Abstract: Objective To evaluate the biological marker status during breast cancer progression for long-term survival patients with breast cancer in China. Methods One hundred and sixty-eight breast cancer patients with a long-term follow-up time (more than 5 years) were collected. The tissue samples from 27 patients with metachronous recurrence were obtained. HER-2, ER and PR status were detected by immunohistochemistry or Her-2 gene amplification by fluorescence in situ hybridization. The relationships between HER-2 and HR expression and the relationships between the original treatments and the secondary chemotherapy for recurrence were evaluated. Results We obtained 27 samples from 36 recurrence patients. For metachronous recurrence metastases, the HER-2 status changed in 18.5% （5/27）. Three patients changed from positive to negative, while 2 patients converted from negative to positive. A change in ER status was observed in 7 cases (25.9%): 5 cases from positive to negative and 2 cases from negative to positive. PR status changed in 2 cases from positive to negative and in 0 case from negative to positive. There was no significant correlations between the changes of HER-2 and the initial radiochemotherapy, anti-HR therapy.However, it was involved in down-regulation of HR expression(Fisher exact test=0.026）.In Kaplan-Meier analysis, patients with changes of HER-2 or HR expression had a mildly poor response to chemotherapy and progress-free survival （33.4 vs. 38.6 months, Log-rank=1.96, P=0.16）, compared with the patients without changes. Conclusion HER-2 and HR status had been changed during breast cancer progression in the metachronous recurrence patients.So it is necessary to re-evaluate those biomarkers should be neoplastic tissue from metastatic site, whenever possible,for the recurrence patients.