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Cancer Res DOI:10.1158/0008-5472.CAN-07-0539

High expression of lymphocyte-associated genes in node-negative HER2+ breast cancers correlates with lower recurrence rates.

Publication TypeJournal Article
Year of Publication2007
AuthorsAlexe, G, Dalgin, GS, Scanfeld, D, Tamayo, P, Mesirov, JP, DeLisi, C, Harris, L, Barnard, N, Martel, M, Levine, AJ, Ganesan, S, Bhanot, G
JournalCancer Res
Date Published2007 Nov 15
KeywordsBreast Neoplasms, Cell Proliferation, Cluster Analysis, Computational Biology, Databases, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Lymphocytes, Multigene Family, Neoplasm Invasiveness, Principal Component Analysis, Receptor, ErbB-2, Recurrence, RNA, Messenger

Gene expression analysis has identified biologically relevant subclasses of breast cancer. However, most classification schemes do not robustly cluster all HER2+ breast cancers, in part due to limitations and bias of clustering techniques used. In this article, we propose an alternative approach that first separates the HER2+ tumors using a gene amplification signal for Her2/neu amplicon genes and then applies consensus ensemble clustering separately to the HER2+ and HER2- clusters to look for further substructure. We applied this procedure to a microarray data set of 286 early-stage breast cancers treated only with surgery and radiation and identified two basal and four luminal subtypes in the HER2- tumors, as well as two novel and robust HER2+ subtypes. HER2+ subtypes had median distant metastasis-free survival of 99 months [95% confidence interval (95% CI), 83-118 months] and 33 months (95% CI, 11-54 months), respectively, and recurrence rates of 11% and 58%, respectively. The low recurrence subtype had a strong relative overexpression of lymphocyte-associated genes and was also associated with a prominent lymphocytic infiltration on histologic analysis. These data suggest that early-stage HER2+ cancers associated with lymphocytic infiltration are a biologically distinct subtype with an improved natural history.


Alternate JournalCancer Res.
PubMed ID18006808