Trial Information

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.