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HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer : a meta-analysis of individual patient data
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HER2 TOP2A Meta-Anal Study Group (Including:
). (2011) HER2 and TOP2A as predictive markers for anthracycline-containing chemotherapy regimens as adjuvant treatment of breast cancer : a meta-analysis of individual patient data. Lancet Oncology, Vol.12 (No.12). pp. 1134-1142. doi:10.1016/S1470-2045(11)70231-5 ISSN 1470-2045.Research output not available from this repository.
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Official URL: http://dx.doi.org/10.1016/S1470-2045(11)70231-5
Abstract
Background: Prediction of response to anthracycline-based therapy for breast cancer is challenging. We aimed to assess the value of HER2 and TOP2A as predictive markers of response to anthracycline-based adjuvant therapy in patients with early breast cancer.
Methods: We did a meta-analysis of individual patient data from five randomised adjuvant trials that compared anthracycline-based regimens with cyclophosphamide, methotrexate, and fluorouracil (CMF) regimens. We assessed the status of HER2 and TOP2A genes with fluorescent in-situ hybridisation. Tumour samples were submitted to an external laboratory for validation. We calculated hazard ratios (HR) to compare event-free survival (EFS) and overall survival in patients receiving anthracycline-based treatment with those receiving CMF in two HER2 cohorts (HER2 amplified and non-amplified tumours) and in three TOP2A cohorts (normal, amplified, and deleted tumours).
Findings: We analysed data for 3452 patients for HER2 and 3102 patients for TOP2A. For EFS, HRs were 0.89 (95% CI 0.79-1.01) for HER2 non-amplified patients and 0.71 (0.58-0.86) for HER2-amplified patients (p(interaction) = 0.0485); for overall survival, HRs were 0.91 (95% CI 0.79-1.05) for HER2 non-amplified patients and 0.73 (0.59-0.89) for HER2-amplified patients (p(interaction) = 0.0718). In analysis of TOP2A status, HRs for EFS were 0.88 (0.78-1.00) for normal, 0.63 (0.46-0.87) for deleted, and 0.62 (0.43-0.90) for amplified (p(interaction) = 0.0513); HRs for overall survival were 0.89 (0.78-1.03) for normal, 0.68 (0.49-0.95) for deleted, and 0.67 (0.46-0.98) for amplified (p(interaction) = 0.1608). When patients with TOP2A-deleted and TOP2A-amplified tumours were grouped together (altered cohort) and compared with data from patients with normal TOP2A tumours, HRs for EFS were 0.64 (0.50-0.81) for altered and 0.88 (0.78-1.00) for normal (p(interaction) = 0.0183); HRs for overall survival were 0.67 (0.52-0.86) for altered and 0.89 (0.78-1.03) for normal (p(interaction) = 0.0455).
Interpretation: Although HER2 amplification and combined TOP2A amplification and deletion may have some value in the prediction of responsiveness to anthracycline-based chemotherapy, our findings do not support the use of anthracyclines only in patients with HER2-amplified or TOP2A-aberrated tumours.
Data sourced from Thomson Reuters' Web of Knowledge
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