Final results of a meta-analysis testing HER2 and topoisomerase IIα genes as predictors of incremental benefit from anthracyclines in breast cancer

519 Background: Five trials comparing anthracyclines (A) with CMF in the early setting tested HER2 and topoisomerase IIα (TOP2A) genes as predictors of benefit from A. An interim report of this meta-analysis suggested that both genes are clinically modest predictors (SABCS 2008 abs 705). Methods: HER2 and TOP2A were tested in four national laboratories by FISH (amplification: ratio ≥2; TOP2A deletion: ratio ≤ 0.8). National lab (NL) scores were validated by submitting randomly selected cases to a central lab (CL) for FISH (Abbott labs, USA). Individual patient data were centralized. Onsite visits were performed. Results: Final results are based on 3,452 and 3,102 pts for HER2 and TOP2A, respectively. HER2 NL scores were validated in 137 cases (discordance 8/137, 5.8%), TOP2A NL scores in 123 cases (discordance 38/123, 30.9%). Conclusions: HER2 and TOP2A genes have clinically modest and statistically borderline predictive value. Some HER2-negative pts derive benefit from A. Disease-free survival (DFS) haza...