PROTOCOL FOR THE SCOTTISH PREMENOPAUSAL CHEMO-ENDOCRINE TRIAL

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.

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.