• Disease-free survival by medical history, physical exam, and mammograms every 6 months (annually for mammograms) for 5 years and then annually for 15 years or until death [ Designated as safety issue: No ]
  
• Compare overall survival of patients among the 4 treatment arms by medical history and physical exam every 6 months for 5 years and then annually [ Designated as safety issue: No ]
  
• Compare toxicity among the 4 treatment arms by medical history and physical exam every 6 months for 5 years and then annually [ Designated as safety issue: Yes ]
  

• Compare disease-free survival of patients among the 4 treatment arms by assessment of medical history, physical exam, and mammograms every 6 months (annually for mammograms) for 5 years and then annually for 15 years or until death [ Designated as safety issue: No ]
  
• Compare prognostic biomarkers with outcome and the interaction of these markers with treatment as measured by gene expression analysis before study entry [ Designated as safety issue: No ]
  

OBJECTIVES:

• Compare the disease-free survival of patients with node-positive or high-risk node-negative breast cancer treated with 4 different schedules of adjuvant doxorubicin, cyclophosphamide, and paclitaxel.
• Compare the overall survival of patients treated with these regimens.
• Compare the toxic effects of these regimens in these patients.
• Correlate outcome with putative prognostic markers in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive doxorubicin IV and cyclophosphamide IV on day 1 and pegfilgrastim subcutaneously (SC) on day 2 or filgrastim (G-CSF) SC on days 3-10. Treatment repeats every 14 days for 6 courses.

Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 3 hours on day 1 and pegfilgrastim SC on day 2. Treatment repeats every 14 days for 6 courses.

• Arm II: Patients receive doxorubicin IV on day 1, oral cyclophosphamide on days 1-7, and G-CSF SC on days 2-7. Treatment repeats every 7 days for 15 courses.

Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel and pegfilgrastim as in arm I.

• Arm III: Patients receive doxorubicin, cyclophosphamide, and pegfilgrastim or G-CSF as in arm I.

Beginning 2 weeks after completion of doxorubicin and cyclophosphamide, patients receive paclitaxel IV over 1 hour on day 1. Treatment repeats every 7 days for 12 courses.

• Arm IV: Patients receive doxorubicin, cyclophosphamide, and G-CSF as in arm II. Beginning 2 weeks after completion of cyclophosphamide, patients receive paclitaxel as in arm III.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.

In all arms patients with HER2/neu-positive tumors also receive trastuzumab (Herceptin®) weekly or every 3 weeks beginning concurrently with paclitaxel OR 3 months after the last dose of paclitaxel and continuing for up to 52 weeks.

In all arms, patients with estrogen-receptor or progesterone-receptor positive tumors receive hormonal therapy beginning within 28 days of the completion of adjuvant chemotherapy or radiotherapy (if given).

After finishing study treatment patients are followed once a year for up to 15 years.

PROJECTED ACCRUAL: A total of 4,500 patients (1,125 per treatment arm) will be accrued for this study within 2.25 years.