Boost Trial research group}",

note = "Funding Information: The data management of the YBT was supported by a grant of the Dutch Cancer Society (CKTO 2003-13). The analysis of cosmetic outcome in this paper was supported by a Pink Ribbon grant (2011.WO04.C94). The French part of the trial was funded by the French Ministry of Health PHRC2009 and PHRC2012 grants. Also, we acknowledge and thank Alain Fourquet, project leader in France, for coordinating the Young Boost Trial in France and the following investigators for their active participation: M. van Hezewijk, Leiden (NL); M.J.C. van der Sangen Eindhoven (NL); M.C. Stenfert Kroese, Deventer (NL); J.J.Jobsen, Enschede (NL); J.M. Immink, Delft (NL); M.E. Mast, Den Haag (NL); F.M. Gescher, Den Haag (NL); N. Bijker, Amsterdam (NL); J.W.M. Mens, Rotterdam (NL); W.G.J.M. Smit, Leeuwarden (NL); D.H.F. Rietveld, {\'e}Amsterdam (NL); I. Lecouillard, Rennes (Fr); C Breton-Callu, Bordeaux (Fr); H. Marsiglia, Villejuif (Fr); J. Thariat, Nice (Fr); A. Benyoucef, Rouen (Fr); A. Labib, Saint Cloud (Fr); M. Aumont, Saint Herblain (Fr); P. Bontemps, Besancon (Fr); C. Le Foll, Lagny (Fr); Y. Belkacemi, Cr{\'e}teil (Fr); O. Chapet, Lyon (Fr); V. Strnad, Erlangen (De). We would like to acknowledge the NKI-AVL genomics core facility, in particular Marielle Kret{\'e} for RNA library prep, Janneke Kruizinga for the DNA library prep, Wim Brugman for performing next generation sequencing, Iris de Rink and Roel Kluin for primary data analysis and Marja Nieuwland and Ron Kerkhoven for technical guidance and supervision. We would like to acknowledge the NKI-AVL Core facility Molecular pathology & biobanking (CFMPB) for laboratorsupport. We would like to acknowledge and thank Jelle Wesseling and Esther Lips for general supervision of the molecular pathology research group. Funding Information: The data management of the YBT was supported by a grant of the Dutch Cancer Society ( CKTO 2003-13 ). The analysis of cosmetic outcome in this paper was supported by a Pink Ribbon grant ( 2011.WO04.C94 ). The French part of the trial was funded by the French Ministry of Health PHRC2009 and PHRC2012 grants. Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2021",

month = mar,

doi = "10.1016/j.radonc.2020.11.025",

language = "English",

volume = "156",

pages = "127--135",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

}

Bosma, SCJ, Hoogstraat, M, van Werkhoven, E, de Maaker, M, van der Leij, F, Elkhuizen, PHM, Fourquet, A, Poortmans, P, Boersma, LJ, Bartelink, H, van de Vijver, MJ & Young Boost Trial research group 2021, 'A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients', Radiotherapy and Oncology, vol. 156, pp. 127-135. https://doi.org/10.1016/j.radonc.2020.11.025

TY - JOUR

T1 - A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

AU - Bosma, Sophie C. J.

AU - Hoogstraat, Marlous

AU - van Werkhoven, Erik

AU - de Maaker, Michiel

AU - van der Leij, Femke

AU - Elkhuizen, Paula H. M.

AU - Fourquet, Alain

AU - Poortmans, Philip

AU - Boersma, Liesbeth J.

AU - Bartelink, Harry

AU - van de Vijver, Marc J.

AU - Young Boost Trial research group

N1 - Funding Information: The data management of the YBT was supported by a grant of the Dutch Cancer Society (CKTO 2003-13). The analysis of cosmetic outcome in this paper was supported by a Pink Ribbon grant (2011.WO04.C94). The French part of the trial was funded by the French Ministry of Health PHRC2009 and PHRC2012 grants. Also, we acknowledge and thank Alain Fourquet, project leader in France, for coordinating the Young Boost Trial in France and the following investigators for their active participation: M. van Hezewijk, Leiden (NL); M.J.C. van der Sangen Eindhoven (NL); M.C. Stenfert Kroese, Deventer (NL); J.J.Jobsen, Enschede (NL); J.M. Immink, Delft (NL); M.E. Mast, Den Haag (NL); F.M. Gescher, Den Haag (NL); N. Bijker, Amsterdam (NL); J.W.M. Mens, Rotterdam (NL); W.G.J.M. Smit, Leeuwarden (NL); D.H.F. Rietveld, éAmsterdam (NL); I. Lecouillard, Rennes (Fr); C Breton-Callu, Bordeaux (Fr); H. Marsiglia, Villejuif (Fr); J. Thariat, Nice (Fr); A. Benyoucef, Rouen (Fr); A. Labib, Saint Cloud (Fr); M. Aumont, Saint Herblain (Fr); P. Bontemps, Besancon (Fr); C. Le Foll, Lagny (Fr); Y. Belkacemi, Créteil (Fr); O. Chapet, Lyon (Fr); V. Strnad, Erlangen (De). We would like to acknowledge the NKI-AVL genomics core facility, in particular Marielle Kreté for RNA library prep, Janneke Kruizinga for the DNA library prep, Wim Brugman for performing next generation sequencing, Iris de Rink and Roel Kluin for primary data analysis and Marja Nieuwland and Ron Kerkhoven for technical guidance and supervision. We would like to acknowledge the NKI-AVL Core facility Molecular pathology & biobanking (CFMPB) for laboratorsupport. We would like to acknowledge and thank Jelle Wesseling and Esther Lips for general supervision of the molecular pathology research group. Funding Information: The data management of the YBT was supported by a grant of the Dutch Cancer Society ( CKTO 2003-13 ). The analysis of cosmetic outcome in this paper was supported by a Pink Ribbon grant ( 2011.WO04.C94 ). The French part of the trial was funded by the French Ministry of Health PHRC2009 and PHRC2012 grants. Publisher Copyright: © 2020 Elsevier B.V.

PY - 2021/3

Y1 - 2021/3

N2 - Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the "Young Boost Trial".Material & methods: In the "Young Boost Trial" 2421 patientsResults: The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81-3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR.Conclusions: All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified. (C) 2020 Elsevier B.V. All rights reserved.

AB - Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the "Young Boost Trial".Material & methods: In the "Young Boost Trial" 2421 patientsResults: The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81-3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR.Conclusions: All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified. (C) 2020 Elsevier B.V. All rights reserved.

KW - Early-stage breast cancer

KW - Breast conserving therapy

KW - Local control

U2 - 10.1016/j.radonc.2020.11.025

DO - 10.1016/j.radonc.2020.11.025

M3 - Article

C2 - 33245949

SN - 0167-8140

VL - 156

SP - 127

EP - 135

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

ER -

A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients

Abstract

Keywords

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Research output

Corrigendum to "A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients" [Radiother Oncol 156 (2021) 127-135]

Cite this