Journal Article

Practical implications of gene-expression-based assays for breast oncologists

Ellis, Matthew J., Prat, Aleix, Perou, Charles M.

2012

Overview

Gene-expression profiling has led to the development of signatures designed to predict survival and treatment response in patients with breast cancer. In this Review, Prat et al . discuss the clinical utility of gene-expression-based assays and compare them with the performance of breast cancer biomarkers that are currently used as standard of care. Gene-expression profiling has had a considerable impact on our understanding of breast cancer biology, and more recently on clinical care. Two statistical approaches underlie these advancements. Supervised analyses have led to the development of gene-expression signatures designed to predict survival and/or treatment response, which has resulted in the development of new clinical assays. Unsupervised analyses have identified numerous biological signatures including signatures of cell type of origin, signaling pathways, and of cellular proliferation. Included within these biological signatures are the molecular subtypes known as the 'intrinsic' subtypes of breast cancer. This classification has expanded our appreciation of the heterogeneity of breast cancer and has provided a way to sub-classify the disease in a manner that might have clinical utility. In this Review, we discuss the clinical utility of gene-expression-based assays and their technical potential as clinical tools vis-a-vis the performance of breast cancer biomarkers that are the current standard of care. Key Points Gene-expression-based assays provide independent prognostic information beyond standard clinical-pathological variables; however, tumor and nodal stage remain important and must be taken into account in the final prognostic assessment Gene-expression-based assays identify patients with ER-positive node-negative disease at low risk of relapse after treatment with hormonal therapy and who might be spared from chemotherapy Clinical use of gene-expression-based assays for the prediction of chemotherapy benefit in node-positive disease, and in ER-negative disease, is currently experimental Current methodologies for ER, PR and HER2 testing might benefit from additional protocol standardizations, but may still be less reproducible than standardized gene-expression-based assays Non-standardized research-based identification of the intrinsic subtypes shows concordance values equivalent to current clinical testing for histological grade, ER, PR and HER2 For daily clinical use, we recommend the highest level of reproducibility/concordance (Level 1), which will only be achieved for pathology and gene-expression-based tests by using a single platform and standardized protocol

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/1647/2217/2018 / 692/699/67/1347 / 692/699/67/1857 / 692/700/139 / Biological assay / Biomarkers, Tumor / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - mortality / Care and treatment / Diagnosis / Female / Gene expression / Gene Expression Profiling - methods / Genes, erbB-2 - genetics / Health Status Indicators / Humans / Medical Oncology - methods / Medical Oncology - statistics & numerical data / Medicine / Medicine & Public Health / Methods / Microarray Analysis / Oncology / Receptors, Estrogen / Receptors, Progesterone / review-article / United States