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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
Contributed by David Botstein, July 17, 2001
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.
Medical Sciences
Gene expression patterns of breast carcinomas distinguish tumor
subclasses with clinical implications
a
T.S. and C.M.P. contributed equally to this work.
www.pnas.org/cgi/doi/10.1073/pnas.191367098
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