Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer.
BACKGROUND
Genome-wide measures of gene expression can identify patterns of gene activity that subclassify tumours and might provide a better means than is currently available for individual risk assessment in patients with lymph-node-negative breast cancer.


METHODS
We analysed, with Affymetrix Human U133a GeneChips, the expression of 22000 transcripts from total RNA of frozen tumour samples from 286 lymph-node-negative patients who had not received adjuvant systemic treatment.


RESULTS
In a training set of 115 tumours, we identified a 76-gene signature consisting of 60 genes for patients positive for oestrogen receptors (ER) and 16 genes for ER-negative patients. This signature showed 93% sensitivity and 48% specificity in a subsequent independent testing set of 171 lymph-node-negative patients. The gene profile was highly informative in identifying patients who developed distant metastases within 5 years (hazard ratio 5.67 [95% CI 2.59-12.4]), even when corrected for traditional prognostic factors in multivariate analysis (5.55 [2.46-12.5]). The 76-gene profile also represented a strong prognostic factor for the development of metastasis in the subgroups of 84 premenopausal patients (9.60 [2.28-40.5]), 87 postmenopausal patients (4.04 [1.57-10.4]), and 79 patients with tumours of 10-20 mm (14.1 [3.34-59.2]), a group of patients for whom prediction of prognosis is especially difficult.


CONCLUSIONS
The identified signature provides a powerful tool for identification of patients at high risk of distant recurrence. The ability to identify patients who have a favourable prognosis could, after independent confirmation, allow clinicians to avoid adjuvant systemic therapy or to choose less aggressive therapeutic options.
Wang
Yixin
Y
Veridex LLC, a Johnson & Johnson Company, San Diego, CA, USA.
Klijn
Jan G M
JG
Zhang
Yi
Y
Sieuwerts
Anieta M
AM
Look
Maxime P
MP
Yang
Fei
F
Talantov
Dmitri
D
Timmermans
Mieke
M
Meijer-van Gelder
Marion E
ME
Yu
Jack
J
Jatkoe
Tim
T
Berns
Els M J J
EM
Atkins
David
D
Foekens
John A
JA
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012372:ROC Curve; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012680:Sensitivity and Specificity
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone