I-SPY 2 Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2)

Inclusion Criteria:

- Histologically confirmed invasive cancer of the breast

- Clinically or radiologically measureable disease in the breast after diagnostic
biopsy, defined as longest diameter greater than or equal to 25 mm (2.5cm)

- No prior cytotoxic regimens are allowed for this malignancy. Patients may not have
had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this
malignancy. Prior bis-phosphonate therapy is allowed

- Age ≥18 years

- ECOG performance status 0-1

- Willing to undergo core biopsy of the primary breast lesion to assess baseline
biomarkers

- Non-pregnant and non-lactating

- No ferromagnetic prostheses. Patients who have metallic surgical implants that are
not compatible with an MRI machine are not eligible.

- Ability to understand and willingness to sign a written informed consent (I-SPY TRIAL
Screening Consent)

- Eligible tumors must meet one of the following criteria: Stage II or III, or T4, any
N, M0, including clinical or pathologic inflammatory cancer or Regional Stage IV,
where supraclavicular lymph nodes are the only sites metastasis

- Any tumor ER/PgR status, any HER-2/neu status as measured by local hospital pathology
laboratory and meets any tumor assay profile described in protocol section 4.1.2F

- Normal organ and marrow function: Leukocytes ≥ 3000/μL, Absolute neutrophil count ≥
1500/μL, Platelets ≥ 100,000/μL, Total bilirubin within normal institutional limits,
unless patient has Gilbert's disease, for which bilirubin must be ≤ 2.0 x ULN,
AST(SGOT)/ALT (SGPT) ≤ 1.5 x institutional ULN, creatinine < 1.5 x institutional ULN

- No uncontrolled or severe cardiac disease. Baseline ejection fraction (by nuclear
imaging or echocardiography) must by ≥ 50%

- No clinical or imaging evidence of distant metastases by PA and Lateral CXR,
Radionuclide Bone scan, and LFTs including total bilirubin, ALT, AST, and alkaline
phosphatase

- Tumor assay profile must include on of the following: MammaPrint High, any ER status,
any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, or MammaPrint
Low, ER positive, HER2/neu positive by any one of the three methods used (IHC, FISH,
TargetPrint™)

- Ability to understand and willingness to sign a written informed consent document
(I-SPY 2 TRIAL Consent #2)

Exclusion Criteria:

- Use of any other investigational agents within 30 days of starting study treatment

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to the study agent or accompanying supportive medications.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements