This is a study to compare the antitumor activity of ramucirumab (IMC-1121B) and eribulin together versus eribulin alone, in participants with locally recurrent or metastatic breast cancer.

Inclusion Criteria:

• Have histologically or cytologically confirmed invasive breast cancer which at the time of study entry is either locally recurrent disease not amenable to curative therapy or Stage IV disease (American Joint Committee on Cancer Staging Criteria for breast cancer)
• Have measurable and/or nonmeasurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Have received at least 2 but not more than 4 prior cytotoxic chemotherapy regimens in the locally recurrent or metastatic setting
• Have received prior treatment with both anthracyclines and taxanes, either in the metastatic, adjuvant or neoadjuvant setting
• Have received Human Epidermal Growth Factor Receptor 2 (HER-2) directed treatment; or are not a candidate for HER-2-directed treatment if the patient has HER-2 positive disease
• Have completed any prior radiotherapy and/or hormonal therapy at least 1 week prior to randomization and have recovered from all clinically significant treatment-related toxicities
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Have left ventricular ejection fraction within normal limits
• Have discontinued all previous chemotherapy treatments for cancer at least 3 weeks prior to randomization and recovered from clinically significant toxic effects
• Have resolution to Grade less than or equal to 1 [by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0] of all clinically significant toxicities of prior chemotherapy, surgery, radiotherapy, or hormonal therapy with the exception of peripheral neuropathy, which must have resolved to Grade less than or equal to 2
• Have adequate hematologic, hepatic, renal, and coagulation function
• Test negative for pregnancy
• Have a life expectancy of at least 3 months

Exclusion Criteria:

• Have a concurrent active other malignancy other than adequately treated non-melanomatous skin cancer or other noninvasive or in situ neoplasms
• Are currently enrolled in, or recently discontinued from, a clinical trial involving an investigational product, or concurrently enrolled in any other type of medical research judged not to be medically compatible with the study
• Have received investigational therapy within 3 weeks prior to randomization
• Have received prior ramucirumab or eribulin
• Have a known sensitivity to agents of similar biologic composition as ramucirumab, halichondrin B and/or halichondrin B chemical derivative
• Have received bevacizumab within 6 weeks prior to randomization
• Have uncontrolled or poorly controlled hypertension
• Have congenital prolonged QTc syndrome (or have a family history) or prolongation of QTc at baseline
• Have a history of additional risk factors for torsades de pointes within the last year prior to randomization
• Have an implantable pacemaker or automatic implantable cardioverter defibrillator
• Have bradycardia
• Have an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention within 6 months prior to randomization
• Have a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
• Have experienced a Grade 3 or greater bleeding event within 3 months prior to randomization
• Have experienced any Grade 3 or greater arterial thromboembolic events within 6 months prior to randomization, or venous thromboembolic event within 3 months prior to randomization
• Have undergone major surgery within 4 weeks prior to randomization or subcutaneous venous access device placement within 7 days prior to randomization
• Have a planned major surgery to be performed during the course of the trial
• Have uncontrolled metabolic conditions
• Have an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
• Have known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• Have pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment including the use of oxygen
• Have received a prior allogeneic organ or tissue transplantation
• Have had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
• Have known leptomeningeal metastases
• Have cirrhosis (Child-Pugh Level B or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites