Inclusion Criteria:

• Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
• Progression following at least one Herceptin-containing chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
• HER2 positive breast cancer
• Adequate performance status
• Adequate cardiac and liver function
• Adequate blood counts
• Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

Exclusion Criteria:

• More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
• Major surgery, chemotherapy, radiotherapy, investigational agents, or Herceptin within 2 weeks of treatment day 1
• History of inflammatory breast disease
• Active central nervous system metastases (i.e., clinical symptoms, need for corticosteroids, progressive growth)
• Pregnant or breast feeding women
• Gastrointestinal disorder with diarrhea as a major symptom
• Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
• History of life-threatening hypersensitivity to Herceptin