The Efficacy and Safety of Anlotinib Combined With Fulvestrant in Patients With Advanced Breast Cancer

Inclusion Criteria:

* Aged 18 years or older female；
* ECOG score 0-1;
* Life expectancy is not less than 12 weeks;
* Histology confirmed HR-positive and HER2-negative locally advanced or metastatic breast cancer;
* Premenopausal women have taken effective ovarian function suppression methods, such as drug suppression or ovariectomy;
* At least one objectively measurable breast cancer lesions according to RECIST 1.1 ;
* No more than one systemic chemotherapy for metastatic disease;
* Disease relapse within 12 months after at least 24 months endocrine adjuvant therapy, or disease progress after at least 6 months endocrine salvage therapy;
* Normal function of main organs and bone marrow: Hemoglobin≥90g/L; Neutrophil count (ANC)≥1.5×109/L; Platelet count (PLT)≥80×109/L; Total bilirubin≤1.5×ULN (upper limit of normal); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (≤5×ULN if has liver metastasis); Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60mL/min (Cockcroft-Gault formula);
* Sign the informed consent;

Exclusion Criteria:

* Have received prior fulvestrant or anti-angiogenic drug treatment, or known to be allergic to any excipients in the study;
* Visceral crisis;
* Uncontrolled or high-burden CNS metastases;
* Unable to swallow;
* Abnormal coagulation function;
* Tumor has invaded important blood vessels and may cause fatal bleeding;
* Pleural effusion or pericardial effusion that requiring repeated drainage;
* Hypertension that cannot be well controlled by a single antihypertensive drug;
* Unstable angina, myocardial infarction within 6 months, serious arrhythmias;
* The history of immunodeficiency, including HIV or other obtained or congenital immunodeficiency diseases, or a history of organ transplantation;
* Poorly controlled diabetes;
* Abnormal urine protein, and the 24-hour quantification suggests urine protein ≥1.0g;
* Bleeding constitution or medical history
* Unhealed wounds, ulcers or fractures;
* Have arterial/venous thrombotic events within 6 months, such as cerebrovascular accidents (including temporary ischemic attacks), deep vein thrombosis and pulmonary embolism;
* In other clinical trials of anti-tumor drugs simultaneously;
* Other concomitant disease or disability that endangers safety according to the judgment of investigator;