Inclusion Criteria:

• Patients must have histologically or cytologically confirmed invasive cancer of the breast
• Patients must have documented locally advanced/metastatic disease, defined by the investigator, which is not amenable to resection with curative intent.
• Patients must have HER2-positive breast cancer as defined by ASCO/CAP 2013 guidelines that is confirmed by a Sponsor-designated central laboratory
• Patients must have progressed on, or be intolerant to pertuzumab in the LABC/MBC setting or had disease recurrence within 12 months of pertuzumab treatment in the neoadjuvant or adjuvant setting.
• Patients must have progressed on, or be intolerant to ado-trastuzumab emtansine in the LABC/MBC setting
• Patients must have been previously treated with trastuzumab in any setting (which may have been previously administered with or without pertuzumab)
• ECOG Performance Status of 0 or 1

Exclusion Criteria:

• Patients who have previously been treated with doxorubicin, liposomal doxorubicin, epirubicin, mitoxantrone, or any other anthracycline derivative
• Subjects with central nervous system (CNS) metastases, unless they have been treated and are stable without symptoms for 4 weeks after completion of treatment and must be off steroids for at least 4 weeks prior to enrollment
• Patients with any class of New York Heart Association (NYHA) CHF or heart failure with preserved ejection fraction (HFPEF)
• Patients with a history of known coronary artery disease or a myocardial infarction within the last 12 months
• Patients with a known history of serious cardiac arrhythmias requiring treatment (exception: controlled atrial fibrillation, paroxysmal supraventricular tachycardia)
• Patients who previously discontinued trastuzumab due to unacceptable cardiac toxicity
• Patients with a history of LVEF decline to below 50% during or after prior trastuzumab/lapatinib or other HER2 directed therapy.