• 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 ]

• Distant metastasis-free survival
• Overall survival
• Pathological response
• Clinical response by RECIST without pathologic response
• Toxicity measured by CTC v2.0

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether chemotherapy is more effective with or without radiation therapy and surgery in treating breast cancer.

PURPOSE: This randomized phase III trial is studying three different regimens of chemotherapy given together with radiation therapy with or without surgery and comparing how well they work in treating women with locally advanced or inflammatory breast cancer.

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.

• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: docetaxel
• Drug: epirubicin hydrochloride
• Drug: fluorouracil
• Procedure: conventional surgery
• Procedure: neoadjuvant therapy
• Radiation: radiation therapy

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

• Swedish Breast Cancer Group
• Swiss Group for Clinical Cancer Research
• Anglo Celtic Cooperative Oncology Group