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 - Young Boost Trial research group
AU - van de Vijver, Marc J.
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, ?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?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? 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 - 2021/3/1
Y1 - 2021/3/1
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 patients ≤50 years old were randomized between a 16 Gy and 26 Gy boost after breast conserving surgery and whole breast radiation (50 Gy). We performed a case-control study comparing patients who developed a LR (cases) and for each of them three control patients free of recurrence (controls). Clinicopathological factors, copy number- and gene expression profiles of primary tumors were compared between cases and controls, and between primary tumors and local recurrences. 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.
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 patients ≤50 years old were randomized between a 16 Gy and 26 Gy boost after breast conserving surgery and whole breast radiation (50 Gy). We performed a case-control study comparing patients who developed a LR (cases) and for each of them three control patients free of recurrence (controls). Clinicopathological factors, copy number- and gene expression profiles of primary tumors were compared between cases and controls, and between primary tumors and local recurrences. 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.
KW - Breast conserving therapy
KW - Early-stage breast cancer
KW - Local control
UR - http://www.scopus.com/inward/record.url?scp=85098721513&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.radonc.2020.11.025
DO - https://doi.org/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 -