Inclusion Criteria:

1. All patients must be female.
2. Signed informed consent.
3. Locally advanced breast cancers or primary breast cancers with concomitant gross metastatic disease are eligible. Locally advanced cancers must be of clinical and/or radiologic size >/- 5 cm, and/or are deemed surgically inoperable, with Stage IIIb, IIIc, or IV disease.
4. HER2 overexpressing tumors defined as HercepTest score of 3+, or >/- 10% cells moderately or strongly HER2 positive by other methods, or semi-quantitative score of >/- 5 (in Dr. Allred's laboratory) or gene amplified.
5. Negative serum pregnancy test (BHCG) within 7 days of starting study, if of child-bearing potential.
6. Kidney and liver function tests - all within 1.5 times the institution's upper limit of normal.
7. Performance status (WHO scale) less than 2 and life expectancy greater than 6 months.
8. Age greater than 18 years.
9. No brain or leptomeningeal disease.
10. No previous or current malignancies at other sites within the last 5 years, with exception of adequately treated core-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.

Exclusion Criteria:

1. Pregnancy or unwillingness to use a reliable contraceptive method in women of child-bearing potential.
2. Severe underlying chronic illness or disease.
3. Cardiomyopathy or baseline LVEF <50%.
4. Other investigational drugs while on study.
5. Severe or uncontrolled hypertension, history of congestive heart failure or severe coronary arterial disease.
6. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded.
7. Taking any GW572016-prohibited medication (see GW572016 Prohibited Medications List in protocol) within 7 days of first dose of study medications.