Eribulin is the promising agent for late-line metastatic breast cancer patients. The aim of this Phase II, double-arm, open-label and prospective clinical trial is to assess the efficacy and safety of Eribullin or Eribulin combined with Anlotinib in patients with metastatic breast cancer

The aim of the double-arm, open-label, phase II clinical trial is to assess efficacy and safety of Eribulin or Eribulin combined with Anlotinib in metastatic breast cancers. The investigator hypothesize that both Eribulin and Eribulin combined with Anlotinib may be an effective alternative treatment for metastatic breast cancers. In addition, Eribulin combined with Anlotinib might be able to improve the treatment response and progression-free survival.

Inclusion Criteria:

• Age ≥ 18 years old, voluntary consent and signed written informed consent
• ECOG 0~2
• Pathologically diagnosed HER2-negative breast cancer patients with radiologically confirmed locally advanced (stage IIIB or IIIC) or metastatic (stage IV) breast cancer; HR-positive patients were permitted
• At least one measurable disease lesion before treatment
• Never receive Eribulin Mesylate treatment or anti-angiogenetic therapies before recruitment
• Anticipated survival time is longer than three months
• Brain metastases with stable disease or without clinical symptom
• Blood routine test, liver and kidney function test meet the following criteria: PLT > 100g / L, Hb > 9g / L, Neutrophil > 2.0 g/L; AST and ALT < 2.5 upper limit of normal (ULN); Cr < 1.0 ULN; TBIL < 1.5ULN
• Previously treated with anthracycline-based and taxane-based chemotherapy regimens (at least one line of chemotherapy in the metastatic setting or the recurrence time is less than 1 year from the end of adjuvant or neoadjuvant chemotherapy); for HR-positive/HER2-negative patients, progressed after at least one line of endocrine therapy
• For women with fertility, the pregnancy test before administration was negative, and agreed to take appropriate measures to avoid pregnancy during the study treatment and at least half a year after the end of treatment; Men agreed to take appropriate contraceptive measures during the study treatment and at least half a year after the end of the treatment.

Exclusion Criteria:

• Pregnant or lactating women
• Active infection requiring systemic treatment
• HIV positive
• Suffering from or suspected of suffering from central neuromuscular system diseases
• Serious heart disease; uncontrollable hypertension; history of heavy hemorrhea；recent operation within three months
• The investigator considered that the patient was not suitable for in this study, with any other situation.