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)