RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Chemotherapy uses different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with hormone therapy may kill more tumor cells. It is not yet known which treatment regimen is most effective for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of tamoxifen with that of ovarian ablation, and/or combination chemotherapy in treating premenopausal women with stage I or stage II breast cancer that can be removed by surgery.

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

Further Study Details: 

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

PROTOCOL OUTLINE: This is a randomized, 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 after surgery for patients randomized to arm I or III and within 4 weeks after completion of chemotherapy for patients randomized to arm II or IV. Patients are randomized to 1 of 4 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 in the absence of disease progression or unacceptable toxicity. Arm II: Beginning within 4 weeks after surgery, patients receive tamoxifen as in arm I and cyclophosphamide IV, methotrexate IV, and fluorouracil IV (CMF) on day 1. Chemotherapy continues every 3 weeks for 6 courses. Arm III: Beginning within 4 weeks after surgery, patients receive tamoxifen as in arm I and 1 of 3 ovarian suppression regimens, preferably regimen A. Regimen B is the preferred alternative to regimen A. Regimen A: Patients undergo oophorectomy. Regimen B: Patients undergo radiation-induced menopause comprising radiotherapy to the pelvis on days 1-4. Regimen C: Beginning 4 weeks after surgery, patients receive goserelin subcutaneously (SC) or leuprolide SC or intramuscularly on day 1. Treatment continues every 4 weeks for 2 years. Arm IV: Patients receive tamoxifen as in arm I and CMF as in arm II followed within 4 weeks by ovarian suppression as in arm III. 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 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: Premenopausal, defined by 1 of the following criteria: Last menstrual period less than 1 year before surgery; Under age 50 with prior hysterectomy (for nonmalignant reason) without bilateral oophorectomy; Under age 50 and on continuous oral contraception If at variance with the above definitions, hormonal assays in the premenopausal range take precedence
• Performance status: Not specified
• Life expectancy: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: Not pregnant or nursing; 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, England
      University Hospitals of Leicester, Leicester,  England,  LE1 5WW,  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:  CDR0000063695; SCTN-BR9401; EU-94002; UKCCCR-ABC/BR9401
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002580
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08