Phase 2 Trial of Pertuzumab and Trastuzumab With Weekly Paclitaxel and Chemotherapy for HER2 Positive Breast Cancer

Subjects will receive 6 months of T-FEC chemotherapy concomitant with trastuzumab and
pertuzumab before surgery. Subsequently, subjects will undergo surgery to remove any cancer
from the breast and axillary lymph nodes that may have survived the chemotherapy. It is
expected that the majority of women will have no viable cancer left in the breast or lymph
nodes by the time all chemotherapy is completed.

Inclusion Criteria:

- Patients with histologically confirmed stage I-III, HER2-positive invasive breast cancer
for which adjuvant/neoadjuvant chemotherapy is indicated based on physician judgment
following NCCN practice guidelines.

HER2 overexpression or amplification will be based on local test results and is defined as
either:

(i) IHC staining of 3+ (uniform, intense membrane staining) in greater than or equal to 10%
of invasive tumor cells or, (ii) Fluorescent in situ hybridization (FISH) result of more
than six HER2 gene copies per nucleus or, (iii) FISH ratio (HER2 gene signals to chromosome
17 signals) of greater than or equal to 2.0.

- Patients with synchronous bilateral breast cancers are eligible if at least one of the
tumors is HER2-positive.

- Left Ventricular Ejection Fraction (LVEF) greater or equal to 50% at baseline as
determined by either ECHO or MUGA, or within the institution's normal limits.

- Women of childbearing potential must have a negative pregnancy test (serum or urine
beta HCG) prior to initiation of chemotherapy. Both female and male breast cancer
patients who are sexually active have to agree to practice contraception while
participating in the trial and for 3 month after completion of therapy.

- Adequate bone marrow function as indicated by the following:

- ANC greater than or equal to 1500/uL

- Platelets greater than or equal to 100,000/uL

- Hemoglobin greater than or equal to 10 g/dL

- Adequate renal function, as indicated by creatinine less than or equal to 1.5 times
upper limit of normal (ULN)

- Adequate liver function, as indicated by bilirubin less than or equal to 1.5 X ULN and
AST or ALT less than or equal to 2x ULN.

- Signed informed consent.

Exclusion Criteria:

Patients will be excluded from the study based on any of the following criteria:

- Patients who underwent partial excisional biopsy, lumpectomy, segmental mastectomy,
modified radical mastectomy or sentinel node biopsy and, therefore cannot be assessed
for pathologic response accurately.

- Patients who are high risk for developing the following anthracycline, paclitaxel,
trastuzumab or pertuzumab related toxicities including:

History of congestive heart failure, myocardial infarction or cardiomyopathy, uncontrolled
hypertension despite adequate medications Pre-existing peripheral neuropathy > grade 3
Prior anthracycline therapy Known hypersensitivity to any of the study medications Patients
older than age 65 due to increased risk of cardiotoxicity

- Active infection requiring systemic antibiotic therapy.

- Pregnant or lactating women