Search for a gene-expression signature of breast cancer local recurrence in young women
Menée sur une cohorte initiale de jeunes patientes néerlandaises (148), puis sur une cohorte de patientes françaises (195) atteintes d'un cancer du sein, cette étude évalue les performances d'une signature d'expression de gènes dans la prédiction d'une récidive locale après un traitement conservateur du sein
Purpose: A gene-expression (GE) signature, predictive for local recurrence (LR) after breast-conserving treatment (BCT) has previously been identified from a series of 165 young breast cancer (BC) patients. We evaluated this signature on both another platform and an independent series, compared its performance with other published gene-sets and investigated the GE profile of a larger dataset. Experimental Design: GE tumor profiles were obtained on 148 of the initial 165 Dutch patients and on an independent validation series of 195 French patients. Both unsupervised and supervised classifications were used to study the GE profile of the 343 BCs, and to identify subgroups that differ for their risk of LR. Results: The previous LR signature was validated across platforms. However, when applied to the French patients, the signature did not reproduce its reported performance and did not better classify the patients than other published gene-sets. Hierarchical clustering of all 343 BCs did not show any grouping reflecting LR status. Genes related to proliferation were found differentially expressed between patients with or without LR only in triple-negative tumors. Supervised classification revealed no significant gene-set predictive for LR or able to outperform classification based on clinical variables. Conclusions: Although the previously identified LR signature was robust on another platform, we were neither able to validate it on an independent dataset, nor to define a strong GE classifier for LR using a larger dataset. We conclude that there are no significant differences in GE pattern in tumors from patients with and without LR after BCT.
Clinical Cancer Research , résumé, 2012