Neoadjuvant Dose-Dense For Early Her2Neu Positive Breast Cancer

Inclusion Criteria:

The patient must have signed and dated an IRB-approved consent form that conforms to
federal and institutional guidelines.

- Female

- 18 years or older

- ECOG performance status of 0 or 1

- Eligible tumors must meet one of the following criteria:

- Operable (T1c, T2-3, N0-1, M0)

- Locally advanced (T2-3, N2-3, M0 or T4a-c, any N, M0)

- Inflammatory breast cancer (T4d, any N, M0)

- Staging evaluation:

- History and physical exam, cbc, chemistry profile

- CT Chest/Abdomen/Pelvis and a bone scan or PET/CT as needed

- Diagnosis of invasive adenocarcinoma made by core needle biopsy

- Breast cancer determined to be:

- Confirmed HER2-positive : (ASCO CAP guidelines, 10/7/2013)

- IHC 3+ based on circumferential membrane staining that is complete, intense

- ISH positive based on:

- Single probe average HER2 copy number ≥ 6 signals/cell

- Dual probe HER2/CEP 17 ratio ≥ 2.0 with an average HER2 copy number ≥ 4.0
signals/cell

- Dual probe HER2/CEP 17 ratio ≥ 2.0, with an average HER2 copy number of < 4.0
signals/cell

- Dual probe HER2/CEP 17 ratio < 2.0 with the average HER2 copy number of ≥ 6.0
signals/cell

- any ER or PR receptor status

- LVEF assessment by echocardiogram within 30 days of initiation; EF of ≥ 55% considered
normal.

- Normal troponin I level at baseline

- Blood counts must meet the following criteria:

- ANC greater than or equal to 1500/mm3

- Platelet count greater than or equal to 100,000/mm3

- Hemoglobin greater than or equal to 10 g/dL

- Serum creatinine less than or equal 2.5 mg/100ml

- Adequate hepatic function by these criteria: total bilirubin must be less than or
equal to 1.5 x the ULN for the lab unless the patient has a bilirubin elevation great
than the ULN to 1.5 x ULN due to Gilbert's disease or similar syndrome involving slow
conjugation of bilirubin; and alkaline phosphatase must be less than or equal to 2.5 x
ULN for the lab; and AST must be less than or equal to 1.5 x ULN for the lab. Both
alkaline phosphatase and AST may not both be greater than the ULN.

- Patients with AST or alkaline phosphatase > ULN are eligible for inclusion in the
study if liver imaging (CT, MRI, PET-CT or PET scan) performed within 90 days prior to
randomization does not demonstrate metastatic disease and the requirements are met as
above

- Patients with alkaline phosphatase that is > ULN but less than or equal to 2.5 x ULN
or unexplained bone pain are eligible for inclusion in the study if a bone scan,
PET-CT scan, or PET scan performed within 90 days prior to randomization does not
demonstrate metastatic disease.

Exclusion Criteria:

Patients with a history of decompensated congestive heart failure or an EF < 55% will be
excluded

• Cardiac disease that would preclude the use of the drugs included in the above regimens.
This includes but is not confined to:

- Active cardiac disease:

- angina pectoris requiring the use of anti-anginal medication;

- ventricular arrhythmias except for benign premature ventricular contractions
controlled by medication;

- conduction abnormality requiring a pacemaker;

- supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with
medication; and

- clinically significant valvular disease

- symptomatic pericarditis

- pulmonary hypertension

- History of cardiac disease:

- myocardial infarction;

- congestive heart failure; or

- cardiomyopathy