RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is more effective than observation in treating relapsednonmetastatic breast cancer.

PURPOSE: Randomizedphase III trial to compare the effectiveness of combination chemotherapy with that of observation in treating women who have undergone surgery for relapsed nonmetastatic breast cancer.

Condition	Treatment or Intervention	Phase
recurrent breast cancer stage I breast cancer stage II breast cancer stage IIIA breast cancer	Drug: anastrozole  Drug: cyclophosphamide  Drug: docetaxel  Drug: epirubicin  Drug: fluorouracil  Drug: goserelin  Drug: tamoxifen  Procedure: adjuvant therapy  Procedure: antiestrogen therapy  Procedure: aromatase inhibition  Procedure: chemotherapy  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: releasing factor agonist therapy	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the efficacy of adjuvant cyclophosphamide, epirubicin, and fluorouracil vs observation, in terms of disease-free 5-year survival, in women who have undergone resection for relapsed nonmetastatic breast cancer after initial conservative surgery.
• Compare the overall survival of women treated with these regimens.
• Determine the tolerance of these women to the chemotherapy regimen.
• Correlate prognostic factors of survival with efficacy of the chemotherapy regimen in these women.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to menopausal status and participating center. Patients are randomized to 1 of 2 treatment arms. Study begins within 42 days after resection of recurrent disease.

• Arm I: Patients receive fluorouracil IV over 1 hour, epirubicin IV over 1 hour, and cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients are examined on days 1 and 63. Patients who are hormone receptor positive also receive one of the following hormonal therapy regimens, depending on menopausal status:
• Oral tamoxifen daily for 5 years
• Oral tamoxifen daily for 5 years and oral luteinizing hormone-releasing hormone (LHRH) agonist therapy (e.g., goserelin) for 3 years
• Oral LHRH agonist therapy (e.g., goserelin) for 3 years
• Oral antiaromatase therapy (e.g., anastrozole) for 5 years Patients also undergo radiotherapy and may also undergo second complete resection.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 370 patients (185 per treatment arm) will be accrued for this study within 3 years.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the breast
• No contralateral breast cancer
• Local tumor recurrence more than 6 months after conservative surgery
• Complete or conservative resection of the recurrent tumor NOTE: Initial complete surgical resection not allowed
• No local inflammatory disease or disease that is not amenable to complete surgical resection
• No positive axillary lymph nodes
• No distant metastases, including subclavicular lymph nodes
• Hormone receptor status:
• Hormone receptor status known

PATIENT CHARACTERISTICS: Age

• 18 to 65

Sex

• Female

Menopausal status

• Menopausal status known

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Neutrophil count at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin no greater than upper limit of normal (ULN)
• Transaminases no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 2.5 times ULN
• No chronic hepatitis B
• No active hepatitis C

Renal

• Not specified

Cardiovascular

• Cardiac function normal by echocardiogram or isotopes

Other

• No contraindications to anthracyclines such as any of the following:
• Prior doxorubicin over 300 mg/m^2
• Prior epirubicin over 600 mg/m^2
• Prior mitoxantrone over 90 mg/m^2
• No other invasive malignancy
• No chronic somatic or psychiatric condition that would preclude study participation
• No familial, social, geographic, or psychological reason that would preclude study participation
• Not pregnant
• Fertile patients must use effective contraception
• HIV negative
• CA 153 no greater than 2 times ULN

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Patient Characteristics-Other
• No prior neoadjuvant chemotherapy

Endocrine therapy

• No prior neoadjuvant hormonal therapy

Radiotherapy

• No prior neoadjuvant radiotherapy

Surgery

• See Disease Characteristics
• At least 41 days since prior surgery

France
      C.H. Bourg En Bresse, Bourg-en-Bresse,  01012,  France
      C.H. General Andre Boulloche, Montbeliard,  25209,  France
      Centre Eugene Marquis, Rennes,  35042,  France
      Centre Hospitalier Compiegne, Compiegne,  60321,  France
      Centre Hospitalier d'Annecy, Annecy,  74011 Cedex,  France
      Centre Hospitalier de Mulhouse, Mulhouse,  68051,  France
      Centre Hospitalier General, Brive,  19101,  France
      Centre Jean Perrin, Clermont-Ferrand,  63011,  France
      Centre Oscar Lambret, Lille,  59020,  France
      Centre Paul Papin, Angers,  49036,  France
      Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle, Montpellier,  34298,  France
      Centre Regional Francois Baclesse, Caen,  14076,  France
      Centre Regional Rene Gauducheau, Nantes-Saint Herblain,  44805,  France
      CHU Hopital A. Morvan, Brest,  29609,  France
      Clinique Armoricaine De Radiologie, Saint Brieux,  F-22015,  France
      Clinique Claude Bernard, Albi,  81000,  France
      Clinique du Petit Colmouilins, Harfleur,  76700,  France
      Clinique Saint - Pierre, Perpignan,  France
      Hopital J. Ducuing, Toulouse,  France
      Hopital Notre-Dame de Bon Secours, Metz,  57038,  France
      Institut Bergonie, Bordeaux,  33076,  France
      Institut Claudius Regaud, Toulouse,  31052,  France
      Institut Gustave Roussy, Villejuif,  F-94805,  France
      Institut J. Paoli and I. Calmettes, Marseille,  13273,  France
      Institut Sainte Catherine, Avignon,  84082,  France
      Polyclinique de L'Ormeau, Tarbes,  65000,  France

Study chairs or principal investigators

Gilles Romieu, MD,  Study Chair,  Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle   

Study ID Numbers:  CDR0000269549; FRE-FNCLCC-PACS-03/003; EU-20237
Record last reviewed:  February 2005
Last Updated:  February 8, 2005
Record first received:  February 5, 2003
ClinicalTrials.gov Identifier:  NCT00053911
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08