Defining the HER2 Positive (+) Breast Cancer Kinome Response to Trastuzumab, Pertuzumab, Combination Trastuzumab +Pertuzumab, or Combination Trastuzumab + Lapatinib

• Signed, written informed consent
• Age >/= 18 years
• Histologically confirmed HER2+ breast cancer: IHC 3+ or fluorescence in situ hybridization [FISH] amplified; by clinical assay on either primary or metastatic tumor

• Stage I-IV disease

  • For patients with Stage I-IIIc disease:

    1. Scheduled for lumpectomy or mastectomy
    2. No prior or current therapy for breast cancer
    3. Not considered a candidate for therapeutic neoadjuvant treatment

  • For patients with Stage IV disease:

    1. Scheduled for surgical resection of oligometastatic disease
    2. Previously untreated for breast cancer

• Normal relevant end organ function as defined by the following:

  • ANC>1500 cells/mL
  • Platelets > 100,000 cells/mL
  • Hemoglobin > 10 g/dL
  • Total bilirubin ≤ 1.5 x ULN (unless known Gilbert's syndrome)
  • AST and ALT ≤ 2.5 X ULN
  • Creatinine ≤ 1.5 X ULN OR Calculated creatinine clearance ≥50 mL/min OR 24-hour urine creatinine clearance ≥50 mL/min
  • Left Ventricular Ejection Fraction ≥ 50% by ECHO (preferred) or MUGA
• For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner, e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study treatment, and for a minimum of 6 months following trastuzumab and/or pertuzumab administration.
• Sufficient fresh or frozen tissue remaining from pre-treatment core biopsy/ incisional biopsy or willing to undergo biopsy (at UNC via LCCC9819) for research purposes only (approximately 10mg or one core's worth of tissue needed)
• Surgeon and medical oncologist agree one week window trial is appropriate/safe for the patient and that surgery appointment can accommodate treatment schedule as outlined in the study schema (section 4.1).
• UNC patients must co-enroll into LCCC9819 for collection of tissue samples

Exclusion Criteria:

• Pregnant or lactating female
• Prior radiation therapy to the target lesion
• Use of any investigational drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of study medication; a minimum of 10 days between termination of the investigational drug and treatment with study medication is required
• Any major radiotherapy, tumor-directed systemic or immunotherapy within the last 4 weeks for any indication
• Candidate for therapeutic neoadjuvant treatment
• Active infection
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease)
• Required administration of concomitant moderate or strong inhibitors or inducers of CYP3A4 for 14 days prior to the first dose of study drug prior amiodarone for up to 6 months prior to day 1 of study treatment
• Inability to take oral medications e.g., impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral medications (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)

• History or evidence of cardiovascular risk including any of the following:

  • Current uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mmHg) or unstable angina
  • History of serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia)
  • History of myocardial infarction within 6 months of day 1 of dosing
  • History of CHF of New York Heart Association (NYHA) criteria
• Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed)
• Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study drugs
• Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol
• Any other concurrent condition that in the investigator's opinion would jeopardize compliance with the protocol