Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen
Prat, A. (Universitat Autònoma de Barcelona. Departament de Medicina)
Parker, J. S. (University of North Carolina. Lineberger Comprehensive Cancer Center)
Fan, C. (LUniversity of North Carolina. Lineberger Comprehensive Cancer Center)
Cheang, M. C. U. (University of North Carolina. Lineberger Comprehensive Cancer Center)
Miller, L. D. (Wake Forest School of Medicine. Department of Cancer Biology)
Bergh, Jonas (Manchester University. Department of Medical Oncology)
Chia, S. K. L. (British Columbia Cancer Agency)
Bernard, P. S. (University of Utah Health Sciences Center. Department of Pathology)
Nielsen, T. O. (University of British Columbia. Department of Pathology)
Ellis, Matthew J (Siteman Cancer Center at Washington University. Department of Medicine)
Carey, L. A. (University of North Carolina. Deparment of Medicine)
Perou, Charles M. (University of North Carolina. Pathology & Laboratory Medicine)

Date:	2012
Abstract:	ER-positive (ER+) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only. Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan-Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance. All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8. 5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%-100%). Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
Note:	Funding: NCI Breast SPORE program (P50-CA58223-09A1); (RO1-420 CA138255) Breast Cancer Research Foundation, the Sociedad Española de Oncología Médica (SEOM) and the V Foundation for Cancer Research. AP is affiliated to the Medicine PhD program of the Autonomous University of Barcelona, Spain.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Breast cancer ; Genomics ; Luminal ; Mammaprint ; Oncotype ; PAM50
Published in:	Annals of oncology, Vol. 23 Núm. 11 (november 2012) , p. 2866-2873, ISSN 1569-8041

DOI: 10.1093/annonc/mds080
PMID: 22532584

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