100IN - Gene expression profiling of breast cancer: Past and future

Date 01 October 2012
Event ESMO Congress 2012
Session ESMO-ASCO Joint symposium: Genomics in breast cancer: Opening new doors
Topics Breast Cancer
Personalised Medicine
Translational Research
Presenter Christos Sotiriou
Authors C. Sotiriou1, D. Fumagalli2
  • 1Bctl - Breast Cancer Translational Research Laboratory, Institute Jules Bordet, 1000 - Brussels/BE
  • 2Institute Jules Bordet, 1000 - Brussels/BE

Abstract

It is intuitive that a high-throughput technology able to define the expression level of thousands of genes at once is more suited to investigate the complexity of cancer compared to the evaluation of single genes' expression. This explains why the advent of microarray technology has had a profound impact on the way the nature and the clinical evolution of breast cancer (BC) are now perceived and investigated. Several studies have demonstrated that BC consists of different diseases with specific molecular profiles and clinical behaviors that can help selecting patients for enrollment in clinical trials and orienting therapeutic approaches. Microarrays have also been used to identify gene expression signatures (GS) with a prognostic and/or predictive value. After a wave of “first generation signatures” mostly based on the ability of proliferation to discriminate which patients can be spared aggressive treatments, signatures of “second generation” have explored the prognostic value of gene related to immune response and stromal compartment. Multigene classifiers have also been developed to predict response to either generic or specific endocrino- or chemotherapies. Despite the reliability of microarray technology has been demonstrated, the clinical implementation of GS is still limited mostly in relation to the uncertainty of their added value compared to standard clinical-pathological factors. While the results of two big randomized trials will help establishing the clinical role of these GS, the evolution of molecular technologies is setting the stage for a new interpreter. Next generation sequencing technologies are in fact providing an incredible amount of data that is revealing new insight in the complexity of BC nature and evolution. When compared to microarrays, the ability of RNA sequencing to quantify the level of expression of genes seems to be highly correlated for both single genes and gene signatures. Moreover, RNA sequencing has the advantage of identifying additional molecular events such as editing, which can have a major impact on cancer evolution. Even if more data are needed to set the role of this technology, RNA sequencing holds the potential to complement and increase the knowledge acquired so far with microarrays.

Disclosure

All authors have declared no conflicts of interest.