A gene-expression signature as a predictor of survival in breast cancer.
BACKGROUND
A more accurate means of prognostication in breast cancer will improve the selection of patients for adjuvant systemic therapy.


METHODS
Using microarray analysis to evaluate our previously established 70-gene prognosis profile, we classified a series of 295 consecutive patients with primary breast carcinomas as having a gene-expression signature associated with either a poor prognosis or a good prognosis. All patients had stage I or II breast cancer and were younger than 53 years old; 151 had lymph-node-negative disease, and 144 had lymph-node-positive disease. We evaluated the predictive power of the prognosis profile using univariable and multivariable statistical analyses.


RESULTS
Among the 295 patients, 180 had a poor-prognosis signature and 115 had a good-prognosis signature, and the mean (+/-SE) overall 10-year survival rates were 54.6+/-4.4 percent and 94.5+/-2.6 percent, respectively. At 10 years, the probability of remaining free of distant metastases was 50.6+/-4.5 percent in the group with a poor-prognosis signature and 85.2+/-4.3 percent in the group with a good-prognosis signature. The estimated hazard ratio for distant metastases in the group with a poor-prognosis signature, as compared with the group with the good-prognosis signature, was 5.1 (95 percent confidence interval, 2.9 to 9.0; P<0.001). This ratio remained significant when the groups were analyzed according to lymph-node status. Multivariable Cox regression analysis showed that the prognosis profile was a strong independent factor in predicting disease outcome.


CONCLUSIONS
The gene-expression profile we studied is a more powerful predictor of the outcome of disease in young patients with breast cancer than standard systems based on clinical and histologic criteria.
van de Vijver
Marc J
MJ
Division of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
He
Yudong D
YD
van't Veer
Laura J
LJ
Dai
Hongyue
H
Hart
Augustinus A M
AA
Voskuil
Dorien W
DW
Schreiber
George J
GJ
Peterse
Johannes L
JL
Roberts
Chris
C
Marton
Matthew J
MJ
Parrish
Mark
M
Atsma
Douwe
D
Witteveen
Anke
A
Glas
Annuska
A
Delahaye
Leonie
L
van der Velde
Tony
T
Bartelink
Harry
H
Rodenhuis
Sjoerd
S
Rutgers
Emiel T
ET
Friend
Stephen H
SH
Bernards
René
R
D000328:Adult; D000367:Age Factors; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D018579:Patient Selection; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis