Identification of a three-gene expression signature of poor-prognosis breast carcinoma.
BACKGROUND
The clinical course of breast cancer is difficult to predict on the basis of established clinical and pathological prognostic criteria. Given the genetic complexity of breast carcinomas, it is not surprising that correlations with individual genetic abnormalities have also been disappointing. The use of gene expression profiles could result in more accurate and objective prognostication.


RESULTS
To this end, we used real-time quantitative RT-PCR assays to quantify the mRNA expression of a large panel (n = 47) of genes previously identified as candidate prognostic molecular markers in a series of 100 ERalpha-positive breast tumor samples from patients with known long-term follow-up. We identified a three-gene expression signature (BRCA2, DNMT3B and CCNE1) as an independent prognostic marker (P = 0.007 by univariate analysis; P = 0.006 by multivariate analysis). This "poor prognosis" signature was then tested on an independent panel of ERalpha-positive breast tumors from a well-defined cohort of 104 postmenopausal breast cancer patients treated with primary surgery followed by adjuvant tamoxifen alone: although this "poor prognosis" signature was associated with shorter relapse-free survival in univariate analysis (P = 0.029), it did not persist as an independent prognostic factor in multivariate analysis (P = 0.27).


CONCLUSIONS
Our results confirm the value of gene expression signatures in predicting the outcome of breast cancer.
Bièche
Ivan
I
Laboratoire d'Oncogénétique-INSERM E0017, Centre René Huguenin, St-Cloud, France. i.bieche@stcloud-huguenin.org
Tozlu
Sengül
S
Girault
Igor
I
Lidereau
Rosette
R
D000328:Adult; D000368:Aged; D024682:BRCA2 Protein / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D002277:Carcinoma / Q000737:chemistry / Q000175:diagnosis* / Q000628:therapy; D019927:Cyclin E; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D017698:Postmenopause; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D024682:BRCA2 Protein; C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004248:DNA (Cytosine-5-)-Methyltransferases