RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Combining combination chemotherapy with hormone therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with or without combination chemotherapy in treating postmenopausal women with stage I or stage II breast cancer that can be surgically removed.

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer stage IIIA breast cancer	Drug: cyclophosphamide  Drug: fluorouracil  Drug: methotrexate  Drug: tamoxifen	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the potential benefits of adjuvant tamoxifen with or without cyclophosphamide, methotrexate, and fluorouracil (CMF) in postmenopausal women with stage I-IIIA, unilateral, invasive breast cancer.

PROTOCOL OUTLINE: This is a randomized study, multicenter study. Patients are stratified according to nodal status (positive vs negative or unknown) and hospital region. Patients undergo surgical resection with or without local radiotherapy, as appropriate. Radiotherapy begins within 8 weeks of surgery for patients randomized to arm I and within 4 weeks after completion of chemotherapy for patients randomized to arm II. Patients are randomized to 1 of 2 treatment arms, preferably within 2 weeks after surgery. Arm I: Beginning within 4 weeks after surgery, patients receive oral tamoxifen daily. Treatment continues for 5 years. Arm II: Beginning within 4 weeks after surgery, patients receive tamoxifen as in arm I and cyclophosphamide IV, methotrexate IV, and fluorouracil IV on day 1 (CMF). Chemotherapy continues every 3 weeks for 6 courses. Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,000 patients will be accrued for this study.

Ages Eligible for Study:  up to  70 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven unilateral, invasive breast cancer; Stage T0-3, N0-1, M0
• No evidence of distant disease, including ipsilateral supraclavicular node enlargement unless proven benign
• No carcinoma in situ alone, including Paget's disease of the nipple without underlying invasion
• No evidence of distant disease, including ipsilateral supraclavicular node enlargement unless proven benign
• No history of pure carcinoma in situ in either breast
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Not specified

--Patient Characteristics--

• Age: 70 and under
• Sex: Female
• Menopausal status: Postmenopausal, defined by 1 of the following criteria: Last menstrual period more than 1 year before initial surgery; Any age with prior bilateral oophorectomy (for nonmalignant reason); Age 50 and over with prior hysterectomy (for nonmalignant reason) without oophorectomy; If at variance with the above definitions, hormonal assays in postmenopausal range take precedence
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: No other serious illness; No other prior invasive malignancy except adequately treated basal cell or squamous cell skin cancer

United Kingdom
      Ayr Hospital, Ayr,  KA6 6DX,  United Kingdom
      Falkirk Royal Infirmary, Falkirk,  FK1 5RE,  United Kingdom
United Kingdom, Scotland
      Aberdeen Royal Infirmary, Aberdeen,  Scotland,  AB25 2ZN,  United Kingdom
      Beatson Oncology Centre, Glasgow,  Scotland,  G11 6NT,  United Kingdom
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom
      Raigmore Hospital, Inverness,  Scotland,  1V2 3UJ,  United Kingdom
      Royal Alexandra Hospital, Paisley,  Scotland,  United Kingdom
      University of Glasgow, Glasgow,  Scotland,  G61 1BD,  United Kingdom
      Western General Hospital, Edinburgh,  Scotland,  EH4 9NQ,  United Kingdom

Study chairs or principal investigators

W.D. George,  Study Chair,  Scottish Cancer Therapy Network   

Study ID Numbers:  CDR0000063696; SCTN-BR9402; EU-94003; UKCCCR-ABC/BR9402
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002581
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08