OBJECTIVES:

• Compare the effects of synchronous vs sequential adjuvant chemotherapy and radiotherapy on local recurrence, disease-free and overall survival, and treatment delay in women with early-stage breast cancer.
• Compare the safety of these regimens, in terms of dose intensity and toxicity, in this patient population.
• Compare the quality of life and cosmetic outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to clinical oncologist, axillary clearance (yes vs no), radiotherapy boost intent (boost vs no boost), and chemotherapy intent (cyclophosphamide, methotrexate, and fluorouracil [5-FU] vs anthracycline-containing regimen). Patients are randomized to one of two treatment arms.

Patients receive any chemotherapy regimen that includes cyclophosphamide, methotrexate, and 5-FU. Some regimens may also include epirubicin, doxorubicin, mitoxantrone, and/or mitomycin. Chemotherapy repeats every 3 weeks for 4-8 courses.

• Arm I (synchronous chemoradiotherapy): Patients receiving synchronous therapy receive any of the above chemotherapy regimens plus daily radiotherapy between courses 2 and 3 OR courses 5 and 6 of chemotherapy. Radiotherapy is administered for 3-5 weeks.
• Arm II (sequential chemoradiotherapy): Patients receiving sequential therapy receive any of the above chemotherapy regimens followed by daily radiotherapy beginning after completion of all chemotherapy (after course 6 or 8). Radiotherapy is administered for 3-5 weeks.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed before chemotherapy, 2-3 weeks after the completion of all treatment, and then at 1, 2, and 5 years.

Patients are followed annually for 10 years.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 2,250 patients (1,125 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer

  • Early-stage disease

    • No metastatic disease
  • Complete surgical excision of tumor
• Planned use of adjuvant chemotherapy and radiotherapy
• If participating in the cosmetic outcome evaluation portion of the study, must have unilateral disease

• Hormone receptor status

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Bone marrow function adequate

Hepatic:

• Hepatic function adequate

Renal:

• Renal function adequate

Cardiovascular:

• Cardiac function adequate

Other:

• No other prior malignancy except basal cell or squamous cell skin cancer or carcinoma in situ
• No other medical or social condition that would preclude study compliance
• Fit to receive both adjuvant chemotherapy and radiotherapy (administered either synchronously or sequentially)
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• No prior chemotherapy
• No concurrent epirubicin and doxorubicin as a study combination chemotherapy regimen

Endocrine therapy:

• Prior or concurrent hormonal therapy allowed
• No concurrent tamoxifen if treated with methotrexate, mitomycin, and mitoxantrone as a study combination chemotherapy regimen

Radiotherapy:

• See Disease Characteristics
• No concurrent internal mammary chain irradiation
• No concurrent orthovoltage irradiation to the whole breast

Surgery:

• See Disease Characteristics
• Recovered from prior surgery

Other:

• Concurrent participation in another clinical trial allowed