A Comparison of Intensive Sequential Chemotherapy Using Doxorubicin Plus Paclitaxel Plus Cyclophosphamide With High Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Support for Primary Breast Cancer in Women With 4-9 Involved Axillary Lymph Nodes

OBJECTIVES: I. Compare disease free survival and overall survival in women with operable breast cancer and at least 4 positive axillary lymph nodes treated with intensive sequential chemotherapy with doxorubicin, paclitaxel, and cyclophosphamide versus standard dose doxorubicin and cyclophosphamide followed by high dose STAMP I (cyclophosphamide, cisplatin, and carmustine) or STAMP V (cyclophosphamide, carboplatin, and thiotepa) and autologous stem cell rescue. II. Compare the toxic effects of these regimens in this patient population. III. Measure the breast cancer cell content of the peripheral blood progenitor cell (PBPC) fractions from patients randomized to the PBPC supported arm and correlate the results with the disease free survival, survival, and pattern of relapse in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by center, primary treatment (mastectomy alone vs mastectomy plus radiotherapy following chemotherapy vs breast conserving surgery plus radiotherapy following chemotherapy), menopausal status (premenopausal vs postmenopausal), estrogen and/or progesterone receptor status (positive vs negative vs unknown), N2 disease (yes vs no), T3 disease (yes vs no), myeloablative chemotherapy regimen (STAMP I vs STAMP V), and source of progenitor cells (marrow vs peripheral blood vs both). Patients are randomized to 1 of 2 treatment arms: Arm I: Patients receive doxorubicin IV over 1 hour on days 1, 15, and 29, paclitaxel IV over 24 hours on days 43, 57, and 71, and cyclophosphamide IV over 1 hour on days 85, 99, and 113. Patients receive filgrastim (G-CSF) subcutaneously on days 3-10, 17-24, 31-38, 45-52, 59-66, 73-80, 87-94, 101-108, and 115-122. Arm II: Mobilization chemotherapy: Patients receive doxorubicin IV over 1 hour and cyclophosphamide IV over 1 hour on days 1, 22, 43, and 64. Harvest: Patients undergo harvest of autologous bone marrow and/or peripheral blood stem cells (PBSC). Patients who undergo harvest of PBSC alone do not receive mobilization chemotherapy but receive hematopoietic growth factors prior to harvest. High dose myeloablative chemotherapy: Patients receive STAMP I OR STAMP V: STAMP I: Patients receive cyclophosphamide IV over 1 hour and cisplatin IV over 24 hours on days -6 to -4 and carmustine IV over 2 hour on day -3. STAMP V: Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4. Transplantation: Autologous bone marrow and/or PBSC are reinfused on day 0. Both arms: Patients who are postmenopausal or who have hormone receptor positive disease receive oral tamoxifen daily beginning 4 weeks after the completion of chemotherapy and continuing for 5 years. Patients who underwent breast conserving surgery receive locoregional radiotherapy 5 days a week for 4.5-5.5 weeks beginning 4-6 weeks after the completion of chemotherapy. Patients who underwent modified radical mastectomy may receive locoregional radiotherapy 5 days a week for 5 weeks at the discretion of their physician. Patients are followed every 4 months for 3 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients (500 per arm) will be accrued for this study within 5 years.