Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression

Neoadjuvant (primary) chemotherapy refers to chemotherapy given before surgery. Neoadjuvant
chemotherapy has a number of potential advantages including increasing the chances for breast
preservation at the time of surgery as well as it may improve the local control of the
cancer. Several national breast cancer studies have shown that neoadjuvant chemotherapy was
equal to chemotherapy given following surgery.

A standard treatment for stage II or Stage III invasive breast cancer with low HER2
expression is combination chemotherapyAdriamycin, Cytoxan,followed by a Taxane: given either
before or after surgery), followed by surgery +/- radiation therapy.

The main purpose of chemotherapy however is to reduce the risk of recurrence of cancer and
also make surgery more successful. HER2 is a receptor located on the surface of some cells.
This receptor plays a role in regulating the growth of the cell, in addition to the growth of
tumors. High levels of the HER2 receptor may predict those women who benefit from treatment
with agents such as Herceptin that target HER2. Herceptin (Trastuzumab) is a drug that is
effective both alone and in combination with standard chemotherapy. There is some data to
suggest that patients whose tumors have low expression of the HER2 protein and are normal by
FISH may also receive benefit from Herceptin.

Inclusion Criteria:

- Female patient ≥ 18 years of age

- Histologically proven stage II or III adenocarcinoma of the breast

- Must be candidate for neoadjuvant treatment (Tumor size ≥ 2 cm, T2, T3, T4 and/or
clinical N1 or N2).

- HER-2/neu 1+ or 2+ by immunohistochemistry

- Must have operable tumor.

- Performance status of 2 or better per SWOG criteria

- LVEF ≥ 55% by echocardiogram performed within 4 weeks prior to treatment initiation

- If patient of childbearing potential, pregnancy test is negative

- Patients with reproductive potential must use an effective method to avoid pregnancy
for the duration of the trial.

- Adequate bone marrow function: ANC > 1500/mm3, platelet count > 100,000/mm3, and
hemoglobin > 9 g/dL

- Adequate kidney function: serum creatinine of < 1.5mg/dl and/or creatinine clearance
of > 60 mL/min

- Adequate hepatic function: transaminases < 2.5 x upper limit of normal and total
bilirubin < 1.5 mg/dL

- Must be informed of the investigational nature of the study and must sign an informed
consent in accordance with the institutional rules.

- Pretreatment lab values must be performed within 14 days of patient registration, and
other baseline studies (with the exception of mammogram) must be performed within 30
days of patient registration.

EXCLUSION CRITERIA:

- Patient with metastatic breast cancer.

- Women with tumors that are HER-2 neu 0+ or 3+ by immunohistochemistry

- Women with HER 2 FISH amplified tumors (FISH ratio >2.2)

- Patients who have had prior endocrine therapy for > 4 weeks or chemotherapy for this
breast cancer will be excluded.

- Locally advanced, inoperable tumors will be excluded.

- The presence of any other medical or psychiatric disorder that, in the opinion of the
treating physician, would contraindicate the use of drugs in this protocol or place
the subject at undue risk for treatment complications.

- History of significant cardiac disease, cardiac risk factors or uncontrolled
arrhythmias

- Ejection fraction < 55%

- Pregnancy or lactation

- Patients with inadequate laboratory values (as defined above) are excluded from study.

- Patients with NCI common toxicity criteria (CTC) grade 2 or greater peripheral
neuropathy are excluded from study.

- Patients with active infection are excluded from study.

- Patients with concomitant or previous malignancies within the last 5 years, are
excluded from the study. Exceptions include: adequately treated basal or squamous cell
carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ
(DCIS).

- Patients with emotional limitations are excluded from study.