RATIONALE: Breast-conserving treatments such as radiation therapy or limited surgery are less invasive than mastectomy and may improve the quality of life. It is not yet known if breast-conserving treatments are as effective as mastectomy followed by radiation therapy in treating locally advanced breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of breast-conserving therapy with mastectomy followed by radiation therapy in treating women who have locally advanced breast cancer that has been previously treated with chemotherapy.

Condition	Treatment or Intervention	Phase
stage II breast cancer stage IIIA breast cancer stage IIIB breast cancer inflammatory breast cancer	Procedure: conventional surgery  Procedure: radiation therapy  Procedure: surgery	Phase III

Further Study Details: 

OBJECTIVES:

• Compare the overall survival and time to loco-regional failure in women with locally advanced breast cancer treated with breast-conserving local therapy vs mastectomy followed by radiotherapy after they have received prior induction chemotherapy.
• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, initial stage (T0, T1, T2, T3, or Tx vs T4), response to prior induction chemotherapy (complete response (CR) vs other), and menopausal status (premenopausal vs postmenopausal). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo mastectomy followed by radiotherapy.
• Patients receive breast-conserving treatment comprising 1 of 3 of the following therapeutic options:
• Regimen A: Patients receive radiotherapy alone.
• Regimen B: Patients with a partial response (PR) to prior induction chemotherapy undergo limited surgery followed by radiotherapy. Patients with a CR to prior induction chemotherapy undergo radiotherapy alone.
• Regimen C: Patients with a partial response (PR) or CR to prior induction chemotherapy undergo radiotherapy alone. Patients with a CR to radiotherapy receive no further treatment. Patients with a PR to radiotherapy undergo limited surgery.

Quality of life is assessed at baseline, at the end of therapy, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Patients are followed within 1 month, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,300 patients (650 per treatment arm) will be accrued for this study within 5 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed locally advanced breast cancer
• T3 inoperable, N0-N2
• Any T, N2
• T4, N0-N2
• Inflammatory breast carcinoma
• Prior treatment with 4-6 courses of standard induction chemotherapy or active investigational regimens completed within the past 4 weeks
• Residual tumor size less than 5 cm
• No fixed axillary lymph nodes
• No multifocal or bilateral breast cancer
• No clinical suspicion of extensive ductal carcinoma in situ
• No unresolved skin edema
• No distant metastases (including ipsilateral supraclavicular node)
• Positive bone scan allowed provided there are no bone metastases on x-ray
• Hormone receptor status:
• Not specified

PATIENT CHARACTERISTICS: Age:

• Any age

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• WHO 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 less than 1.5 times normal
• SGOT and SGPT no greater than 2 times normal
• Alkaline phosphatase no greater than 2 times normal

Renal:

• Creatinine less than 1.5 times normal

Other:

• No other prior or concurrent malignancy except adequately treated squamous cell or basal cell skin cancer or adequately treated cone-biopsied carcinoma in situ of the cervix
• No serious underlying medical illness that would preclude study
• No psychiatric or addictive disorder that would preclude study
• No contraindication to study treatment
• Not pregnant
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• No concurrent hormonal replacement therapy
• No concurrent oral contraceptives

Radiotherapy:

• See Disease Characteristics
• No prior radiotherapy for breast cancer

Surgery:

• No prior surgery for breast cancer other than biopsy for diagnosis confirmation

Other:

• No other prior systemic therapy for breast cancer

Belgium
      Centre Hospitalier Etterbeek Ixelles, Brussels,  B-1050,  Belgium
      U.Z. Gasthuisberg, Leuven,  B-3000,  Belgium
Chile
      Instituto de Radiomedicina, Santiago,  10,  Chile
Israel
      Rambam Medical Center, Haifa,  31096,  Israel
Netherlands
      Akademisch Medisch Centrum, Amsterdam,  1105 AZ,  Netherlands
      Arnhems Radiotherapeutisch Instituut, ARNHEM,  6815 AD,  Netherlands
      Dr. Bernard Verbeeten Instituut, Tilburg,  5042 SB,  Netherlands
      Leiden University Medical Center, Leiden,  2300 CA,  Netherlands
Poland
      Karol Marcinkowski University, Poznan,  60-355,  Poland
      Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw,  02-781,  Poland
      Medical University of Gdansk, Gdansk,  80-211,  Poland
Portugal
      Hospitais da Universidade de Coimbra (HUC), Coimbra,  3049,  Portugal
United Kingdom, England
      Charing Cross Hospital, London,  England,  W6 8RF,  United Kingdom

Study chairs or principal investigators

Jacek Jassem, MD, PhD,  Medical University of Gdansk   
G van Tienhoven, MD, PhD,  Academisch Medisch Centrum   
Marzena Welnicka-Jaskiewicz, MD,  Medical University of Gdansk   
Rodrigo Arriagada, MD,  Instituto de Radiomedicina   
Marie Emson,  Charing Cross Hospital   

Study ID Numbers:  CDR0000069121; EORTC-10974; CEEOG-EORTC-10974; EORTC-22002; GOCCHI-EORTC-10974; ICCG-EORTC-10974; EORTC-BIG-0002; LAMANOMA
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  January 4, 2002
ClinicalTrials.gov Identifier:  NCT00028704
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08