Prognostic and predictive value of the combination of TOP2A and HER2 in node-negative tumors 2cm or smaller (T1N0) breast cancer.

Abstract

We aim to evaluate the prognostic and predictive value of TOP2A and HER2 expression in T1N0 breast cancer patients. 299 cases with T1N0 breast cancer were obtained from the Oncomine database (Cohort 1) and 963 of T1N0 breast cancer patients from Sun Yat-sen Memorial Hospital (Cohort 2) were retrospectively enrolled. Kaplan-Meier product was applied to estimate survival curve. Cox proportional hazard models was used to identify prognostic factors. We used PSM (propensity score matching) to balance clinicopathologic characteristics among four groups of different HER2/TOP2A status. Survival between groups and chemotherapy regimens were analyzed, before and after PSM. In Cohort 1, we found that the group with HER2+ and higher expression of TOP2A mRNA was associated with poor breast cancer-specific survival (BCSS) compared to the group of HER2- with lower expression of TOP2A mRNA. In Cohort 2, HER2+ patients with higher TOP2A protein expression had greater risk of recurrence and distant recurrence compared to HER2- patients with lower expression of TOP2A protein. Among the patients who developed both HER2+ and higher expression of TOP2A protein and received chemotherapy, patients who received an anthracycline-based regimen had a significantly better recurrence-free survival (RFS) than those with a non-anthracycline-based regime. Patients with both HER2+ and high expression level of TOP2A protein predicts poor prognosis in T1N0 breast cancer patients. Patients with double positive for TOP2A protein and HER2 may benefit from anthracycline-based regimens.