Background Treatment option for metastatic breast cancer (MBC) patients pre-treated with chemotherapy is limited.Oral etoposide has shown some promises in these patients.However,patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure.This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.Methods MBC patients receiving at least two chemotherapy regimens prior to the enrollment were treated with repeated cycles of oral etoposide (60 mg.m-2.d-1 on days 1-10,followed by 11 days of rest).The primary end point was the progression free survival (PFS).The secondary end points were objective response rate (ORR),clinical benefit rate (CBR),overall survival (OS),and toxicity profiles.Results Thirty-two patients received 230 cycles of oral etoposide with a median of 6 cycles (range,2-20 cycles) per patient.Eight patients (25％) had partial response (PR) and 14 patients achieved stable disease (SD).The ORR was 25％.Nine patients achieved SD for more than 24 weeks and CBR was 53％.The median PFS and OS were 5 (range,1.5-17.0 months) and 16 months (range,3.0-51.0 months),respectively.The patients who achieved clinical benefit had longer survival time than those who did not (25.0 versus 11.0 months,P ＜0.01).Among the 16 patients who received more than four regimens prior to this study,four patients achieved PR and four achieved SD for more than 24 weeks,with a CBR of 50％.The most common hematologic adverse events were anemia (43.8％) and neutropenia (38.5％).Nausea/vomiting (75.0％) and alopecia (62.5％) were the most frequent non-hematologic toxicities.Conclusion Oral etoposide is effective and well tolerated in Chinese women with heavily pretreated MBC.