Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. Monoclonal antibodies including bevacizumab target vascular endothelial growth factor (VEGF) to reduce angiogenesis. We hypothesize that the previously-untested combination of weekly Abraxane® and carboplatin plus biweekly bevacizumab will lengthen time to progression without producing intolerable toxicity.

Anthracycline-based chemotherapy is widely used as adjuvant treatment for breast cancer. In addition to the challenge posed by anthracycline-induced cardiotoxicity, there are issues surrounding previous treatment with anthracyclines which limit its utility in the metastatic disease setting. Many patients with advanced disease will have had prior anthracycline-based adjuvant therapy, may have reached a maximum cumulative lifetime dose, or developed refractory disease, creating an obvious need for non-anthracycline treatment strategies.3 Platinum- and taxane-based chemotherapies as first-line therapy for metastatic breast cancer have demonstrated significant activity, producing single-agent response rates > 50%; in combination these rates increased to > 60% in both previously untreated and in patients who previously received anthracyclines.3 However, overall survival has remained relatively unchanged.4 As there is currently no standard of care for patients with metastatic breast cancer, various physical and psychological factors must be considered when evaluating chemotherapy treatment options, including the patient's tumor biology and growth rate, presence and extent of metastases, history of prior treatment and response, sensitivity and tolerance to therapy, and quality of life.2 Strategies to develop combination, higher dose, or sequential regimens using these active agents, while improving response rates and/or time to progression, may produce increased toxicity without increased survival.2 Because metastatic breast cancer remains essentially incurable using cytotoxic therapy alone, the study of targeted biologics offers new opportunities to enhance drug delivery via their ability to regulate specific receptors that are associated with clinically aggressive disease processes.

Inclusion Criteria:

• Tissue block containing tumor to confirm metastatic breast cancer is required;

• Measurable disease according to RECIST criteria

• "Triple negative" disease defined as tumor demonstrating no expression for estrogen, progesterone or human epidermal growth factor receptor 2(HER2)receptors. "No expression" is categorized as ≤ 10% of cells staining or Allred ≤ 2;

• Aged 18 years or older;

• Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1; life expectancy ≥ 3 months;

• Patients may have received 0 - 1 prior therapies (except taxanes in the metastatic setting). An interval of at least 1 week must have elapsed since prior chemotherapy or hormonal therapy for metastatic disease; at least 6 months must have elapsed since prior adjuvant therapy;

• ≥ 2 weeks between surgery and study enrollment (≥ 4 weeks between major surgery (defined as open abdominal/thoracic/cardiac) and study enrollment;

• Laboratory tests performed within 14 days of study entry:

  • Granulocytes ≥ 1,500/µL;

  • Platelets ≥ 100,000/µL;

  • Hemoglobin ≥ 9 gm/dL;

  • Total bilirubin ≤ institutional upper limit of normal (ULN);

  • Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 5 times ULN;

    • Alkaline phosphatase ≤ 2.5 times ULN;

  • Estimated creatinine clearance ≥ 60 mL/min.

• left ventricular ejection fraction (LVEF)≥ 50% by multigated acquisition (MUGA)/Echocardiogram;

• Informed consent to receive protocol treatment, to provide biologic specimens, and to complete neurotoxicity questionnaires;

• Cognitive and communication skills to comply with study and/or follow-up procedures;

• No reproductive potential:

  • If pre-menopausal: Negative serum pregnancy test and patient agreement to use adequate contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of treatment.
  • If post-menopausal: Amenorrhea for ≥ 12 months.

Exclusion Criteria:

• Pregnant or breast feeding;
• Prior treatment with Abraxane®, carboplatin or bevacizumab, or any taxane for metastatic breast cancer;
• Known hypersensitivity to any component of any study drug;
• Active infection;
• Current neuropathy ≥ grade 2;
• central nervous system (CNS) metastases as determined by head CT with contrast;
• History of bleeding within the past 6 months or active bleeding disorder;
• Serious non-healing wound, ulcer or bone fracture;
• Uncontrolled congestive heart failure (CHF), or history of myocardial infarction(MI), unstable angina, stroke, or transient ischemia within previous 6 months;
• Inadequately controlled hypertension (defined as systolic blood pressure < 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications; prior history of hypertensive crisis or hypertensive encephalopathy;
• Proteinuria (defined as urine protein: creatinine (UPC) ratio ≥ 1.0 or urine dipstick ≥ 2+.
• Significant vascular disease (aortic aneurysm, aortic dissection) or symptomatic peripheral vascular disease;
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within previous 6 months;
• Uncontrolled serious contraindicated medical condition or psychiatric illness.