Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting

• Progression free survival [ Time Frame: 2 years ]
  Progression is defined as a new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by ultrasound (U/S) or MRI. Analyzed using the Kaplan-Meier method. Cox proportional-hazards analysis will be used to derive the hazard ratio and 95% confidence interval between the two treatment arms, adjusted for clinical and demographic variables.
  
  

• Clinical complete response in the neoadjuvant setting [ Time Frame: Up to 5 years ]
  Defined as normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange. The 95% confidence interval (CI) will be computed.
  
  
• Microscopic pCR in the neoadjuvant setting [ Time Frame: Up to 5 years ]
  Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed.
  
  
• Toxicity of the combinations in HER2 positive and HER2 negative breast cancer assessed using the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 [ Time Frame: Up to 5 years ]
  The frequency of toxicities will be recorded.
  
  

PRIMARY OBJECTIVES:

I. To estimate 2 year progression-free survival in patients with breast cancer more than 1 cm and/or lymph node positive breast cancer treated with weekly Carboplatin/Nab-Paclitaxel (with trastuzumab in patients with HER2+ disease, and with bevacizumab in HER2-).

II. To measure clinical response rates in patients treated in the neoadjuvant setting.

III. To measure the microscopic pathological response rate of this regimen in patients treated in the neoadjuvant setting.

IV. To measure the toxicity and delivered dose intensity of this regimen. V. To assess the association between microscopic pathologic complete response and clinical complete response at the primary tumor site in these patients.

VI. To measure the outcome of patients treated with doxorubicin and cyclophosphamide with patients not treated with doxorubicin and cyclophosphamide.

SECONDARY OBJECTIVES:

I. Develop quantitative analysis methods to obtain pre-treatment tumor characteristic morphological, enhancement kinetic, and Choline metabolic parameters in breast cancer. Select an optimal set of features using the logistic regression analysis and the Artificial Neural Network (ANN) to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.

II. Investigate whether the early response patterns, analyzed using the percent tumor size changes, or changes in other lesion characteristic parameters, can be used to predict pathologic complete remission (pCR) in HER-2 positive and negative arm.

III. Investigate whether combining the pre-treatment tumor characteristic parameters, and the early response pattern during the treatment course, can achieve a higher "area under the receiver operating characteristic (ROC) curve" (AUC) in prediction of pCR than those based on pre-treatment MRI characteristics or tumor response patterns alone.

OUTLINE: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes and carboplatin IV over 60 minutes once weekly for 12 weeks. Patients with HER2-positive disease receive trastuzumab IV over 30-90 minutes once weekly for 12 weeks and patients with HER2-negative disease receive bevacizumab IV over 30-90 minutes once every two weeks for 5 doses. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 21-40 days later, patients undergo surgery.

After completion of study treatment, patients are followed for 5 years.