Thérese Sørlie1, Charles M. Perou1, Robert Tibshirani1, Turid Aas1, Stephanie Geisler1, Hilde Johnsen1, Trevor Hastie1, Michael B. Eisen1, Matt van de Rijn1, Stefanie S. Jeffrey1, David E. Gloriam1, H. Quist1, John C. Matese1, Patrick O. Brown1, David Botstein1, Per Eystein Lønning1, Arto Mannermaa1
1Departments of Genetics and Surgery, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway; Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599; Departments of Health Research and Policy and Statistics, Genetics, Pathology, Surgery, and Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Departments of Medicine (Section of Oncology), Surgery, and Biochemical...
Tóm tắt
The purpose of this study was to classify breast carcinomas based on variations in gene expression patterns derived from cDNA microarrays and to correlate tumor characteristics to clinical outcome. A total of 85 cDNA microarray experiments representing 78 cancers, three fibroadenomas, and four normal breast tissues were analyzed by hierarchical clustering. As reported previously, the cancers could be classified into a basal epithelial-like group, an
ERBB2
-overexpressing group and a normal breast-like group based on variations in gene expression. A novel finding was that the previously characterized luminal epithelial/estrogen receptor-positive group could be divided into at least two subgroups, each with a distinctive expression profile. These subtypes proved to be reasonably robust by clustering using two different gene sets: first, a set of 456 cDNA clones previously selected to reflect intrinsic properties of the tumors and, second, a gene set that highly correlated with patient outcome. Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
