RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether chemotherapy is effective in treating women who have undergone surgery and radiation therapy for relapsed breast cancer.

PURPOSE: Randomized phase III trial to determine the effectiveness of adjuvant chemotherapy in treating women who have undergone resection for local and/or regional relapsed breast cancer.

Condition	Treatment or Intervention	Phase
recurrent breast cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer stage IIIC breast cancer	Procedure: adjuvant therapy  Procedure: chemotherapy  Procedure: radiation therapy	Phase III

OBJECTIVES: Primary

• Determine the efficacy of adjuvant chemotherapy, in terms of disease-free survival, in women with radically resected loco-regional relapsed breast cancer.

Secondary

• Determine the systemic disease-free and overall survival of patients treated with this regimen.
• Determine the sites of recurrence, incidence of second (non-breast) malignancies, and causes of death without relapse of breast cancer in patients treated with this regimen.
• Determine the quality of life of patients treated with this regimen.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior chemotherapy (yes vs no), estrogen receptor (ER) positive and/or progesterone receptor (PR) positive (yes vs no), and location of recurrence (breast vs mastectomy scar/chest wall vs regional lymph nodes). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive radiotherapy* within 6 months after surgery.
• Arm II: Within 10 weeks after surgery, patients receive at least 3 courses of an adjuvant chemotherapy regimen as determined by the investigator. Patients also receive radiotherapy* within 6 months after surgery and after the completion of chemotherapy OR integrated with chemotherapy. NOTE: *Patients with clear margins (R0) who received prior adjuvant radiotherapy are not required to receive further radiotherapy

Patients with ER and/or PR positive tumors also receive standard hormonal therapy.

Quality of life is assessed at baseline and at 9 and 12 months.

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

PROJECTED ACCRUAL: A total of 978 patients (489 per treatment arm) will be accrued for this study within 4 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed invasive breast cancer
• First local and/or regional (i.e., ipsilateral axillary or internal mammary lymph node region) recurrence after primary treatment with mastectomy or breast-conserving surgery
• No other prior recurrence in any site, including local
• Surgical resection of the recurrence meeting 1 of the following criteria:
• Uninvolved ("clear") margins and planned radiotherapy with at least 50 Gy for patients who had no prior adjuvant radiotherapy
• Microscopically involved margins and planned radiotherapy of at least 50 Gy
• No evidence of distant metastasis, including ipsilateral supraclavicular lymph nodes, by x-ray or CT scan of the chest, ultrasound or CT scan of the abdomen and pelvis, or bone scintigraphy
• No macroscopically incomplete surgery
• No bilateral malignancy except carcinoma in situ
• No suspicious mass in the opposite breast unless that mass has been proven by biopsy to be benign
• No skeletal pain of unknown cause
• No hot spots on bone scan for which metastases cannot be ruled out by x-ray, MRI, and/or CT scan
• Hormone receptor status:
• Determined in the recurrent tumor by immunohistochemistry and/or ligand-binding assay
• Estrogen receptor positive or negative
• Progesterone receptor positive or negative

PATIENT CHARACTERISTICS: Age

• Any age

Sex

• Female

Menopausal status

• Not specified

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No elevated alkaline phosphatase

Renal

• Not specified

Other

• Fertile patients must use effective non-hormonal contraception
• Medically suitable for chemotherapy of 3-6 months duration
• No other primary malignant tumors except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
• No non-malignant systemic disease that would preclude study treatment or prolong follow-up
• No psychiatric or addictive disorder that would preclude giving informed consent
• No history of noncompliance to medical regimens or potential for being unreliable

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

Surgery

• See Disease Characteristics

Switzerland
      Inselspital, Bern, Bern,  CH-3010,  Switzerland; Recruiting

Study chairs or principal investigators

Stefan Aebi, MD,  Inselspital, Bern   

Study ID Numbers:  CDR0000343619; IBCSG-27-02; BIG-1-02; EU-20320
Record last reviewed:  November 2003
Record first received:  December 10, 2003
ClinicalTrials.gov Identifier:  NCT00074152
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05