title: A four gene signature of chromosome instability (CIN4) predicts for benefit from taxanes in the NCIC-CTG MA21 clinical trial.
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.
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Spears
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.
authors.forename: Nicola
authors.initials: N
authors.lastname: Lyttle
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.|Informatics and Bio-Computing, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.
authors.forename: Alister
authors.initials: A
authors.lastname: D'Costa
authors.affiliation: NCIC Clinical Trials Group (NCIC CTG) and Queen's University, Kingston, ON, Canada.
authors.forename: Bingshu E
authors.initials: BE
authors.lastname: Chen
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.|Informatics and Bio-Computing, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.
authors.forename: Cindy Q
authors.initials: CQ
authors.lastname: Yao
authors.affiliation: Informatics and Bio-Computing, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON Canada.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: Saint John Regional Hospital, Saint John, MB, Canada.
authors.forename: Margot
authors.initials: M
authors.lastname: Burnell
authors.affiliation: Ontario Clinical Oncology Group, McMaster University, Hamilton, ON, Canada.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Levine
authors.affiliation: NCIC Clinical Trials Group (NCIC CTG) and Queen's University, Kingston, ON, Canada.
authors.forename: Patti
authors.initials: P
authors.lastname: O'Brien
authors.affiliation: NCIC Clinical Trials Group (NCIC CTG) and Queen's University, Kingston, ON, Canada.
authors.forename: Lois
authors.initials: L
authors.lastname: Shepherd
authors.affiliation: Transformative Pathology, Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON, Canada.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.|Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Edinburgh, UK.
authors.forename: John M S
authors.initials: JM
authors.lastname: Bartlett
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D043171:Chromosomal Instability; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D043823:Taxoids / Q000737:chemistry*
chemical_list: D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D043823:Taxoids; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil
keywords: anthracycline; breast cancer; chromosome instability; predictive biomarker; taxane