Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and candidate for chemotherapy. Patients with measurable and non-measurable disease are eligible (locally recurrent disease must not be amenable to resection with curative intent; patients with de-novo Stage IV disease are eligible)
• HER2-positive metastatic breast cancer (MBC)
• Age ≥ 18 years
• Left Ventricular Ejection Fraction (LVEF) ≥ 50% at baseline (within 42 days of randomization)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of study treatment and for 6 months after the last dose of study treatment
• Signed, written informed consent obtained prior to any study procedure

Exclusion Criteria:

• History of anticancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
• History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
• History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of < 12 months
• History of persistent Grade ≥ 2 hematologic toxicity resulting from previous adjuvant therapy
• Current peripheral neuropathy of NCI-CTCAE, Version 3.0, Grade ≥ 3 at randomization
• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
• Current clinical or radiographic evidence of central nervous system (CNS) metastases
• CT or MRI scan of the brain is mandatory in cases of clinical suspicion of brain metastases
• History of exposure to cumulative doses of anthracyclines
• Current uncontrolled hypertension or unstable angina
• History of CHF of any New York Heart Association (NYHA) criteria, or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months of randomization
• History of LVEF decline to below 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
• Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
• Inadequate organ function within 28 days prior to randomization
• Current severe, uncontrolled systemic disease
• Major surgical procedure or significant traumatic injury within 28 days prior to study treatment start or anticipation of the need for major surgery during the course of study treatment
• Pregnant or lactating women
• History of receiving any investigational treatment within 28 days of randomization
• Current known infection with HIV, HBV, or HCV
• Receipt of IV antibiotics for infection within 14 days of randomization
• Current chronic daily treatment with corticosteroids (excluding inhaled steroids)
• Known hypersensitivity to any of the study drugs
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol