The Library
Predicting anthracycline benefit : TOP2A and CEP17-not only but also
Tools
Tools
Tools
Bartlett, J. M. S., McConkey, Christopher C., Munro, A. F., Desmedt, C., Dunn, Janet A., Larsimont, D., O'Malley, F. P., Cameron, D. A., Earl, H., Poole, Christopher J., Shepherd, L. E., Cardoso, F., Jensen, M., Caldas, C., Twelves, C. J., Rea, D. W., Ejlertsen, B., Di Leo, A. and Pritchard, K. I. (2015) Predicting anthracycline benefit : TOP2A and CEP17-not only but also. European Journal of Cancer Care, 33 (15). pp. 1680-1687. doi:10.1200/JCO.2013.54.7869
An open access version can be found in:
Official URL: https://doi.org/10.1200/JCO.2013.54.7869
Abstract
Purpose
Evidence supporting the clinical utility of predictive biomarkers of anthracycline activity is weak, with a recent meta-analysis failing to provide strong evidence for either HER2 or TOP2A. Having previously shown that duplication of chromosome 17 pericentromeric alpha satellite as measured with a centromere enumeration probe (CEP17) predicted sensitivity to anthracyclines, we report here an individual patient-level pooled analysis of data from five trials comparing anthracycline-based chemotherapy with CMF (cyclophosphamide, methotrexate, and fluorouracil) as adjuvant chemotherapy for early breast cancer.
Patients and Methods
Fluorescent in situ hybridization for CEP17, HER2, and TOP2A was performed in three laboratories on samples from 3,846 of 4,864 eligible patients from five trials evaluating anthracycline-containing chemotherapy versus CMF. Methodologic differences did not affect HER2-to-CEP17 ratios but necessitated different definitions for CEP17 duplication: > 1.86 observed copies per cell for BR9601, NEAT, Belgian, and DBCG89D trials and > 2.25 for the MA.5 trial.
Results
Fluorescent in situ hybridization data were available in 89.3% (HER2), 83.9% (CEP17), and 80.6% (TOP2A) of 3,846 patient cases with available tissue. Both CEP17and TOP2A treatment-by-marker interactions remained significant in adjusted analyses for recurrence-free and overall survival, whereas HER2 did not. A combined CEP17 and TOP2A-adjusted model predicted anthracycline benefit across all five trials for both recurrence-free (hazard ratio, 0.64; 95% CI, 0.51 to 0.82; P = .001) and overall survival (hazard ratio, 0.66; 95% CI, 0.51 to 0.85; P = .005).
Conclusion
This prospectively planned individual-patient pooled analysis of patient cases from five adjuvant trials confirms that patients whose tumors harbor either CEP17 duplication or TOP2A aberrations, but not HER2 amplification, benefit from adjuvant anthracycline chemotherapy. (C) 2015 by American Society of Clinical Oncology
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School |
||||
| Journal or Publication Title: | European Journal of Cancer Care | ||||
| Publisher: | Wiley-Blackwell Publishing Ltd. | ||||
| ISSN: | 0961-5423 | ||||
| Official Date: | 20 May 2015 | ||||
| Dates: |
|
||||
| Volume: | 33 | ||||
| Number: | 15 | ||||
| Page Range: | pp. 1680-1687 | ||||
| DOI: | 10.1200/JCO.2013.54.7869 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Open Access Version: |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
