Inclusion Criteria:

• Signed study-specific Informed Consent Form(s)
• Age ≥ 18 years
• Histologically documented breast cancer
• HER2-positive disease
• Metastatic breast cancer
• Disease progression on the last chemotherapy regimen received in the metastatic setting
• Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and capecitabine in the neoadjuvant, adjuvant, locally advanced, or metastatic setting and prior treatment with at least two lines of therapy (a line of therapy can be a combination of two agents or single-agent chemotherapy) in the metastatic setting
• At least two lines of anti-HER2 therapy must have been given in the metastatic setting as monotherapy or combined with chemotherapy or hormonal therapy. The HER2-targeted agent can include trastuzumab, lapatinib, or an investigational agent with HER2-inhibitory activity.
• A minimum of 6 weeks of trastuzumab for the treatment of metastatic disease is required
• Patients must have had at least 14 days of exposure in the metastatic setting to lapatinib and capecitabine (given together or separately) unless they were intolerant of lapatinib and/or capecitabine

Exclusion Criteria:

• Chemotherapy ≤ 21 days before enrollment
• Trastuzumab ≤ 21 days before enrollment
• Hormone therapy ≤ 7 days before enrollment
• Granulocyte-stimulating agent < 14 days before enrollment
• Investigational therapy ≤ 28 days before enrollment
• Previous radiotherapy for treatment of metastatic breast cancer ≤ 21 days before enrollment
• Brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 3 months of the first study treatment
• History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins
• History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; Epirubicin > 900 mg/m^2; Mitoxantrone > 120 mg/m^2 and idarubicin > 90 mg/m^2
• Peripheral neuropathy of Grade ≥ 3 per NCI CTCAE, v3.0
• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
• Current unstable angina
• History of symptomatic congestive heart failure (CHF), or ventricular arrhythmia requiring treatment
• History of myocardial infarction within 6 months of enrollment
• LVEF < 50% within 28 days of enrollment
• History of decreased LVEF to < 50% or symptomatic CHF with previous adjuvant trastuzumab treatment
• Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy
• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
• Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment
• Current pregnancy or lactation
• Current known infection with HIV, active hepatitis B, and/or hepatitis C virus
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol