Low Concordance between Gene Expression Signatures in ER Positive HER2 Negative Breast Carcinoma Could Impair Their Clinical Application

• Published in: PloS one 2016-02, Vol.11 (2), p.e0148957-e0148957
• Main Authors: Laas, Enora, Mallon, Peter, Duhoux, Francois P, Hamidouche, Amina, Rouzier, Roman, Reyal, Fabien
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Breast; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer genetics; Cancer therapies; Chemotherapy; Clinical medicine; Cluster Analysis; Datasets; Discordance; ErbB-2 protein; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes; Genetic aspects; Genomics; Humans; Kaplan-Meier Estimate; Medical prognosis; Medicine and Health Sciences; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Patients; Physical Sciences; Physiological aspects; Prognosis; Receptor, ErbB-2 - genetics; Receptors, Estrogen - genetics; Reproducibility of Results; Research and Analysis Methods; Risk; Risk factors; Risk groups; Signatures; Standardization; Studies; Surgery; Survival; Transcriptome; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148957

Numerous prognostic gene expression signatures have been recently described. Among the signatures there is variation in the constituent genes that are utilized. We aim to evaluate prognostic concordance among eight gene expression signatures, on a large dataset of ER positive HER2 negative breast cancers. We analysed the performance of eight gene expression signatures on six different datasets of ER+ HER2- breast cancers. Survival analyses were performed using the Kaplan-Meier estimate of survival function. We assessed discrimination and concordance between the 8 signatures on survival and recurrence rates The Nottingham Prognostic Index (NPI) was used to to stratify the risk of recurrence/death. The discrimination ability of the whole signatures, showed fair discrimination performances, with AUC ranging from 0.64 (95%CI 0.55-0.73 for the 76-genes signatures, to 0.72 (95%CI 0.64-0.8) for the Molecular Prognosis Index T17. Low concordance was found in predicting events in the intermediate and high-risk group, as defined by the NPI. Low risk group was the only subgroup with a good signatures concordance. Genomic signatures may be a good option to predict prognosis as most of them perform well at the population level. They exhibit, however, a high degree of discordance in the intermediate and high-risk groups. The major benefit that we could expect from gene expression signatures is the standardization of proliferation assessment.