RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen.

PURPOSE: Phase III trial to compare the effectiveness of adjuvant therapy using tamoxifen or ovarian ablation with goserelin or both in treating women with stage I or stage II breast cancer.

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

Further Study Details: 

OBJECTIVES: I. Determine, in a prospective, randomized, controlled trial whether the administration of a course of adjuvant tamoxifen or ablation of ovarian function results in prolongation of time to recurrence or death in patients under 50 years of age with operable carcinoma of the breast.

II. Determine how hormone manipulation affects mood and sexual functioning in these patients.

PROTOCOL OUTLINE: This is a randomized study. Patients are stratified by clinician.

All patients are randomized following primary therapy, which, in addition to surgery, may include local irradiation, perioperative cyclophosphamide, or up to 6 cycles of cyclophosphamide, methotrexate, and fluorouracil (CMF) for high-risk patients. Clinicians may elect to randomize patients to all groups or to only those groups including tamoxifen.

The first group receives no further therapy.

Then second group receives tamoxifen daily for at least 2 years.

The third group receives ovarian ablation with goserelin via monthly injection for at least 2 years.

The final group receives ovarian ablation with goserelin plus daily tamoxifen for at least 2 years.

All patients are followed every 3 months for 2 years, every 6 months for 3 years, then annually.

PROJECTED ACCRUAL: 800 to 1,000 patients will be entered.

Ages Eligible for Study:  up to  49 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Operable, clinical Stage I/II breast cancer (T1-3, N0-1, M0)
• No evidence of distant metastases on x-ray of chest, spine, and pelvis
• Bone scan evidence alone of secondary mass allowed unless considered unequivocal evidence of metastasis
• No primary carcinoma fixed to underlying muscle or chest wall
• No deeply fixed axillary nodes
• No ulceration, skin infiltration, or peau d'orange involving more than 1/3 of breast
• No bilateral tumors
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: Not specified
• Chemotherapy: Chemotherapy for high-risk patients allowed at the discretion of the clinician
• Endocrine therapy: At least 6 weeks since prior hormonal therapy; No concomitant hormonal therapy including oral contraceptives (patients must discontinue the pill for 2 years)
• Radiotherapy: Not specified
• Surgery: Not specified

--Patient Characteristics--

• Age: Under 50
• Sex: Women only
• Menopausal status: Any status
• Performance status: Not specified
• Life expectancy: No limits on life expectancy due to intercurrent illness
• Hematopoietic: WBC at least 3,000; Platelets at least 90,000; Hemoglobin at least 10 g/dL
• Hepatic: Normal liver function required
• Renal: Normal kidney function required
• Other: Fit for surgery; No prior treatment for other malignancies except: Nonmelanomatous skin cancer; Cone-biopsied in situ carcinoma of the cervix; English-speaking patients eligible for quality-of-life assessments

Belgium
      Hopital De Braine-L'Alleud-Waterloo, Braine L' Alleud,  1420,  Belgium
      Institut Jules Bordet, Brussels,  1000,  Belgium
      U.Z. Sint-Rafael, Leuven,  B-3000,  Belgium
United Kingdom, England
      Cancer Research Campaign Clinical Trials Unit-London, London,  England,  SE5 9NU,  United Kingdom
      Castle Hill Hospital, Cottingham,  England,  HU16 5JQ,  United Kingdom
      Clatterbridge Centre for Oncology NHS Trust, MERSEYSIDE,  England,  L63 4JY,  United Kingdom
      Cookridge Hospital, Leeds,  England,  LS16 6QB,  United Kingdom
      Derriford Hospital, Plymouth,  England,  PL6 8DH,  United Kingdom
      Guy's, King's and St. Thomas' Hospitals Trust, London,  England,  SE1 7EH,  United Kingdom
      Huddersfield Royal Infirmary, Huddersfield, West Yorks,  England,  HD3 3EA,  United Kingdom
      Mayday University Hospital, Croydon,  England,  United Kingdom
      Middlesex Hospital- Meyerstein Institute, London,  England,  W1N 8AA,  United Kingdom
      Newcastle General Hospital, Newcastle upon Tyne,  England,  NE4 6BE,  United Kingdom
      North Staffs Royal Infirmary, Stoke on Trent,  England,  ST4 7LN,  United Kingdom
      North Tees General Hospital, Stockton-on-Tees,  England,  TS19 8PE,  United Kingdom
      Portsmouth Hospitals NHS Trust, Portsmouth,  England,  P03 6AD,  United Kingdom
      Radiotherapy Department, Stratford-on-Avon, Warwickshire,  England,  CV37 6NX,  United Kingdom
      Royal Hampshire County Hospital, Winchester,  England,  SO22 5DG,  United Kingdom
      Royal Marsden Hospital, Sutton,  England,  SM2 5PT,  United Kingdom
      Royal Marsden NHS Trust, London,  England,  SW3 6JJ,  United Kingdom
      Royal South Hants Hospital, Southampton,  England,  SO14 0YG,  United Kingdom
      Royal Sussex County Hospital, Brighton,  England,  BN2 5BE,  United Kingdom
      Salisbury General Infirmary, Salisbury,  England,  SP2 7SX,  United Kingdom
      South Tees Acute Hospitals NHS Trust, Middlesbrough, Cleveland,  England,  TS4 3BW,  United Kingdom
      Southampton General Hospital, Southampton,  England,  SO16 6YD,  United Kingdom
      Sunderland Royal Infirmary, Sunderland,  England,  SR2 7JE,  United Kingdom
      Walsgrave Hospital, Coventry,  England,  CV2 2DX,  United Kingdom
      Whittington Hospital, London,  England,  N19 5NF,  United Kingdom
United Kingdom, Northern Ireland
      Ards General Hospital, Newtownards,  Northern Ireland,  United Kingdom
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT8 8JR,  United Kingdom
      Belfast City Hospital Trust, Belfast,  Northern Ireland,  BT9 7AB,  United Kingdom
      Mid-Ulster Hospital, Londonderry,  Northern Ireland,  BT45 5EX,  United Kingdom
United Kingdom, Scotland
      Ninewells Hospital and Medical School, Dundee,  Scotland,  DD1 9SY,  United Kingdom
United Kingdom, Wales
      Velindre Hospital, Cardiff,  Wales,  CF4 7XL,  United Kingdom

Study chairs or principal investigators

Michael Baum,  Study Chair,  Cancer Research Campaign Clinical Trials Centre   

Study ID Numbers:  CDR0000075539; CRC-PHASE-III-88002; UKM-CRC-BR-UNDER 50
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002460
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08