Discovery and validation of breast cancer subtypes.
BACKGROUND
Previous studies demonstrated breast cancer tumor tissue samples could be classified into different subtypes based upon DNA microarray profiles. The most recent study presented evidence for the existence of five different subtypes: normal breast-like, basal, luminal A, luminal B, and ERBB2+.


RESULTS
Based upon the analysis of 599 microarrays (five separate cDNA microarray datasets) using a novel approach, we present evidence in support of the most consistently identifiable subtypes of breast cancer tumor tissue microarrays being: ESR1+/ERBB2-, ESR1-/ERBB2-, and ERBB2+ (collectively called the ESR1/ERBB2 subtypes). We validate all three subtypes statistically and show the subtype to which a sample belongs is a significant predictor of overall survival and distant-metastasis free probability.


CONCLUSIONS
As a consequence of the statistical validation procedure we have a set of centroids which can be applied to any microarray (indexed by UniGene Cluster ID) to classify it to one of the ESR1/ERBB2 subtypes. Moreover, the method used to define the ESR1/ERBB2 subtypes is not specific to the disease. The method can be used to identify subtypes in any disease for which there are at least two independent microarray datasets of disease samples.
Kapp
Amy V
AV
Department of Statistics, Stanford University, Stanford, CA, USA. AKapp@stanford.edu
Jeffrey
Stefanie S
SS
Langerød
Anita
A
Børresen-Dale
Anne-Lise
AL
Han
Wonshik
W
Noh
Dong-Young
DY
Bukholm
Ida R K
IR
Nicolau
Monica
M
Brown
Patrick O
PO
Tibshirani
Robert
R
D000465:Algorithms; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis