INST 0514C- A Neoadjuvant Phase II Trial of GW572016 in HER2 Overexpressing Breast Cancer Patients: Biologic Correlative Study

Inclusion Criteria:

1. All patients must be female.

2. Signed informed consent.

3. Only subjects with Stage IIIa, IIIb, IIIc, or IV disease should be enrolled in this
trial. Locally advanced breast cancers of clinical and or radiologic size greater
than or equal to 3 cm, or primary breast cancers with concomitant gross metastatic
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 (beta-HCG) 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) <2 and life expectancy >6 months.

8. Age >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 cone-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