CEP17 or TOP2A Aberrations Predict Benefit of Adjuvant Anthracycline-Based Chemotherapy in Breast Cancer
In a study reported in the Journal of Clinical Oncology, Bartlett et al found that the presence of duplication of chromosome 17 pericentromeric alpha satellite, measured by a centromere enumeration probe (CEP17), and TOP2A aberrations predicted benefit of anthracycline-based adjuvant therapy in early breast cancer.
Study Details
The study was an individual patient-level pooled analysis of data from five trials comparing adjuvant anthracycline-based chemotherapy vs CMF (cyclophosphamide, methotrexate, and fluorouracil). Fluorescence in situ hybridization for CEP17, HER2 amplification, and TOP2A was performed in samples from 3,846 of 4,864 eligible patients, with data successfully obtained in 89.3% for HER2, 83.9% for CEP17, and 80.6% for TOP2A.
Predictors of Benefit
In analysis adjusting for clinicopathologic variables, treatment by marker interactions was significant in favor of anthracycline treatment for CEP17 for recurrence-free survival (hazard ratio [HR] = 0.67, P = .002) and overall survival (HR = 0.71, P = .01) and for TOP2A for recurrence-free survival (HR = 0.67, P = .005) and overall survival (HR = 0.67, P = .008) but not for HER2 for either recurrence-free survival (HR = 0.81, P = .11) or overall survival (HR = 0.80, P = .10).
A combined CEP17 and TOP2A-adjusted model predicted anthracycline benefit across all five trials for both recurrence-free (HR = 0.64, P = .001) and overall survival (HR = 0.66, P = .005).
The investigators concluded: “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.”
John M. S. Bartlett, PhD, of Ontario Institute for Cancer Research, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by the Ontario Institute for Cancer Research, and data gathering was supported in part by the Brussels Region BruBreast Project, Cancer Research UK, and Scottish Breast Cancer Clinical Trials Group. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
