A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial
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Melanie Spears1,2, Nicola Lyttle1, Alister D’Costa1,3, Bingshu E. Chen4, Cindy Q. Yao1,3, Paul C. Boutros3,5,6, Margot Burnell7, Mark N. Levine8, Patti O’Brien4, Lois Shepherd4, John M.S. Bartlett1,2,9
1Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada
2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada
3Informatics and Bio-Computing, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada
4NCIC Clinical Trials Group (NCIC CTG) and Queen’s University, Kingston, ON, Canada
5Department of Medical Biophysics, University of Toronto, Toronto, ON Canada
6Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON Canada
7Saint John Regional Hospital, Saint John, MB, Canada
8Ontario Clinical Oncology Group, McMaster University, Hamilton, ON, Canada
9Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Edinburgh, UK
Melanie Spears, email: Melanie.Spears@oicr.on.ca
Keywords: breast cancer, chromosome instability, predictive biomarker, anthracycline, taxane
Received: February 17, 2016 Accepted: March 17, 2016 Published: April 1, 2016
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 fluorouracil (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.
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