Effect of dose intensity and overexpression of topoisomerase iia on survival in patients with locally advanced breast cancer treated with anthracyclines

Abstract

11512 Background: TopoIIa is a therapeutic target of anthracyclins, its predictive and prognostic value in breast cancer is being evaluated. The aim of this study was to determine the effect of anthracycline dose intensity in terms of overall(OS) and free disease survival (DFS) in patients with over expressing TopoIIa. Methods: TopoIIa expression in locally advanced breast cancer samples that receive neoadjuvant treatment with doxorubicin were evaluated. Expression of TopoIIa was determined by immunohistochemistry in samples embedded in paraffin. Patients expressing TopoIIa were clustered according to the dose intensity of doxorubicin (≤ 24 or > 24 mg/m2/week). Survival curves were determined by Kaplan-Meier test and the comparations with the Logrank test. Results: 109 samples were evaluated. 40/109 (36.7%) over express TopoIIa, there was no differences in clinical characteristics in both groups. In patients TopoIIa positive, the median to age was 47 years (range: 33–74), Postmenopausal 30/40 (75%), ductal carcinoma 37/40 (92.5%) and lobulillar carcinoma 3/40 (7.5%). Positive estrogen receptors: 18/40 (45%) and positive progesterone receptor: 11/40 (27.5%). High proliferation index of expression of Ki-67 (≥40%) in 21/35 (40%) and HER2 positive in 10/37 (27%). Dose intensity of doxorubicin: ≤ 24 mg/m2/week in 15/40 (37.5%) and > 24 mg/m2/week in 25/40 (62.5%). Results of efficacy are showed in the follow table: Conclusions: Patients with locally advanced breast cancer and over expression of TopoIIa receiving a dose intensity > 24 mg/m2/week present a better survival than patients receiving lower dose intensities. Total < 24 mg/m2/week > 24 mg/m2/week p DFS Median 30 months 16 months 63 months 0.010 5 years OS 38% 13% 50% Median 32 months 27 months 57 months 0.027 5 years 35 % 14 % 45 % No significant financial relationships to disclose.