Gene expression predictors of breast cancer outcomes.
BACKGROUND
Correlation of risk factors with genomic data promises to provide specific treatment for individual patients, and needs interpretation of complex, multivariate patterns in gene expression data, as well as assessment of their ability to improve clinical predictions. We aimed to predict nodal metastatic states and relapse for breast cancer patients.


METHODS
We analysed DNA microarray data from samples of primary breast tumours, using non-linear statistical analyses to assess multiple patterns of interactions of groups of genes that have predictive value for the individual patient, with respect to lymph node metastasis and cancer recurrence.


RESULTS
We identified aggregate patterns of gene expression (metagenes) that associate with lymph node status and recurrence, and that are capable of predicting outcomes in individual patients with about 90% accuracy. The metagenes defined distinct groups of genes, suggesting different biological processes underlying these two characteristics of breast cancer. Initial external validation came from similarly accurate predictions of nodal status of a small sample in a distinct population.


CONCLUSIONS
Multiple aggregate measures of profiles of gene expression define valuable predictive associations with lymph node metastasis and disease recurrence for individual patients. Gene expression data have the potential to aid accurate, individualised, prognosis. Importantly, these data are assessed in terms of precise numerical predictions, with ranges of probabilities of outcome. Precise and statistically valid assessments of risks specific for patients, will ultimately be of most value to clinicians faced with treatment decisions.
Huang
Erich
E
Koo Foundation Sun Yat-Sen Cancer Centre, Taipei, Taiwan.
Cheng
Skye H
SH
Dressman
Holly
H
Pittman
Jennifer
J
Tsou
Mei Hua
MH
Horng
Cheng Fang
CF
Bild
Andrea
A
Iversen
Edwin S
ES
Liao
Ming
M
Chen
Chii Ming
CM
West
Mike
M
Nevins
Joseph R
JR
Huang
Andrew T
AT
D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors