Erlotinib Plus Chemotherapy for Treatment of Triple Negative Breast Cancer

Twenty percent of women with breast cancer have triple negative breast cancer. The standard
treatment for triple negative breast cancer is typically a combination of chemotherapy,
surgery, +/- radiation therapy. When treated with standard therapy women with triple
negative breast cancer have a worse long term outcomes as compared to women who do not have
triple negative breast cancer. Triple negative breast cancer cells usually have a surface
marker called EGFR (epidermal growth factor receptor). Women whose breast cancer cells have
the EGFR surface marker have worse long term outcomes as compared to women whose tumors do
not have the EGFR marker. Erlotinib (Tarceva) targets EGFR and is currently used for
treatment of other cancers like lung and pancreas. This study will assess a combination of
chemotherapy with erlotinib in women with triple negative breast cancer.

For breast cancer patients who receive chemotherapy first and then get surgery, long-term
survival is longer for women who do not have any microscopic cancer at the time of surgery.
The primary objective of this study is to assess whether a combination of chemotherapy and
erlotinib will result in no evidence of microscopic disease (pCR) at the time of surgery in
greater than 20% of enrolled subjects. After completing all chemotherapy, patients will also
receive maintenance erlotinib for 12 months. This is given to study the tolerability of
maintenance Erlotinib and also to evaluate if maintenance erlotinib will decrease the rate
of tumor recurrence.

Inclusion Criteria:

- Female patient ≥ 18 years of age

- Histologically proven stage II or III adenocarcinoma of the breast

- Patients must be candidates for neoadjuvant treatment (tumor size > 2 cm, T2, T3, T4
and/or clinical N1 or N2)

- Estrogen Receptor negative, Progesterone Receptor negative and HER-2 negative disease
(IHC 0 or 1+ and/or FISH negative)

- Performance status of 2 or better

- No prior chemotherapy or endocrine therapy

- If female of childbearing potential, pregnancy test is negative and willing to use
effective contraception while on treatment and for at least 3 months after the last
dose of study drug

- Adequate bone marrow function: neutrophils ≥ 1500/mm3, platelet count ≥ 100,000/mm3,
and hemoglobin ≥ 11 g/dL

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

- Adequate hepatic function: transaminases < 2 x upper limit of normal and total
bilirubin ≤ 1.5 mg/dL

- Patients must have a serum albumin ≥ 3.0 g/dL

- Patients must have a Prothrombin Time, Partial Thromboplastin Time within normal
limits

- Patients 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 within 30 days

- Patients will have a baseline mammogram, bone scan, CT chest and abdomen

Exclusion Criteria:

- Patients with metastatic disease are excluded from study

- 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

- Pregnancy or lactation

- Prior use of an Epidermal growth factor receptor inhibitor

- Patients with a history of chronic pulmonary disease are excluded from study

- 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, with the
exception of adequately treated basal or squamous cell carcinoma of the skin or
carcinoma in situ of the cervix, are excluded from study

- Patients with emotional limitations are excluded from study

- Patients with inflammatory breast cancer will be excluded