I-SPY TRIAL: Neoadjuvant and Personalized Adaptive Novel Agents to Treat Breast Cancer

Inclusion Criteria:

• Histologically confirmed invasive cancer of the breast

• Clinically or radiologically measureable disease in the breast after diagnosticbiopsy, 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 havehad prior chemotherapy or prior radiation therapy to the ipsilateral breast for thismalignancy. 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 baselinebiomarkers

• Non-pregnant and non-lactating

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

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

• Eligible tumors must meet one of the following criteria: Stage II or III, or T4, anyN, 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 hospitalpathology 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 nuclearimaging 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 alkalinephosphatase

• Tumor assay profile must include on of the following: MammaPrint High, any ERstatus, any HER2 status, or MammaPrint Low, ER negative (<5%), any HER2 status, orMammaPrint 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 orbiologic composition to the study agent or accompanying supportive medications.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements