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

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.

- Patients must be women with a histologically confirmed diagnosis of breast cancer that
is more than 1 cm and or lymph node positive

- Physical examination, and scans needed for tumor assessment must be performed within
90 days prior to registration

- Patients with the clinical diagnosis of congestive heart failure or angina pectoris
are NOT eligible

- Serum creatinine within normal limits within 90 days prior to registration

- Bilirubin within normal limits within 90 days prior to registration

- Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate
transaminase (SGPT) =< 2 x the institutional upper limit of normal within 90 days
prior to registration

- Absolute neutrophil count (ANC) of >= 1,500/microliters within 90 days prior to
registration

- Platelet count of >= 100,000/microliters within 90 days prior to registration

- Patients must have a performance status of 0-2 by Zubrod criteria

- Pregnant or nursing women may not participate; women of reproductive potential may not
participate unless they have agreed to use an effective contraceptive method;
pregnancy test required for women of childbearing potential

- In calculating days of tests and measurements, the day a test or measurement is done
is considered day 0; therefore, if a test is done on a Monday, the Monday four weeks
later would be considered day 28; this allows for efficient patient scheduling without
exceeding the guidelines; if day 28 or 42 falls on a weekend or holiday, the limit may
be extended to the next working day

- All patients must be informed of the investigational nature of this study and must
sign and give written informed consent in accordance with institutional and federal
guidelines