High Expression of Lymphocyte-Associated Genes in Node-Negative HER2+ Breast Cancers Correlates with Lower Recurrence Rates

Cancer Res. 2007;67(22):10669-76.. Published: 2007.11.14

Gabriela Alexe, Gul S. Dalgin, Daniel Scanfeld, Pablo Tamayo, Jill P. Mesirov, Charles DeLisi, Lyndsay Harris, Nicola Barnard, Maritza Martel, Arnold J. Levine, Shridar Ganesan and Gyan Bhanot

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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.


Supplemental Data

Description Link/Filename
Supplementary Appendix 1 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/1
Supplementary Figure A4-1 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/2
Supplementary Figure A6-1 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/3
Supplementary Figure A6-2 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/4
Supplementary Figure A2-1 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/5
Supplementary Table 1 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/6
Supplementary Table 2 http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/7
Supplementary Table 3a http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/8
Supplementary Table 3b http://cancerres.aacrjournals.org/cgi/data/67/22/10669/DC1/9