Therese Sørlie ^{a, b, c}, Charles M. Perou ^{a, d}, Robert Tibshirani ^e, Turid Aas ^f, Stephanie Geisler ^g, Hilde Johnsen ^b, Trevor Hastie ^e, Michael B. Eisen ^h, Matt van de Rijn ⁱ, Stefanie S. Jeffrey ^j, Thor Thorsen ^k, Hanne Quist ^l, John C. Matese ^c, Patrick O. Brown ^m, David Botstein ^c, Per Eystein Lønning ^g, and Anne-Lise Børresen-Dale ^{b, n}

Departments of  ^b Genetics and ^l Surgery, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway;
^d Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599;
Departments of  ^e Health Research and Policy and Statistics, ^c Genetics, ⁱ Pathology, ^j Surgery, and ^m Biochemistry and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305;
Departments of  ^g Medicine (Section of Oncology), ^f Surgery, and ^k Biochemical Endocrinology, Haukeland University Hospital, N-5021 Bergen, Norway; and
^h Life Sciences Division, Lawrence Orlando Berkeley National Laboratories, and Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720

^a T.S. and C.M.P. contributed equally to this work.

ⁿ To whom reprint requests should be addressed. E-mail:  alb@labmed.uio.no

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. 

1. Frenster JH, and Herstein PR, "Gene De-repression", New Eng. J. Med. 288: 1224-1229 (June 7, 1973).