Clinical Assistant Professor Hanyang University Hospital, Republic of Korea
Introduction Topoisomerase-II-alpha (TOP2A) has been considered a biomarker for tumor proliferation and its overexpression is known to be associated with aggressiveness of breast cancer. However, its prognostic implication has not been well studied. We aimed to investigate the prognostic implication of TOP2A overexpression according to molecular subtype in patients with primary breast cancer. Methods Clinical information and tissue blocks were obtained retrospectively from 193 patients with invasive breast cancer who underwent curative surgery at single institution between 2002 and 2017. Immuno-histochemical staining for TOP2A was performed on formalin-fixed paraffin-embedded samples using mouse monoclonal antibody. TOP2A overexpression was defined as ≥ 30% of tumor cells stained positive. Overall survival was analyzed by Kaplan Meier analysis and Cox regression model. Results Among 193 patients with invasive breast cancer, 56 (29.0%) patients had TOP2A overexpression. Large tumor size, axillary node metastasis, poor grade, high Ki-67 index (>20%), and triple negative subtype were significantly associated with overexpression (P < 0.0001). After median follow up of 70 months, TOP2A overexpression was related with poor prognosis in patients with HER2-positive subtype (5-year overall survival rate; 77.4% vs. 93.8%, Log-rank P = 0.032). In a Cox proportional hazards model, TOP2A overexpression was the most significant prognostic factor in patients with HER2-positive subtype after adjustment of hormone receptor status and use of chemotherapy (hazard ratio; 10.413, 95% confidence interval [1.07-101.49], P = 0.044, table 1). Conclusion TOP2A overexpression is a poor prognostic factor in patients with HER2-positive breast cancer and could be used as a potential biomarker for risk stratification. More studies are warranted to suggest the escalating strategy of systemic therapy or local treatment for those patients.