Abstract: To determine the significance of ER and Ki-67 in the prognostication of locally advanced breast cancer patients treated with neoadjuvant chemotherapy. Methods: Data from 63 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy from 2006 to 2007 were analyzed. The expression of ER, HER-2, and Ki-67 were measured using immunohistochemistry. Auxiliary radiotherapy was performed in all these patients after surgery, and endocrine therapy was chosen based on the status of the hormone receptor. Results: Clinical complete responses or partial responses were achieved in 93.6% patients, and the side effects were well tolerated. There was no obvious correlation between the differences in biomarker expression and patient outcome. With a median follow-up time of 42 months, the significant parameters adversely influencing disease-free survival ( DFS ) at the univariate level in the log-rank tests were preoperative Ki-67 index ≥30%, ER ( - ) status before chemotherapy and after surgery, and postoperative HER-2( ++ )-( +++ ). At the multivariate level, a preoperative ER ( - ) status and postoperative HER-2 (++)-( +++ ) status were the significant prognostic factors for worse DFS ( P < 0.05 ). Conclusion: A preoperative ER ( - ) status is the most important prognostic factor; the Ki-67 index and ER status before chemotherapy might be more reliable indicators of the extent of malignancy.