A 38-gene expression signature to predict metastasis risk in node-positive breast cancer after systemic adjuvant chemotherapy: a genomic substudy of PACS01 clinical trial - Archive ouverte HAL Access content directly
Journal Articles Breast Cancer Research and Treatment Year : 2008

A 38-gene expression signature to predict metastasis risk in node-positive breast cancer after systemic adjuvant chemotherapy: a genomic substudy of PACS01 clinical trial

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Mario Campone

Abstract

Currently, no prognostic gene-expression signature (GES) established from node-positive breast cancer cohorts, able to predict evolution after systemic adjuvant chemotherapy, exists. Gene-expression profiles of 252 node-positive breast cancer patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array. In the training cohort, we established a GES composed of 38 genes (38-GES) for the purpose of predicting metastasis-free survival. The 38-GES yielded unadjusted hazard ratio (HR) of 4.86 (95% confidence interval = 2.76–8.56). Even when adjusted with the best two clinicopathological prognostic indexes: Nottingham prognostic index (NPI) and Adjuvant!, 38-GES HRs were 3.30 (1.81–5.99) and 3.40 (1.85–6.24), respectively. Furthermore, 38-GES improved NPI and Adjuvant! classification. In particular, NPI intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 6.97 [2.51–19.36]). Similarly, Adjuvant! intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 4.34 [1.64–11.48]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts ( = 224) generated from different microarray platforms, with HR = 2.95 (1.74–5.01). Moreover, 38-GES showed prognostic performance in supplementary cohorts with different lymph-node status and endpoints (1,040 new patients). The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and is especially powerful to refine NPI and Adjuvant! classification for those patients.
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hal-00478287 , version 1 (30-04-2010)

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Pascal Jézéquel, Mario Campone, Henri H. Roché, Wilfried Gouraud, Catherine Charbonnel, et al.. A 38-gene expression signature to predict metastasis risk in node-positive breast cancer after systemic adjuvant chemotherapy: a genomic substudy of PACS01 clinical trial. Breast Cancer Research and Treatment, 2008, 116 (3), pp.509-520. ⟨10.1007/s10549-008-0250-8⟩. ⟨hal-00478287⟩
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