Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
Multimodality Treatment for Women With Stage II, Stage III, or Stage IV Breast Cancer
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
 they stop growing or die. Monoclonal antibodies such as trastuzumab can locate tumor cells
 and either kill them or deliver tumor-killing substances to them without harming normal
 cells. Combining chemotherapy, monoclonal antibody therapy, and surgery may be a more
 effective treatment for breast cancer.

 PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy, monoclonal
 antibody therapy, and surgery in treating women who have stage II, stage III, or stage IV
 breast cancer.
OBJECTIVES:

 -  Determine the cardiac and other toxicity of paclitaxel when administered with
 trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB,
 IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.

 -  Determine whether the addition of paclitaxel with or without trastuzumab to conventional
 breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases
 tumor size and the number of positive axillary nodes in these patients.

 -  Determine the 5-year disease-free survival and overall survival of patients treated with
 these regimens.

 -  Determine whether the initial pathologic response in patients receiving neoadjuvant
 therapy correlates with the eventual 5-year disease-free survival or overall survival.

 -  Compare the number of patients eligible for breast-conserving cancer surgery after
 treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.

 -  Correlate clinical and radiographic response rate with pathologic response rate in the
 primary tumor and axillary lymph nodes and determine which parameter best determines the
 pathologic response rate in patients treated with these regimens.

 OUTLINE: Patients either received neoadjuvant therapy (HER-2 overexpressing and
 non-overexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

 -  Neoadjuvant therapy: Patients receive one of two treatment regimens.

 -  Regimen I (HER-2 non-overexpressing patients or HER-2 overexpressing patients who
 refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and
 cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3
 weeks for a total of 4 courses. Patients then undergo surgery with or without
 adjuvant radiotherapy and/or oral tamoxifen.

 -  Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and
 cyclophosphamide as in regimen I. After completion of course 4, patients receive
 paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24.
 Patients then undergo surgery with or without adjuvant radiotherapy. Patients then
 receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not
 receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

 -  Adjuvant therapy: Patients who receive adjuvant therapy (HER-2 overexpressing patients
 only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3
 weeks for a total of 4 courses. After completion of course 4, patients receive
 paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then
 may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks
 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive
 radiotherapy.

 Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
 annually for 5 years.

 PROJECTED ACCRUAL: A total of 125 patients (100 in the neoadjuvant group and 25 in the
 adjuvant group) will be accrued for this study within 5 years.
Inclusion Criteria

 -  Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV
 primary carcinoma of the breast

 -  Fine needle aspiration, core needle biopsy, or incisional biopsy allowed

 -  No excisional biopsy

 -  Any of the following:

 -  Tumor size 2, Nodes 1 (T2N1) or tumor size 3 nodes 0 (T3N0)

 -  Any T with N2 (including axillary lymph nodes matted to one another) or N3

 -  Any T4, including inflammatory breast cancer

 -  Adjuvant patients with at least 4 positive lymph nodes and HER-2
 overexpressing tumor

 -  Supraclavicular or infraclavicular positive lymph nodes without distant
 metastases

 -  Distant metastases with measurable disease in breast or lymph nodes

 -  Synchronous bilateral primary breast cancer allowed if the more serious cancer meets
 entry criteria

 -  Measurable or evaluable disease

 PATIENT CHARACTERISTICS:

 Age: Not specified

 Sex: Female

 Menopausal status: Not specified

 Performance status: Not specified

 Life expectancy: Not specified

 Hematopoietic:

 White cell count > 3000 / mm3 Platelet count > 100,000 / mm3

 Hemoglobin > 9 mg / dl Bilirubin < 1.5 x normal Creatinine < 1.5 x normal left ventricular
 ejection fraction (LVEF) normal by resting nuclear ventriculogram Not pregnant or nursing
 Negative pregnancy test Fertile patients must use effective contraception

 Exclusions

 Prior malignancies except:

 Effectively treated squamous cell or basal cell skin cancer Carcinoma in situ of the cervix
 that has been curatively treated by surgery alone Nonbreast malignancy from which patient
 has been disease-free for 5 years and is at low risk of recurrence