Trastuzumab and Pertuzumab or Bevacizumab With Combination Chemotherapy in Treating Patients With Stage II-III Breast Cancer

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available for estrogen receptor (ER), progesterone receptor (PR), and HER 2 testing

  • HER2 must be positive by IHC or ISH testing by laboratory standard.
• Needle biopsy or incisional biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Resectable disease-clinical stage I (T/0/N0miT1N0-N0mi), IIA-IIIA (T2 N0/T3N0 or T1-3 N1-N2a) or unresectable disease - clinical stage IIIB/IIIC (T4 or T1-3 N2b-3); no evidence of metastatic disease
• No prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
• Absolute neutrophil count (ANC) ≥1000/ul
• Platelet count ≥ 100,000/ul
• Hemoglobin ≥ 9 g/dl
• Serum creatinine ≤ 1.5 mg/dl or measured creatinine clearance of > 30 ml/min
• Total bilirubin ≤ upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• Patients with multiple foci of invasive cancer in the same breast are eligible if any single lesion meets the above size criteria and all sampled lesions are histologically similar (whether radiographically detected lesions separate from the target lesion are sampled for histologic evaluation is left to the discretion of the treating physicians); the presence of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) in either breast will not render a patient ineligible; patients with a small focus of invasive cancer detected the contralateral breast (clinical T1N0) are eligible, however only the histologic response in the breast containing the target lesions will be considered in determining the patient's pathologic response
• Measurable disease in the breast or axilla that measures at least 1 cm by either clinical or radiographic measurement

Exclusion Criteria:

• Excisional biopsy
• Pregnant and lactating women are not eligible; all participants of reproductive age must have a negative serum pregnancy test at baseline and agree to use an effective barrier method of contraception during the entire period of treatment on the study
• Patients with New York Heart Association (NYHA) grade 2 or higher congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, or arterial thrombotic event with the past 12 months, uncontrolled hypertension (systolic blood pressure > 150 and/or diastolic blood pressure > 100 on antihypertensive medications; patients not on medication for high blood pressure who are found to have systolic blood pressure [SBP] > 150 and/or diastolic blood pressure [DBP] > 100 should have 3 documented episodes of elevated blood pressure before being considered 'uncontrolled', if they have 3 documented episodes of elevated blood pressure, then can be started on antihypertensive medications; patients currently on antihypertensive medications with elevated blood pressures as defined above may have their medications adjusted; if patients have persistent [3 episodes] of high blood pressure despite medication adjustment they will be considered ineligible for study participation; each measured episode should be 24 hours apart), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled or clinically significant arrhythmia, grade II or greater peripheral vascular disease or prior history of stroke or transient ischemic attack (TIA); patient must have a pretreatment multi gated acquisition scan (MUGA) scan or echocardiogram with left ventricular ejection fraction (LVEF) above lower limit of normal
• No non-breast malignancy within the past 5 years other than treated squamous or basal cell carcinoma of the skin or CIS of the cervix
• Patients known to be human immunodeficiency virus (HIV) positive are not eligible for the study given their potentially compromised immune systems and increased risk of treatment-related toxicity
• Advanced (T1N1-4/T2-3 N any) invasive cancer in the contralateral breast
• Any known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage
• Patients must not have a non-healing wound or fracture
• Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
• Patients must not have a bleeding diathesis, hereditary of acquired bleeding disorder or coagulopathy
• Patients on therapeutic doses of Coumadin or Lovenox are ineligible to participate in study
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study; core biopsy or other minor surgical procedure, for example placement of a vascular access device, are excluded from this requirement
• No known hypersensitivity to any component of bevacizumab