학술논문

A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial
Document Type
article
Source
Oncotarget. 7(31)
Subject
Breast Cancer
Genetics
Cancer
Clinical Research
Clinical Trials and Supportive Activities
Detection
screening and diagnosis
4.2 Evaluation of markers and technologies
Adult
Aged
Anthracyclines
Antibiotics
Antineoplastic
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Biomarkers
Tumor
Breast Neoplasms
Chemotherapy
Adjuvant
Chromosomal Instability
Cyclophosphamide
Disease-Free Survival
Epirubicin
Female
Fluorouracil
Gene Expression Profiling
Humans
Middle Aged
Paclitaxel
Prognosis
Taxoids
breast cancer
chromosome instability
predictive biomarker
anthracycline
taxane
Oncology and Carcinogenesis
Language
Abstract
Recent evidence demonstrated CIN4 as a predictive marker of anthracycline benefit in early breast cancer. An analysis of the NCIC CTG MA.21 clinical trial was performed to test the role of existing CIN gene expression signatures as prognostic and predictive markers in the context of taxane based chemotherapy.RNA was extracted from patients in cyclophosphamide, epirubicin and flurouracil (CEF) and epirubicin, cyclophosphamide and paclitaxel (EC/T) arms of the NCIC CTG MA.21 trial and analysed using NanoString technology.After multivariate analysis both high CIN25 and CIN70 score was significantly associated with an increased in RFS (HR 1.76, 95%CI 1.07-2.86, p=0.0018 and HR 1.59, 95%CI 1.12-2.25, p=0.0096 respectively). Patients whose tumours had low CIN4 gene expression scores were associated with an increase in RFS (HR: 0.64, 95% CI 0.39-1.03, p=0.06) when treated with EC/T compared to patients treated with CEF.In conclusion we have demonstrated CIN25 and CIN70 as prognostic markers in breast cancer and that CIN4 is a potential predictive maker of benefit from taxane treatment.