Evaluation of the prognostic/predictive value of HER2/TOP2A gene amplification and protein overexpression in patients with high-risk breast cancer treated with dose-dense sequential adjuvant chemotherapy.

e21059 Background: The prognostic/predictive value of HER2 and topoisomerase II alpha (TOP2A) gene status in patients with breast cancer treated with adjuvant dose-dense sequential chemotherapy is not well defined. Anthracyclines and taxanes are considered to be important drugs in this setting. Methods: Formalin-fixed tumor tissue samples were obtained from 354 patients participating in a phase III trial, in which 595 high-risk breast cancer patients were randomized to receive postoperative dose-dense sequential chemotherapy with epirubicin and CMF, with or without paclitaxel. HER2 and TOP2A gene amplification was evaluated by chromogen in situ hybridization (CISH) using ZYMED (InVitrogen) technology in 285 and 266 patients, respectively and protein expression was assessed by immunohistochemistry (IHC) in 297 and 248 patients, respectively. Results: Among the 52 tumors classified HER2-positive by IHC (3+, strong membranous staining in ≥30% of the tumor cells), 50 tumors (96%) were amplified by CISH. As fo...