Paclitaxel, Paclitaxel Albumin-Stabilized Nanoparticle Formulation, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer

Inclusion Criteria:

• Histologically confirmed invasive breast cancer

  • Stage IIIC or IV (locally recurrent or metastatic) disease not amenable to local therapy
• Measurable disease (target lesions), defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension (longest diameter to be recorded) as ≥ 2.0 cm with conventional techniques or as ≥ 1 cm with spiral CT scan

• No non-measurable lesions, including any of the following:

  • Ascites
  • Pleural/pericardial effusion
  • Inflammatory breast disease
  • Lymphangitis cutis/pulmonitis
  • Bone lesions
  • Leptomeningeal disease
  • Cystic lesions
  • Abdominal masses not confirmed and followed by imaging techniques

• HER2/neu status must be known

  • HER2-positive disease allowed provided patient received prior trastuzumab (Herceptin®) or lapatinib (documentation of progression on HER2-directed therapy is not required)

• No progressing or untreated CNS metastases or leptomeningeal disease

  • History of resected brain metastases with stable MRI scans for 3 months, including within the past 4 weeks allowed
  • History of gamma-knife radiosurgery or whole-brain radiation with stable MRI scans for 3 months, including within the past 4 weeks allowed

• Hormone receptor status must be known

  • Estrogen receptor (ER)- and progesterone receptor (PgR)-positive if ≥ 1% cells are positive
• Menopausal status not specified
• ECOG (Zubrod) performance status 0-1
• Life expectancy ≥ 12 weeks
• Granulocytes ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Creatinine ≤ 2.0 mg/dL
• Bilirubin < 1.5 mg/dL (unless due to Gilbert's syndrome)
• AST and ALT ≤ 2.5 times upper limit of normal

• Urine protein ≤ 1+ OR urine protein: creatinine ratio < 1

  • Patients with proteinuria ≥ 2+ at baseline must undergo a 24-hoururine collection that demonstrates < 1 g of protein/24 hr or UPC ratio ≤ 1
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• History of seizures allowed if well controlled with standard medication
• No history of hypersensitivity to paclitaxel or Cremophor® EL CTCAE grade ≥ 3
• No other active malignancy except nonmelanoma skin cancer (patients are not considered to have a "currently active" malignancy if they have completed therapy and are considered by their physician to have less than 30% risk of relapse)
• No history of abdominal fistula or intra-abdominal abscess within 6 months prior to study registration
• No history of gastrointestinal (GI) perforation within the past 12 months
• No history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within the past 6 months
• No history of stroke or transient ischemic attack within the past 6 months

• No history of clinically significant cardiovascular disease including any of the following:

  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mm Hg and/or diastolic BP > 90 mm Hg on antihypertensive medications
  • Prior history of hypersensitivity or hypertensive encephalopathy
  • History of myocardial infarction or unstable angina within past 6 months
  • NYHA congestive heart failure class II-IV
  • Symptomatic peripheral vascular disease
  • Significant vascular disease (e.g., aortic aneurysm or aortic dissection) or arterial thrombotic events
• No serious, non-healing wound, ulcer, or bone fracture
• No significant traumatic injury in the past 28 days
• No peripheral neuropathy ≥ grade 2

• Concurrent full-dose anticoagulants allowed but patient must be on a stable dose of warfarin or low molecular weight heparin

  • Anti-platelet therapy or on daily prophylactic-dose aspirin allowed
  • Stable doses of anticoagulation for atrial fibrillation allowed
• No prior chemotherapy regimen for metastatic disease
• Adjuvant or neoadjuvant taxane allowed provided interval between completion of adjuvant therapy and disease recurrence is ≥ 12 months
• At least 2 weeks since prior radiotherapy

• At least 28 days since prior major surgical procedure or open biopsy and fully recovered

  • There are no restrictions on core biopsies, placement of a vascular access device, or other minor procedures prior to registration.

• At least 7 days since prior hormonal therapy

  • Any number of prior hormonal therapies allowed
• Prior trastuzumab or lapatinib ditosylate for HER2-overexpressing tumors allowed
• Prior bevacizumab allowed
• Prior and concurrent bisphosphonate treatment allowed
• No concurrent major surgical procedure
• No concurrent palliative radiotherapy
• No concurrent aprepitant
• No concurrent pegfilgrastim
• No other concurrent chemotherapy or anticancer hormone therapy