A Study of Apatinib in Non-triple-negative Metastatic Breast Cancer

Inclusion Criteria: ●≥ 18 and ≤ 70 years of age. * ECOG performance status of 0-1. * Metastatic breast cancer, confirmed by histological analysis. * Have experienced at least 1 and at most 4 regimens, and failed from the last chemotherapy regimen. Pretreated anthracycline, taxanes and capecitabine (any rational reason for no use of capecitabine is acceptable) are mandatory. * Women diagnosed with human epidermal growth factor receptor positive (HER2+) should have failed for at least 1 anti-HER2 therapy (any rational reason for no use of anti-HER2 therapy is acceptable). HER2+ is defined as +++ staining on immunohistochemistry or FISH/CISH positive for gene amplification. * Women diagnosed with HR+ should have failed for at least 1 hormonal therapy. * Have failed for at least one chemotherapy regimen, but at most three regimens(including adjuvant and neo-adjuvant setting). * Duration from the last therapy (chemotherapy, radiotherapy, target therapy and operation) is more than 4 weeks (Duration for nitroso or mitomycin is 6 weeks). * Have at least one extracranial measurable site of disease according to RECIST 1.0 criteria that has not been previously irradiated. * Life expectancy of more than 3 months. * Negative serum or urine pregnancy test taken in all women within 7 days before inclusion. Sexually active women of childbearing potential must use a medically acceptable form of contraception from the beginning of the study to 8 weeks after the last dose of the investigated drug. * Written informed consent prior to study specific screening procedures. Exclusion Criteria: * Triple-negative breast cancer (ER-, PR- and HER2-. HER2- is defined as 0 or 1+ staining on immunohistochemistry or FISH/CISH negative for gene amplification. ) * Pregnant or lactating women. * Less than 4 weeks from the last clinical trial. * Uncontrolled hypertension with mono-drug therapy (\>140/90 mm Hg)；ischemia of the myocardium （≥ grade 2） or myocardial infarction；arrhythmia（≥ grade 2, QTcF \> 470ms for female patients） or New York Heart Association Class III/IV * Any factors that influence the usage of oral administration. * The cumulative doses of doxorubicin and epirubicin before inclusion have surpassed 300 mg/m2 and 600 mg/m2, respectively. * Duration from the last therapy (chemotherapy, radiotherapy, target therapy and operation) is less than 4 weeks (Duration for nitroso or mitomycin is less than 6 weeks). * Confirmed brain metastasis. * Inadequate hepatic, renal, heart, and hematologic functions (hemoglobin \<90g/L, neutrophils \< 1.5×10\^9/L, platelets \< 80×10\^9/L , ALT \> 2.5 x upper limit of normal (ULN)(5x for liver metastasis), AST \> 2.5 x ULN (5x for liver metastasis), serum bilirubin \> 1.5 x ULN, serum creatine \> 1.0 x ULN, creatinine clearance rate ≤ 50ml/min, LVEF \< lower limit of normal (LLN). * Abnormal coagulative function, inclined to bleeding or is receiving thrombolytictherapy or anticoagulation. * History of arterial/venous embolic events (such as cerebrovascular accident, TIA, deep vein thrombus,and pulmonary embolism) * Unhealed wound (\> 30 days) or bone fracture. * Urine protein ≥++ and confirmed \>1.0 g by the 24h quantity. * Previous or present history of pulmonary fibrosis,interstitial pneumonia,pneumoconiosis,radiation pneumonitis,drug-related pneumonitis or greatly-impaired pulmonary function. * Disability of serious uncontrolled intercurrence infection. * Abuse of alcohol or drugs. * Have received prior treatment with a VEGFR, PDGFR or s-SRC TKI (Bevacizumab is permitted). * Acquired or inherent immunodeficiency； HIV infection； organ transplantation history. * The active HBV or HCV infection or HBV DNA ≥10\^4/ml. * History of other malignancies except cured basal cell carcinoma of skin and carcinoma in-situ of uterine cervix. * Presence of serious harm to subjects or complication to hinder the completion of the study judged by investigators