OBJECTIVES:

• Compare the disease-free and overall survival of women with completely resected stage I or II breast cancer adjuvantly treated with fluorouracil, epirubicin, and cyclophosphamide (FEC) or epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil (EPI-CMF) versus FEC followed by sequential docetaxel.
• Compare the acute toxicity of these regimens in these patients.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, estrogen receptor status (positive vs negative), and nodal status. Within 8 weeks after definitive surgery, patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients are assigned to 1 of 2 standard adjuvant chemotherapy regimens.

  • Regimen A: Patients receive fluorouracil, epirubicin, and cyclophosphamide (FEC) IV on day 1. Treatment repeats every 3 weeks for 8 courses.
  • Regimen B: Patients receive epirubicin IV on day 1. Treatment repeats every 3 weeks for 4 courses. Patients then receive cyclophosphamide orally on days 1-14 or IV on days 1 and 8 and methotrexate IV and fluorouracil IV on days 1 and 8 (CMF). Treatment with CMF repeats every 4 weeks for 4 courses.
• Arm II: Patients receive 4 courses of adjuvant chemotherapy with FEC as in arm I, regimen A. Patients then receive sequential docetaxel IV over 1 hour once every 3 weeks for 4 courses.

Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are not concurrently enrolled in the Standardization of Breast Radiotherapy (START) trial receive localized radiotherapy once daily, 5 days a week, for 3-5 weeks, according to local practice.

Beginning within 4 weeks after completion of adjuvant chemotherapy, patients who are estrogen receptor and/or progesterone receptor positive receive oral tamoxifen once daily for at least 5 years.

Quality of life is assessed at baseline, before course 5, at 3-4 weeks after course 8, and then at 9, 12, 18, and 24 months after initiation of adjuvant chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 3,340 patients (1,670 per treatment arm) will be accrued for this study within 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed completely resected, invasive breast cancer for which adjuvant chemotherapy is indicated
• No clinical or radiological evidence of locoregional or metastatic disease

• No locally advanced tumors at diagnosis, indicated by any of the following:

  • Fixed tumors
  • Peau d'orange skin changes
  • Skin ulceration
  • Inflammatory changes (T4 or T3b, N2 disease)
• No male breast cancer
• No prior invasive breast cancer or bilateral breast cancer
• Prior ductal carcinoma in situ or lobular carcinoma in situ is allowed
• Must begin study chemotherapy within 8 weeks after definitive surgery

• Hormone receptor status:

  • Estrogen receptor and progesterone receptor status known

PATIENT CHARACTERISTICS:

Age:

• Over 18

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• At least 2 years

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin normal
• AST no greater than 1.5 times normal
• Alkaline phosphatase no greater than 1.5 times normal

Renal:

• Creatinine no greater than 1.5 times normal

Cardiovascular:

• No myocardial infarction within the past 6 months
• No congestive heart failure

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other invasive malignancy within the past 10 years except surgically cured nonmelanoma skin cancer or carcinoma in situ of the cervix
• No other serious medical illness that would limit life expectancy
• No psychiatric condition that would preclude informed consent
• No active uncontrolled bacterial, viral, or fungal infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• See Disease Characteristics
• No prior cytotoxic chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy (e.g., tamoxifen) during study chemotherapy
• No concurrent hormone replacement therapy

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 4 weeks since any prior unlicensed drugs
• No other concurrent experimental drugs