Combination Chemotherapy With or Without Trastuzumab in Treating Women With Breast Cancer

OBJECTIVES:

• Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs adjuvant docetaxel and epirubicin, in terms of 5-year survival without relapse, in women with nonmetastatic adenocarcinoma of the breast with lymph node invasion.
• Determine survival of patients treated with these regimens.
• Compare the tolerability of trastuzumab (Herceptin) in patients treated with these regimens.
• Determine the efficacy and tolerability of trastuzumab in patients with hormone receptor-positive tumors.
• Evaluate the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are treated in 2 parts.

• Part I: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive fluorouracil IV, or epirubicin IV, and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy 5 days a week for 5 weeks.
• Arm II: Patients receive epirubicin IV over 10 minutes and docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 6 courses. Patients then undergo radiotherapy as in arm I.

Patients with HER2/neu-positive tumors then proceed to part II. Patients with HER2/neu-negative tumors receive no further treatment.

Patients with hormone (estrogen or progesterone) receptor-positive tumors also receive oral tamoxifen daily beginning after chemotherapy is completed and continuing for 5 years.

• Part II: Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes every 3 weeks for 1 year.
• Arm II: Patients are followed without treatment. Patients not receiving trastuzumab are followed at 4 months, 6 months, every 4 months for 1 year, and then every 6 months for 3 years. Patients receiving trastuzumab are followed at 4 months and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 2,600 patients will be accrued for this study within 3 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed nonmetastatic, unilateral adenocarcinoma of the breast

• Axillary lymph node invasion (N1, N2, or N3)
• No cutaneous invasion
• No T4a or greater disease
• No clinically or radiologically suspected metastases
• No clinically or radiologically suspected contralateral lesion
• No deeply adherent or inflammatory disease
• Complete surgical resection performed, including removal of at least 5 lymph nodes, and with no residual tumor, within the past 42 days
• No prior breast cancer
• Hormone receptor status:

• Not specified

PATIENT CHARACTERISTICS:

Age

• 18 to 64

Sex

• Female

Menopausal status

• Not specified

Performance status

• WHO 0-1

Life expectancy

• Not specified

Hematopoietic

• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• ALT and AST no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• Bilirubin no greater than ULN
• Hepatitis B and hepatitis C negative
• No hepatic dysfunction

Renal

• Creatinine less than 1.3 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Cardiovascular

• ECHO normal
• LVEF at least 50%

Pulmonary

• FEV normal
• No dyspnea at rest
• No supplemental oxygen dependence

Other

• Not pregnant
• Fertile patients must use effective contraception
• HIV negative
• No active infection
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• No contraindication to anthracycline therapy
• No chronic medical or psychological condition
• No geographic or social reason that would preclude study therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy
• No other concurrent chemotherapy
• No contraindication to anthracycline therapy

Endocrine therapy

• No prior hormonal therapy

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Other

• At least 4 weeks since prior experimental therapy