Study Evaluating HKI-272 (Neratinib) In Subjects With Advanced Breast Cancer

Arm A: HER2 gene amplification and disease progression following at least 6 weeks of standard
doses of Herceptin; Arm B: HER2 gene amplification and no prior Herceptin or HER2-targeted
treatment.

Inclusion Criteria:

- Pathologic diagnosis of breast cancer and current stage IIIB, IIIC, or IV

- Progression following at least 6 weeks of standard doses of Herceptin (Arm A only)

- Over-expression of HER2

- Tumor tissue available and adequate for analysis at screening

- At least one measurable lesion

Exclusion Criteria:

- Prior treatment with Herceptin (Arm B only)

- More than 4 prior cytotoxic chemotherapy regimens

- Subjects with bone or skin as the only site of measurable disease

- Inadequate cardiac function

- Major surgery, chemotherapy, radiotherapy, investigational agents or other cancer
therapy within 1 week of treatment day 1

- Active central nervous system metastases

- Pregnant or breastfeeding women

- Inability to swallow the HKI-272 capsules