532 Background: The primary objective of the study was to evaluate TOP2A as predictive marker for adjuvant treatment with epirubicin in high-risk breast cancer patients. As a secondary objective the prognostic characteristics of TOP2A gene aberrations was investigated. The data presented on the predictive properties is a follow-up to the data previously published (Knoop et al, J Clin Oncol 2005; 23: 7483–90). Methods: 962 pre- and postmenopausal high-risk Danish patients were enrolled in the DBCG89D protocol. The patients were randomly allocated to either 9 × CMF (cyclophosphamide, methotrexate, 5-flurouracil) (n=495) or 9 × CEF (cyclophosphamide, epirubicin, 5-flurouracil) (n=467) every 3 weeks. Tumor-tissue was available from 806 patients (84%). The tumors were analyzed for TOP2A copy number changes with the TOP2A FISH pharmDx Kit (Dako, Glostrup). Recurrence-free survival (RFS) was used as primary end-point. Univariate and multivariate statistics were used to assess the predictive and prognostic properties of the TOP2A gene aberrations. Results: The TOP2A test was successful in 96% of the patients. Ninety-two (12.0%) patients were found to have TOP2A amplified tumors, and 86 (11.1%) to have TOP2A deleted tumors. For the primary study endpoint (RFS) a significant predictive value of TOP2A gene amplifications was found (HR=0.39; CI: 0.22–0.70; p=0.0017). A similar trend was seen with respect to TOP2A deletions (HR=0.61; CI: 0.35–1.07; p=0.082). TOP2A gene aberrations were significantly associated with several established prognostic factors and had independent prognostic value, associated with a significant worse prognosis both for RFS (p=0.036) and overall survival (p=0.012). Conclusions: The DBCG89D study has shown that TOP2A amplifications are associated with a favorable outcome of adjuvant treatment with epirubicin in primary breast cancer. Further, TOP2A aberrations demonstrated an independent prognostic value. [Table: see text]
Impairment of Cognitive Function in Women Receiving Adjuvant Treatment for High-Risk Breast Cancer: High-Dose Versus Standard-Dose Chemotherapy