Topoisomerase II alpha (TopoIIa) and MAPtau: Potential predictive markers of response in locally advanced breast cancer (LABC) treated with epirubicin and docetaxel (ET) in neoadjuvant setting.

Abstract

57 Background: Neoadjuvant chemotherapy can achieve a high objective response rate in patients with LABC. This allows breast conservation surgery in those patients who are initially not suitable for this procedure. The patients who mainly benefit from neoadjuvant chemotherapy are those who achieve a pathological complete response (pCR) with no residual microscopic tumour. This occurs in only 3–16% of patients, who have substantially improved disease-free survival (DFS) and OS compared to those with pathological evidence of residual cancer. In order to identify patients most likely to achieve benefit from neoadjuvant chemotherapy, it would be useful to identify predictors of pCR. ET is a valid doublet therapy in the neoadjuvant setting; Topo-IIa and MAP-Tau are the principal targets of anthracyclines and taxanes, respectively. We evaluated a possible role of the two proteins in predicting a pathological response rate in LABC. Methods: TopoIIa and MAPtau expression was evaluated by immunohistochemistry (IHC) in tumour biopsy from 22 women with LABC treated with ET as neoadjuvant chemotherapy, and protein levels were correlated to the outcome. Results: TopoIIa over-expression was significantly associated with ductal histology (58.3% in ductal carcinoma vs 0% in other hystotypes, p=.038) and hormone receptors (HRs) expression (63.6% in HR+ vs 0% in HR- tumours), whereas no significant correlation was observed with HER2 expression. MAP-tau did not correlate with histology, grading, HRs and HER2 status. Pathological complete response (pCR) rate was higher in tumours with MAPtau low/normal expression compare to those over-expressing the protein (36.4% vs. 14.3%), although not significantly. Pts with TopoIIa over-expression achieved a significantly higher pCR rate than those with a low/normal expression (57.1% vs. 9.1%; p=.047). Data on the RFS are not available because of the short period of follow-up. Conclusions: IHC evaluation of TopoIIa might be useful in identifying pts potentially responsive to neoadjuvant chemotherapy with anthracyclines and taxanes. Data on RFS will be available later.