A Phase I/II Study of HKI-272 in Combination With Trastuzumab (Herceptin) in Subjects With Advanced Breast Cancer

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 cytotoxic chemotherapy
regimen (neoadjuvant, adjuvant, or metastatic setting)

- HER2 positive breast cancer

- At least one measurable target lesion

- Adequate performance status

- Adequate cardiac, kidney, 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, Herceptin or other
cancer therapy within 2 weeks of treatment day 1

- Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2

- Extensive visceral disease

- Active central nervous system metastases

- Pregnant or breast feeding women

- Significant chronic or recent acute gastrointestinal disorder with diarrhea as a
major symptom

- Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)

- Significant cardiac disease or dysfunction

- History of life-threatening hypersensitivity to Herceptin

- Inability or unwillingness to swallow HKI-272 capsules

- Any other cancer within 5 years with the exception of contralateral breast cancer,
adequately treated cervical carcinoma in situ, or adequately treated basal or
squamous cell carcinoma of the skin