Correlation of TOP2A expression in HER2-positive breast cancer with pathologic response and clinical outcomes in patients undergoing neoadjuvant treatment based on anthracycline.

Abstract

643 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. TOP2A (a target of anthracyclines) and HER2 genes are both amplified in 40% of breast cancers. Data from literature are conflicting regarding the potential of TOP2A as a predictor of response to anthracyclines. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy and evaluated nuclear TOP2A protein expression in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2011, data from 82 patients was reviewed. Forty nine patients had the paraffin blocks corresponding to the pre-treatment biopsy. All biopsies had some degree of TOP2A IHC expression. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 10%. This was found in 77.6% of cases. Forty percent of the patients achieved pathologic complete response in pos-treatment surgical specimens. Correlation was observed between TOP2A IHC expression and tumor pathological response (p0.02). It was observed a difference in pathological complete response in favour of the group positive for TOP2A (47.4% vs. 22.7%), although not significant (p=0.09). No difference in PFS and OS was observed between patients with complete response after median follow-up of 34 months. Conclusions: The expression of TOP2A seems to be a promising marker to predict pathological response to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer; however these findings would be better evaluated in prospective trials.