Anthracycline-based chemotherapy is commonly used in the adjuvant or neoadjuvant setting of breast cancer.Topoisomerase ⅡA has been suggested as a possible predictive factor of response to anthracyclines.Ki-67 is frequently measured to estimate the proliferative activity of tumor cells, and potentially could be a predictor of chemotherapeutic efficacy.We analyzed the relationship between the expression of topoisomerase ⅡA and Ki-67 in the breast cancer and its regression as induced by neoadjuvant chemotherapy, and examined if topoisomerase ⅡA and Ki-67 were associative predictors of the response.Methods: From May 2005 until January 2009, 38 patients who underwent neoadjuvant chemotherapy were examined.Prior to chemotherapy, we had obtained specimens by core needle biopsy,and measured the expression of topoisomerase ⅡA protein and Ki-67 with immunohistochemical staining, and determined the gene copy number of topoisomerase ⅡA by fluorescence in situ hybridization.We measured the sizes of tumors (maximum length+vertical length) with images of MRI and CT before and after the chemotherapy, and subsequently calculated the reduction rate of the tumors.Results: Topoisomerase ⅡA expression significantly correlated with the expression of Ki-67 in breast cancer (r2=0.5107, p<0.01).In the cohort of high expression of topoisomerase ⅡA protein (topoisomerase ⅡA≥25%), the reduction rate was significantly higher than that observed in the cohort of lower expression of topoisomerase ⅡA protein (topoisomerase ⅡA<10%).There was an association between Ki-67 and the reduction rate, but it was not statistically significant.There was no association between the gene copy number of topoisomerase ⅡA and reduction rate.Conclusion: Topoisomerase ⅡA protein overexpression can predict benefits of treatment with an thracyclines in the neoadjuvant setting of breast cancer.