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 combination chemotherapy with or without tamoxifen in treating 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. Assess the disease-free and overall survival produced by adjuvant tamoxifen given after postoperative chemotherapy with cyclophosphamide/methotrexate/fluorouracil (CMF) vs. adjuvant CMF alone in women with primary breast cancer.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by age and by participating institution.

All patients undergo surgical resection with local radiation therapy, as appropriate. Within 4 weeks of surgery, patients receive cyclophosphamide, methotrexate, and fluorouracil (CMF) every 3 weeks for 6 courses. Radiotherapy is given within 4 weeks of completion of CMF.

Before beginning the last course of CMF, patients are randomized to receive either oral tamoxifen daily for 5 years or no further therapy.

Patients are followed every 6 months for 5 years, then yearly. Hormone therapy is prohibited except as specified above and except for short-term hormone replacement therapy for severe unresponsive menopausal symptoms.

PROJECTED ACCRUAL: Approximately 2,000 patients will be required. Data on patients entered in Scotland as part of this study will be pooled with data from the EORTC-10901 study.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed breast cancer with palpable, unilateral, invasive disease; Bilateral mammography required within 1 year prior to randomization
• TNM Stage T1-3, N0-1, M0 disease for which adjuvant chemotherapy is considered an essential part of initial therapy; No prior pure in situ carcinoma in either breast; No concurrent in situ carcinoma only; No Paget's disease of the nipple without underlying invasion; No evidence of distant disease, e.g.: No ipsilateral supraclavicular node enlargement unless proven benign
• Hormone receptor status: Any status

--Prior/Concurrent Therapy--

• No prior tamoxifen and not currently receiving tamoxifen

--Patient Characteristics--

• Age: Not specified
• Sex: Women only
• Menopausal status: Pre- or postmenopausal
• Performance status: Not specified
• Hematopoietic: Not specified
• Hepatic: Not specified
• Renal: Not specified
• Other: No serious unrelated illness; No prior invasive malignancy at any other site except adequately treated nonmelanomatous skin cancer; No pregnant or nursing women; Adequate contraception required

United Kingdom
      Ayr Hospital, Ayr,  KA6 6DX,  United Kingdom
      Falkirk Royal Infirmary, Falkirk,  FK1 5RE,  United Kingdom
United Kingdom, England
      Leicester Royal Infirmary NHS Trust, 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:  CDR0000063694; SCTN-BR9403; EU-94004
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002579
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08