Repeated observation of breast tumor subtypes in independent gene expression data sets.
Characteristic patterns of gene expression measured by DNA microarrays have been used to classify tumors into clinically relevant subgroups. In this study, we have refined the previously defined subtypes of breast tumors that could be distinguished by their distinct patterns of gene expression. A total of 115 malignant breast tumors were analyzed by hierarchical clustering based on patterns of expression of 534 "intrinsic" genes and shown to subdivide into one basal-like, one ERBB2-overexpressing, two luminal-like, and one normal breast tissue-like subgroup. The genes used for classification were selected based on their similar expression levels between pairs of consecutive samples taken from the same tumor separated by 15 weeks of neoadjuvant treatment. Similar cluster analyses of two published, independent data sets representing different patient cohorts from different laboratories, uncovered some of the same breast cancer subtypes. In the one data set that included information on time to development of distant metastasis, subtypes were associated with significant differences in this clinical feature. By including a group of tumors from BRCA1 carriers in the analysis, we found that this genotype predisposes to the basal tumor subtype. Our results strongly support the idea that many of these breast tumor subtypes represent biologically distinct disease entities.
Sorlie
Therese
T
Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Tibshirani
Robert
R
Parker
Joel
J
Hastie
Trevor
T
Marron
J S
JS
Nobel
Andrew
A
Deng
Shibing
S
Johnsen
Hilde
H
Pesich
Robert
R
Geisler
Stephanie
S
Demeter
Janos
J
Perou
Charles M
CM
Lønning
Per E
PE
Brown
Patrick O
PO
Børresen-Dale
Anne-Lise
AL
Botstein
David
D
D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000401:mortality; D002277:Carcinoma / Q000737:chemistry / Q000145:classification* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D018734:Genes, erbB-2; D005838:Genotype; D006801:Humans; D015993:Life Tables; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016019:Survival Analysis
D009363:Neoplasm Proteins