Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery
Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery
RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide,
 and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop
 the growth of tumor cells, either by killing the cells or by stopping them from dividing.
 Colony-stimulating factors, such as filgrastim, may increase the number of immune cells found
 in bone marrow or peripheral blood and may help the immune system recover from the side
 effects of chemotherapy. Monoclonal antibodies, such as trastuzumab, can block tumor growth
 in different ways. Some block the ability of tumor cells to grow and spread. Others find
 tumor cells and help kill them or carry tumor-killing substances to them. Giving combination
 chemotherapy and filgrastim together with trastuzumab may kill more tumor cells.

 PURPOSE: This phase II trial is studying how well giving doxorubicin hydrochloride,
 cyclophosphamide, and filgrastim together followed by paclitaxel albumin-stabilized
 nanoparticle formulation and trastuzumab works in treating patients with breast cancer
 previously treated with surgery
PRIMARY OBJECTIVES:

 I. To assess disease-free survival following a dose-intensive weekly regimen of Adriamycin +
 oral cyclophosphamide augmented with G-CSF support followed by Abraxane and Herceptin if
 appropriate for adjuvant treatment of high risk breast cancer patients.

 SECONDARY OBJECTIVES:

 I. To assess the toxicity associated with this regimen. II. To assess the delivered dose
 intensity of the regimen. III. To assess time to treatment failure and overall survival of
 the regimen. IV. To assess the incidence and severity of delayed nausea and vomiting with
 this regimen.

 OUTLINE:

 Patients receive dose-intensive chemotherapy comprising doxorubicin hydrochloride IV over
 10-15 minutes on day 1, oral cyclophosphamide once daily on days 1-7, and filgrastim
 subcutaneously on days 2-7. Courses repeat every 7 days for up to 12 weeks in the absence of
 disease progression or unacceptable toxicity. Beginning 1 week later, patients then receive
 paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once a week for 12
 weeks in the absence of disease progression or unacceptable toxicity. Patients with HER-2/neu
 positive disease also receive trastuzumab IV over 30-90 minutes once a week for 1 year in the
 absence of disease progression or unacceptable toxicity.

 After completion of study treatment, patients are followed up every 3 months for 2 years,
 every 6 months for 2 years, and then annually thereafter.
Inclusion Criteria:

 -  Have a histologically confirmed diagnosis of primary breast carcinoma that has been
 surgically resected; (this regimen is not intended for neoadjuvant treatment)

 -  4 + nodes

 -  OR if 1-3 + nodes, either ER OR HER-2/neu+

 -  OR have high-risk node negative disease that is HER-2/neu positive OR >= 2.0 cm tumor
 size

 -  HER-2/new + definition: patient has known tumor HER-2/new expression = 3+ by IHC or,
 if 2+ by IHC confirmed to be FISH positive

 -  Patients with clinically apparent cardiac disease, or history of same, are not
 eligible; patients who are >= 60 years of age or who have a history of hypertension
 must have an echocardiogram or MUGA prior to enrollment; patients with breast cancer
 that is HER-2/neu positive and a treatment plan that includes Herceptin must have an
 echocardiogram or MUGA scan prior to enrollment; the LVEF must be within the
 institutional normal range; if LVEF is > 75%, the investigator should consider having
 the LVEF reviewed or repeating the MUGA prior to registration

 -  WBC >= 4,000

 -  ANC >= 1,500

 -  Platelet count >= 100,000

 -  Serum creatinine =< 1.5 x IULN

 -  Bilirubin =< 2.0

 -  SGOT/SGPT/alkaline phosphatase =< 2 x IULN

 -  Elevations greater than these require metastatic work up

 -  Be informed of the investigational nature of this study and provide written informed
 consent in accordance with institutional and federal guidelines prior to study
 specific screening procedures

 Exclusion Criteria:

 -  Except for the following, no other malignancy is allowed: synchronous ipsilateral
 breast cancer of the same subtype (ER/PR, HER-2/neu), adequately treated basal cell or
 squamous cell skin cancer, in situcervical cancer or other stage I or II cancer from
 which the patient has been disease free for at least 5 years

 -  Patients with cardiac disease that would preclude the use of Adriamycin, Taxol or
 Herceptin are not eligible; this includes:

 -  Angina pectoris that requires the use of antianginal medication

 -  Cardiac arrhythmia requiring medication

 -  Severe conduction abnormality

 -  Clinically significant valvular disease

 -  Cardiomegaly on chest x-ray

 -  Ventricular hypertrophy on EKG

 -  Uncontrolled hypertension, (diastolic greater than 100 mm/Hg or systolic > 200 mm/hg)

 -  Current use of digitalis or beta blockers for CHF

 -  Clinically significant pericardial effusion

 -  Myocardial infarction documented as a clinical diagnosis or by EKG or any other test

 -  Documented congestive heart failure

 -  Documented cardiomyopathy

 -  Documented arrhythmia or cardiac valvular disease that requires medication or is
 medically significant

 -  Patients who have received prior chemotherapy or radiotherapy are not eligible

 -  Patients who are pregnant or breastfeeding are not eligible; women of child bearing
 potential must agree to practice adequate contraception

 -  Patients with active infection are not eligible

 -  Patients who are known to be infected with HIV, hepatitis B or hepatitis C are not
 eligible; testing is not required unless there is a high index of clinical suspicion

 -  Patients suffering from psychiatric impairment are not eligible