OBJECTIVES:

• Compare the 5-year and 10-year disease-free survival and overall survival of women with completely resected early stage breast cancer treated with adjuvant paclitaxel, epirubicin, and cyclophosphamide with or without gemcitabine.
• Compare the toxicity, dose-intensity, and tolerability of these regimens in these patients.
• Compare the serious adverse events in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (negative vs 1-3 vs 4 or more), age (50 and under vs over 50), estrogen receptor status (negative vs weakly positive vs positive), concurrent radiotherapy (no vs yes), HER2 status (3+ overexpression vs other vs not measured), and country. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive epirubicin IV, cyclophosphamide IV, and paclitaxel IV over 3 hours on day 1. Patients also receive gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive epirubicin, cyclophosphamide, and paclitaxel as in arm I.

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

PROJECTED ACCRUAL: A total of 3,000 patients (1,500 per treatment arm) will be accrued for this study within 3-4 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed invasive breast cancer

  • Early stage disease

  • Completely resected disease

    • No more than 8 weeks since prior resection
• Any nodal status
• Indication for adjuvant chemotherapy
• No metastatic disease

• Hormone receptor status:

  • Estrogen receptor negative or weakly positive OR
  • Estrogen receptor positive AND progesterone receptor negative or weakly positive

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm3
• Platelet count greater than 100,000/mm3
• Hemoglobin greater than 9 g/dL

Hepatic:

• Bilirubin normal
• AST and ALT no greater than 1.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Other:

• Fit to receive study chemotherapy
• No active uncontrolled infection
• No other malignancy within the past 10 years except basal cell carcinoma or carcinoma in situ of the cervix
• No other concurrent medical or psychiatric problems that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics