Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-70.0,  HER2 Positive Metastatic Breast Cancer Aged ≥18 and ≤70 years. 2. ECOG performance status of 0 to 1. 3. Life expectancy of more than 12 weeks. 4. According to 1.1, at least one measurable lesion exists 5. Histologically or cytologic confirmed HER2 positive metastatic breast cancer. 6. Prior treatment with trastuzumab (≥2 cycles in metastatic setting, or ≥3 months in adjuvant/neoadjuvant setting) and Taxane(≥2 cycles in any setting or untill unendurable AE or progression during treatment). 7. Previously reveived ≤2 chemotherapy regimens in metastasis setting; 8. Required laboratory values including following parameters: ANC: ≥ 1.5 x 10^9/L; Platelet count: ≥ 90 x 10^9/L; Hemoglobin: ≥ 90 g/L; Total bilirubin: ≤ 1.5 x upper limit of normal (ULN); ALT and AST: ≤ 2 x ULN(patients with liver metastases: ≤5 x ULN); BUN and Creatinine: ≤ 1x ULN;CCR≥50 mL/min;LVEF: ≥ 50%;QTcF: < 450 ms (male)，< 470 ms（female）; 9. Signed informed consent  Received capecitabine in metastatic setting; 2. Received HER2 targeted tyrosine kinase inhibitor (including Lapatinib, Neratinib and Pyrotinib); 3. Cumulated dosage of Doxorubincin >400 mg/m^2 or Epirubicin >800 mg/m^2 or equal dosage of other anthracycline drugs in adjuvant/neoadjuvant/metastatic setting ); 4. Received surgery，chemotherapy,radiotherapy or target therapy within 28 days prior to randomization. Received hormone therapy within 7 days prior to randomization; 5. Participated in other clinical trial within 28 days prior to randomization. 6. Known dihydro pyrimidine dehydrogenase（DPD）defect; 7. CT or MRI confirmed brain metastases; 8. Bone or skin lesion as unique target lesion; 9. Second malignancies within 5 years, except for cured skin basal cell carcinoma,carcinoma in-situ of uterine cervix and squamous-cell carcinoma; 10. Factors influencing the usage of oral administration (e.g. unable to swallow, chronic diarrhea and intestinal obstruction, etc.); 11. Uncontrolled third space effusion (such as pleural fluid and ascites) by drainage or other clinical intervention; 12. Receiving any other anti-tumour therapy after informed consent; 13. Unprogressed after or during the last anti-tumour therapy,according to 14. History of any kind of Heart disease,including 1)Angina pectoris; (2) Arrhythmia required medication or with clinical significance; (3) Myocardial infarction; (4) Heart failure; (5) Any other heart disease judged by researcher as not suitable for participating in this study, etc; 15. History of Immunodeficiency, acquired or congenital immunodeficiency (HIV positive) ,history of organ transplantation; 16. History of neurological or psychiatric disorders, including epilepsy or dementia; 17. Concomitant disease judged by investigators that may bring serious harm to the safety of patients or the completion of this study; 18. All female patients in breastfeeding period or in child-bearing period or with positive pregnancy test result or refusing to take a reliable method of birth control during the study; 19. Any other situations judged by investigator as not suitable for participating in this study