The role of topoisomerase IIa in predicting sensitivity to anthracyclines in breast cancer patients: a meta-analysis of published literatures

Topoisomerase IIa is not only a proliferation marker of tumor cells, but is also a target for anthracyclinebased chemotherapy. Both in vitro and in vivo studies have shown that there is a relationship between topo IIa and chemosensitivity to anthracyclines, but the predictive role of topo IIa in breast cancer patients is still controversial. A meta-analysis based on published studies was performed to obtain an accurate assessment of the association between topo IIa and sensitivity to anthracycline-based chemotherapy. A total of 13 eligible studies, including 2,633 cases and 2,118 controls were identified. Topo IIa was associated with sensitivity to anthracyclines in locally advanced breast cancer patients who received neoadjuvant chemotherapy [five studies, including three using fluorescence in situ hybridization (FISH) and two using immunohistochemistry (IHC): relative risk (RR) = 1.93, 95% confidence interval (95% CI): 1.27–2.94, P = 0.002; two using FISH and three using IHC: RR = 1.98, 95% CI: 1.37–2.86, P\0.001]. This association existed among three studies using FISH (RR = 2.03, 95% CI: 1.14–3.61, P = 0.017), but did not exist among three studies using IHC (P[0.05). In earlystage breast cancer patients who received anthracyclinebased adjuvant chemotherapy compared with non-taxanebased polychemotherapy, amplification [hazard ratio (HR) = 0.64, 95% CI: 0.49–0.83, P = 0.001; HR = 0.59, 95% CI: 0.35–1.01, P = 0.056] or deletion (HR = 0.82, 95% CI: 0.67–1.00, P = 0.051; HR = 0.58, 95% CI: 0.35–0.97, P = 0.036) of topo IIa was significantly associated with better recurrence-free survival and overall survival. In summary, the present meta-analysis suggests that topo IIa is a predictive factor for breast cancer patients who receive anthracycline-based chemotherapy. Larger and well-designed prospective studies are required to further evaluate the predictive role of topo IIa in clinical practice.