Inclusion Criteria:

- Histologically or cytologically confirmed HER2-overexpressing breast cancer

- Prior or newly documented HER2 amplification by fluorescence in situ hybridization
(FISH)

- Progressive metastatic disease

- Must have received at least one prior chemotherapy regimen for metastatic breast
cancer

- At least 1 measurable or evaluable lesion

- At least 1 lesion accessible for 2 separate core biopsies for pharmacodynamic
evaluation

- 18 and over

- Male or female

- ECOG 0-1

- Life expectancy, More than 3 months

- Hematopoietic

- Absolute neutrophil count at least 1,500/mm^3*

- Platelet count at least 100,000/mm^3* NOTE: *Without hematopoietic growth
factors or transfusions

- Hepatic

- Bilirubin no greater than 1.5 mg/dL

- AST/ALT no greater than 2.5 times upper limit of normal (ULN) (5 times ULN if
liver metastases are present)

- Renal

- Creatinine no greater than 1.5 times ULN OR

- Creatinine clearance at least 60 mL/min

- Cardiovascular

- 12-lead ECG with normal tracing

- history of cardiovascular disease (i.e., ischemic heart disease, arrhythmia, or
congestive heart failure) unless asymptomatic for the past year with no requirement
for antiarrhythmics or a clinically significant medical management change

- Gastrointestinal

- Able to take oral medication* Negative pregnancy test

- Fertile patients must use effective contraception

- At least 4 weeks since prior trastuzumab (Herceptin)

- At least 4 weeks since other prior biologic therapy or immunotherapy

- At least 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas)

- At least 6 months since prior doxorubicin or doxorubicin equivalents without any
prior or developing signs or symptoms of cardiomyopathy

- No cumulative doses of more than 300 mg/m^2

- At least 2 weeks since prior hormonal therapy for the primary disease

- Concurrent hormone replacement therapy or luteinizing hormone-releasing hormone
agonists allowed

- At least 4 weeks since prior radiotherapy

- At least 3 weeks since prior major surgery (2 weeks for minor surgery)

- Recovered from prior therapy

- At least 4 weeks since prior investigational treatment

- Coumarin or heparin derivatives allowed for the prevention of deep vein thrombosis or
port patency

Exclusion Criteria:

- known or clinically suspected brain metastases or leptomeningeal disease

- symptomatic edema or third-space fluid (e.g., ascites or pleural effusions)

- known hepatitis B or C infection

- significant ECG changes that require medical intervention

- QTc interval less than 460 msec

- No history of torsade or other symptomatic QTc abnormality

- LVEF greater than 50% by MUGA

- gastrointestinal abnormality that would require medications (including all antacids)

- persistent symptoms of an esophageal or digestive disorder

- pregnant or nursing

- known HIV infection

- active infection

- concurrent uncontrolled systemic disorders or laboratory abnormalities that would
preclude study drug safety evaluation

- mental disorder that would preclude study compliance or ability to give informed
consent

- No more than 2 prior trastuzumab-based regimens for advanced disease

- concurrent immunotherapy

- more than 1 prior anthracycline- or anthracenedione-containing regimen (except with
approval of the sponsor)

- prior high-dose chemotherapy with hematopoietic stem cell transplantation

- concurrent anticancer chemotherapy

- No concurrent anticancer hormonal therapy, including tamoxifen

- prior radiotherapy to the only disease site that would be assessed for response

- concurrent radiotherapy

- prior partial or complete gastrectomy

- concurrent antiarrhythmics

- concurrent antacids

- concurrent anticoagulant at therapeutic doses

- other concurrent experimental anticancer medications for breast cancer