Abstract: Objective:To observe the clinical efficacy and safety of apatinib combined with chemotherapy in the patients with advanced breast cancer after failed multi-line therapy, and to clarify the siginificance of apatinib in the treatment of the patients with advanced breast cancer. Methods:Twenty-five patients with advanced breast cancer were treated with multi-line therapy,among them 5 (20%) patients were in the third-line treatment, 7 (28%) patients were in the fourth-line treatment, and 13 (52%) patients were in the fifth-line treatment and above. All patients were treated with apatinib in combination with chemotherapy, and the chemotherapy regimen was selected based on the condition and previous medication. Apatinib 250-500 mg was given orally once a day, until the disease progresses occured or the patients could not tolerate the adverse reactions. The efficacies, including the objective response rate(ORR), the clinical benefit rate(CBR), and progression-free survival (PFS), were evaluated by RECIST 1.1. The adverse reactions were evaluated by NCI-CTC 4.0. Results:The median number of treatment lines of the patients with breast cancer was fifth-line, the total ORR was 12% (3/25), the CBR was 52% (18/25), and the median progression-free survival (mPFS) was 6.00 months. Among the 5 patients with third-line therapy, 2 patients were stable disease(SD) and the CBR was 40% (2/5); among the 7 patients received the fourth-line therapy, 2 patients were partial response(PR), 2 patients were SD, and the CBR was 57%(4/7); among the 13 patients received firth-line therapy, 1 patient was PR, 6 cases were SD, and the CBR was 54% (7/13). According to the pathological type, among 5 patients of triple-negative type, 3 patients were SD, the CBR was 60% (3/5); among 12 patients of Luminal type,1 patients was PR, 2 patients were SD, and the CBR was 25% (3/12); among 8 patients of HER-2 positive type, there were 2 patients acheived PR, 5 patients acheived SD, and the CBR was 88% (7/8). The short-term efficacy of the patients in 50 years old and over group was better than that of the patients in below 50 years old group (P<0.05). There were no significant differences in the short-term efficacies between the other factors (P>0.05). Moreover, the patients treated with apatinib combined with chemotherapy had good tolerance, and the main adverse reactions were fatigue, hand-foot syndrome, hepatic insufficiency, hypoproteinemia, anemia, anepi-thymia,hypertension,and proteinuria;mainly in grade 1 or grade 2;the most common adverse reactionswere fatigue(80%),hypoproteinemia(60%),hand-foot syndrome(60%),and hepatic insufficiency(60%). Conclusion:Apatinib mesylate combined with chemotherapy is effective in the treatment of the advanced breast cancer patients failed in multi-line therapy and the patients can tolerate the adverse reactions.

Key words: breast neoplasms, apatinib, chemotherapy, objective response rate, clinical benefit rate, progression-free survival