Safety Study of AMG 386 to Treat HER2-positive Locally Recurrent or Metastatic Breast Cancer

Inclusion Criteria: * histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease not amenable to any local treatment with curative intent. * HER2-positive by FISH, CISH, or IHC 3+ * ECOG performance status 0 or 1 * Left ventricular ejection fraction greater than or equal to institutional lower limit of normal * Adequate laboratory studies (hematological, chemistries and urinalysis) * Life expectancy greater than or equal to 3 months * Cohort A only: * Trastuzumab naïve or trastuzumab in the neo-adjuvant setting * No clinically significant drop in cardiac function prior exposure to trastuzumab * No prior chemotherapy for metastatic or locally recurrent breast cancer * No prior lapatinib therapy * At least 3 weeks from enrollment since prior chemotherapeutic agents, including taxanes, in the neoadjuvant or adjuvant setting * At least 3 months from enrollment since prior trastuzumab in the neoadjuvant or adjuvant setting * Cohort B only: * Must have failed trastuzumab in the first-line metastatic setting. Trastuzumab must be discontinued for at least 3 weeks prior to enrollment * Must have received prior chemotherapy as adjuvant therapy or for metastatic disease * Prior chemotherapy treatment must be discontinued for at least 3 weeks prior to enrollment * No prior capecitabine * No prior lapatinib Exclusion Criteria: * Inflammatory breast cancer * Central nervous system metastasis * Clinically significant cardiovascular disease * Radiation therapy ≤ 14 days prior to enrollment. * Concurrent anticoagulation therapy, excluding aspirin, anti-platelet agents, low molecular weight heparin or low dose warfarin per protocol. * Uncontrolled hypertension defined as diastolic blood pressure \> 90 mmHg OR systolic blood pressure \> 140 mmHg. * Subjects with a history of prior malignancy, except: * For Cohort B only: * Current or prior history of long QT syndrome * Baseline ECG report of QTc interval of \> 480 milliseconds * Severe chronic liver disease (Child Pugh C)