• Progression-free survival [ Designated as safety issue: No ]
  

• Distant metastasis-free survival [ Designated as safety issue: No ]
  
• Overall survival [ Designated as safety issue: No ]
  
• Pathological response [ Designated as safety issue: No ]
  
• Clinical response by RECIST without pathologic response [ Designated as safety issue: No ]
  
• Toxicity measured by CTC v2.0 [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Compare neoadjuvant fluorouracil, epirubicin, and cyclophosphamide vs docetaxel and epirubicin followed by radiotherapy and surgery in women with locally advanced, inflammatory, or large operable breast cancer.
• Compare the progression-free survival of patients treated with these regimens.
• Compare the distant metastasis-free survival and survival of patients treated with these regimens.
• Compare the clinical and pathological responses to these regimens in these patients.
• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to stage of disease (large T2-3 vs locally advanced or inflammatory), p53 status (negative vs positive vs unknown), and participating center. Patients are randomized to 1 of 2 chemotherapy treatment arms.

• Arm I: Patients receive 1 of 3 chemotherapy regimens comprising fluorouracil, epirubicin, and cyclophosphamide (FEC) (according to participating institution).

  • FEC 100: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Canadian FEC: Patients receive oral cyclophosphamide on days 1-14 and epirubicin IV and fluorouracil IV on days 1 and 8. If oral medications are not tolerated, patients may switch to cyclophosphamide IV on days 1 and 8. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
  • Tailored FEC: Patients receive fluorouracil IV over 15 minutes, epirubicin IV over 1 hour, and cyclophosphamide IV over 1-2 hours on day 1. Patients also receive filgrastim (G-CSF) subcutaneously on days 2-15 or until blood counts recover. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive docetaxel IV over 1 hour on days 1, 22, and 43 followed by epirubicin IV over 15 minutes and docetaxel IV over 1 hour on days 64, 85, and 106 in the absence of disease progression or unacceptable toxicity.

Following chemotherapy, patients may undergo loco-regional therapy comprising radiotherapy with or without breast conservation surgery or mastectomy. Patients with estrogen- and/or progesterone-receptor-positive disease also receive tamoxifen or an aromatase inhibitor for 5 years.

Patients are followed every 3 months for 1 year, every 4 months for 1.5 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 1,850 patients will be accrued for this study within 5.5 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Locally advanced or inflammatory disease

    • T4a-d, any N, M0 OR
    • Any T, N2 or N3, M0
    • Large operable T2 or T3 tumors
• No bilateral breast cancer

• Frozen tumor sample available

  • 1 incisional biopsy OR
  • 2 trucut biopsies from a 14G needle

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• 70 and under

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 1.2 mg/dL
• SGOT less than 60 IU/L

Renal:

• Creatinine less than 1.35 mg/dL

Cardiovascular:

• LVEF normal by echocardiography or MUGA

Other:

• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No serious uncontrolled medical condition
• No uncontrolled psychiatric or addictive disorders
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• See Disease Characteristics