Prognostic Significance of TOP2A Gene Dosage in HER-2-Negative Breast Cancer

Abstract

Previous studies showed the prognostic and predictive impact of human epidermal growth factor receptor 2 (HER-2) gene alterations analyzed separately and jointly with topoisomerase II α (TOP2A) gene alterations; however, the role of TOP2A gene abnormalities alone has not been thoroughly investigated. Additionally, TOP2A aberrations were typically studied in HER-2-positive (HER-2(+)) tumors because these genes are frequently coamplified. Therefore, the knowledge concerning the impact of TOP2A abnormalities in HER-2-negative (HER-2(-)) patients is scarce. This study aimed to investigate the clinical significance of TOP2A anomalies in breast cancer patients with HER-2(-) and HER-2(+) tumors. Snap-frozen tumor samples from 322 consecutive stage I-III breast cancer patients were analyzed for TOP2A gene dosage using quantitative real-time PCR (qPCR). A high TOP2A gene dosage was found in 94 tumors (29%)-32% and 27% of HER-2(+) and HER-2(-) tumors, respectively. The mean TOP2A gene dosages in the HER-2(+) and HER-2(-) groups were 1.49 ± 1.03 and 1.09 ± 0.35, respectively. High TOP2A gene dosage had an inverse prognostic impact in terms of shorter disease-free survival (DFS) and overall survival (OS) times in the entire group and in both the HER-2(-) and HER-2(+) subgroups. The unfavorable prognostic impact of TOP2A gene dosage was maintained in the multivariate Cox regression analysis in the entire group and in HER-2(-) patients. A high gene dosage of TOP2A determined using qPCR occurs frequently both in HER-2(+) and HER-2(-) tumors and has a strong adverse prognostic impact.