Evaluate Trastuzumab Plus Standard Chemotherapy Given Before Surgery in Breast Cancer Patients With Low HER 2 Expression
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: nab-paclitaxel; trastuzumab; Doxorubicin; cyclophosphamide; Growth Factor Support; Surgery
Intervention description: 100 MG/M2 IV over 30 minutes once a week for 12 weeks; 4 MG loading dose followed by 2 MG/KG every week for a total of 12 weeks; 60 MG/M2 every two weeks for a total of 4 cycles; 600 MG/M2 every 2 weeks for 4 cycles (administered with Doxorubicin above); All patients will receive pegfilgrastim 6.0 mg sc on Day #2 of each doxorubicin/cyclophosphamide neoadjuvant treatment cycle.
Erythropoetic growth factor support for fatigue/anemia will be allowed at the discretion of the treating physician.; After completion of neoadjuvant therapy, patients will proceed with either modified radical mastectomy or lumpectomy.
All patients with pretreatment lymph node positive disease and positive sentinel lymph node will undergo complete axillary lymph node dissection.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Trastuzumab; Mitogens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: invasive breast cancer; HER2; primary breast cancer; neo-adjuvant therapy; Trastuzumab; Nab-paclitaxel

Summary:

      The purpose of this study is to find out if there is a benefit of adding Herceptin
      (trastuzumab) to standard chemotherapy in this type of breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patient ≥ 18 years of age

          -  Histologically proven stage II or III adenocarcinoma of the breast

          -  Must be candidate for neoadjuvant treatment (Tumor size ≥ 2 cm, T2, T3, T4 and/or
             clinical N1 or N2).

          -  HER-2/neu 1+ or 2+ by immunohistochemistry

          -  Must have operable tumor.

          -  Performance status of 2 or better per SWOG criteria

          -  LVEF ≥ 55% by echocardiogram performed within 4 weeks prior to treatment initiation

          -  If patient of childbearing potential, pregnancy test is negative

          -  Patients with reproductive potential must use an effective method to avoid pregnancy
             for the duration of the trial.

          -  Adequate bone marrow function: ANC > 1500/mm3, platelet count > 100,000/mm3, and
             hemoglobin > 9 g/dL

          -  Adequate kidney function: serum creatinine of < 1.5mg/dl and/or creatinine clearance
             of > 60 mL/min

          -  Adequate hepatic function: transaminases < 2.5 x upper limit of normal and total
             bilirubin < 1.5 mg/dL

          -  Must be informed of the investigational nature of the study and must sign an informed
             consent in accordance with the institutional rules.

          -  Pretreatment lab values must be performed within 14 days of patient registration, and
             other baseline studies (with the exception of mammogram) must be performed within 30
             days of patient registration.

        EXCLUSION CRITERIA:

          -  Patient with metastatic breast cancer.

          -  Women with tumors that are HER-2 neu 0+ or 3+ by immunohistochemistry

          -  Women with HER 2 FISH amplified tumors (FISH ratio >2.2)

          -  Patients who have had prior endocrine therapy for > 4 weeks or chemotherapy for this
             breast cancer will be excluded.

          -  Locally advanced, inoperable tumors will be excluded.

          -  The presence of any other medical or psychiatric disorder that, in the opinion of the
             treating physician, would contraindicate the use of drugs in this protocol or place
             the subject at undue risk for treatment complications.

          -  History of significant cardiac disease, cardiac risk factors or uncontrolled
             arrhythmias

          -  Ejection fraction < 55%

          -  Pregnancy or lactation

          -  Patients with inadequate laboratory values (as defined above) are excluded from study.

          -  Patients with NCI common toxicity criteria (CTC) grade 2 or greater peripheral
             neuropathy are excluded from study.

          -  Patients with active infection are excluded from study.

          -  Patients with concomitant or previous malignancies within the last 5 years, are
             excluded from the study. Exceptions include: adequately treated basal or squamous cell
             carcinoma of the skin, carcinoma in situ of the cervix, and ductal carcinoma in situ
             (DCIS).

          -  Patients with emotional limitations are excluded from study.