OBJECTIVE The breast cancer lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) is defined as the Triple-negative breast cancer (TNBC). Our purpose is to compare the response and long-term effect of the TNBC and non-TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy, and to investigate the mechanisms of TNBC affecting the survivals. METHODS Data of long-term follow-up (median, 5.4 years) of 326 patients who received neo-adjuvant chemotherapy with anthracycline-based regimen, during a period from 2000 to 2003, were analyzed. Expressions of ER, PR, HER-2, P53, Ki-67 and E-cadherin were determined using immunohistochemical staining method. A multivariate Cox regression analysis was used to analyze independent prognostic factors affecting the relapse-free survival (RFS) and overall survival (OS) rates. Clinical effects of the neo-adjuvant anthracycline-based chemotherapeutic regimen and the RFS and OS rates were compared between the patients with TNBC and non-TNBC, and the correlations among the triple- negative phenotype (TNP), tumor grading and the expressions of P53, Ki-67 and E-cadherins were analyzed. RESULTS TNP, TNM staging, histological grades, clinical response of the neo-adjuvant chemotherapy and pathological complete remission (pCR) rate were the independent prognostic factors affecting the survival rates. Furthermore, 70 (21.5%) of the 326 patients suffered TNBC. Compared with the subjects in non- TNBC group, the patients with TNBC had a significantly higher pCR rate (P=0.046) and clinical response rate (P＝0.037), but also decreased 5-year RFS (P=0.001) and OS (P=0.004) rates. The RFS and OS rates were not improved in the TNBC patients who achieved a clinical remission after the neo-adjuvant chemotherapy. The triple-negative phenotype was positively correlated with the level of P53, Ki-67 expression (P＝0.007, P＝0.028), but negatively correlated with level of E-cadherin (P＝0.034).CONCLUSION Both clinical remission rate and pCR rate of the TNBC patients receiving neo-adjuvant anthracycline-based chemotherapy are high, however, the long-term effect is poor.The mechanism may relate to a strong potential of proliferation and invasive metastasis, as well as lack of an effective therapeutic target in the TNBC patients.