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Clinical Cancer Research Vol. 12, 5705-5712, October 1, 2006
© 2006 American Association for Cancer Research


Imaging, Diagnosis, Prognosis

Gene Expression Profiles of Primary Breast Carcinomas from Patients at High Risk for Local Recurrence after Breast-Conserving Therapy

Bas Kreike1,3, Hans Halfwerk2,3, Petra Kristel2,3, Annuska Glas2, Hans Peterse2, Harry Bartelink1 and Marc J. van de Vijver2

Authors' Affiliations: Departments of 1 Radiation Oncology, 2 Diagnostic Oncology, and 3 Experimental Therapy, the Netherlands Cancer Institute, Amsterdam, the Netherlands

Requests for reprints: Marc J. van de Vijver, Department of Diagnostic Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Phone: 31-20-512-2750; Fax: 31-20-512-2759; E-mail: m.vd.vijver{at}nki.nl.

Purpose: Several risk factors for local recurrence of breast cancer after breast-conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also in improving understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence.

Experimental Design: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients, 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9 of 19 patients, the local recurrence was also available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences.

Results: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences.

Conclusions: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after BCT were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy.




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Copyright © 2006 by the American Association for Cancer Research.