Sophie C J Bosma1, Marlous Hoogstraat2, Erik van Werkhoven3, Michiel de Maaker4, Femke van der Leij5, Paula H M Elkhuizen5, Alain Fourquet6, Philip Poortmans7, Liesbeth J Boersma8, Harry Bartelink5, Marc J van de Vijver9. 1. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: s.bosma@nki.nl. 2. Department of Bioinformatics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Statistics, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 4. Department of Molecular Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 5. Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 6. Department of Radiation Oncology, Institute Curie, Paris, France. 7. Department of Radiation Oncology, Institute Curie, Paris, France; Department of Radiation Oncology, Iridium Netwerk, Wilrijk Antwerp, Belgium; University of Antwerp, Edegem Antwerp, Belgium. 8. Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre, The Netherlands. 9. Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands.
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 ≤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.
PURPOSE: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancerpatients 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.