Abstract
BackgroundGene expression profiling may improve prognostic accuracy in patients with early breast cancer. Our objective was to demonstrate that it is possible to develop a simple molecular signature to predict distant relapse.MethodsWe included 153 patients with stage I-II hormonal receptor-positive breast cancer. RNA was isolated from formalin-fixed paraffin-embedded samples and qRT-PCR amplification of 83 genes was performed with gene expression assays. The genes we analyzed were those included in the 70-Gene Signature, the Recurrence Score and the Two-Gene Index. The association among gene expression, clinical variables and distant metastasis-free survival was analyzed using Cox regression models.ResultsAn 8-gene prognostic score was defined. Distant metastasis-free survival at 5 years was 97% for patients defined as low-risk by the prognostic score versus 60% for patients defined as high-risk. The 8-gene score remained a significant factor in multivariate analysis and its performance was similar to that of two validated gene profiles: the 70-Gene Signature and the Recurrence Score. The validity of the signature was verified in independent cohorts obtained from the GEO database.ConclusionsThis study identifies a simple gene expression score that complements histopathological prognostic factors in breast cancer, and can be determined in paraffin-embedded samples.
Highlights
Gene expression profiling may improve prognostic accuracy in patients with early breast cancer
A key aspect of the management of women with early breast cancer is the selection of adjuvant therapy, which is guided by the use of prognostic factors included in the guidelines[1,2]
We have previously demonstrated that 1) quantitative reversetranscriptase polymerase chain reaction can be used to assess the genes included in the 70-Gene Signature and 2) commercially available probes can be used on formalin-fixed, paraffin-embedded (FFPE) samples to determine the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio [5,6]
Summary
Gene expression profiling may improve prognostic accuracy in patients with early breast cancer. A key aspect of the management of women with early breast cancer is the selection of adjuvant therapy, which is guided by the use of prognostic factors included in the guidelines[1,2]. Gene expression profiles may improve prognostic and predictive information in breast cancer patients, so that adjuvant chemotherapy is given only to those with the higher risk. The major drawbacks to the widespread use of gene expression profiling include reservations regarding their cost/effectiveness ratio and their lack of widespread availability. We have previously demonstrated that 1) quantitative reversetranscriptase polymerase chain reaction (qRT-PCR) can be used to assess the genes included in the 70-Gene Signature and 2) commercially available probes can be used on formalin-fixed, paraffin-embedded (FFPE) samples to determine the 70-Gene Signature, the Recurrence Score and the Two-Gene Ratio [5,6]
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