Radiation Therapy in Treating Women With Early-Stage Breast Cancer Who Have Undergone Breast Conservation Surgery

• Location of tumor relapse [ Designated as safety issue: No ]
• Contralateral primary breast cancer or other primary tumors as confirmed by cytological or histological assessment [ Designated as safety issue: No ]
• Regional and distant metastases [ Designated as safety issue: No ]
• Late adverse effects in normal tissues as determined periodically by photographic assessments (in a subset of patients), physician assessments, and patient self-assessments [ Designated as safety issue: Yes ]
• Quality of life as assessed by EORTC QLQ C-30, EORTC QLQ-BR23, BIS, and HADS questionnaires in a subset of patients at baseline, 6 months, and 1, 2, and 5 years [ Designated as safety issue: No ]
• Cost-effectiveness as assessed by EQ-5D questionnaire at baseline, 6 months, and 1, 2, and 5 years [ Designated as safety issue: No ]

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether intensity-modulated radiation therapy is more effective than standard radiation therapy in treating patients with early-stage breast cancer.

PURPOSE: This randomized phase III trial is comparing radiation therapy regimens in treating women with early-stage breast cancer who have undergone breast-conservation surgery.

OBJECTIVES:

• To test partial breast radiotherapy using intensity-modulated techniques following complete local tumor excision in women with low-risk, early stage breast cancer.

OUTLINE: This is a multicenter study.

Patients are stratified according to center (not participating in sub-studies vs participating in sub-studies). Patients are randomized to 1 of 3 treatment arms.

• Arm I (control): Patients undergo standard whole breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks.
• Arm II: Patients undergo reduced whole breast radiotherapy (15 fractions) and standard partial breast radiotherapy (15 fractions) once daily on days 1-5 for 3 weeks.
• Arm III: Patients undergo standard partial breast radiotherapy once daily on days 1-5 (15 fractions) for 3 weeks.

All patients complete a family history questionnaire at baseline. Patients also undergo blood sample collection at baseline and paraffin-embedded tissue collection at follow-up for molecular studies analyzing inter-patient variation by microarrays.

Patients in centers participating in sub-studies undergo quality of life and health economic assessment at baseline, 6 months, and 1, 2, and 5 years. These patients also undergo photographic assessment at baseline, 2 years, and 5 years.

After completion of study treatment, patients are followed for 10 years.

• Active Comparator: Arm I (control)
  Patients undergo standard whole breast radiotherapy once daily on days 1-5 for 3 weeks.
  Intervention: Radiation: radiation therapy
• Experimental: Arm II
  Patients undergo reduced whole breast radiotherapy and standard partial breast radiotherapy once daily on days 1-5 for 3 weeks.
  Intervention: Radiation: radiation therapy
• Experimental: Arm III
  Patients undergo standard partial breast radiotherapy once daily on days 1-5 for 3 weeks.
  Intervention: Radiation: radiation therapy

DISEASE CHARACTERISTICS:

• Diagnosis of low-risk early stage breast cancer, meeting the following criteria:

  • Invasive adenocarcinoma

    • No invasive carcinoma of classical lobular type
    • No lymphovascular invasion
  • Tumor size pathologically determined to be ≤ 3.0 cm in diameter (pT1-2) (< 3.1 cm maximum microscopic diameter of invasive component)
  • Unifocal disease
  • Grade I, II, or III disease

  • Axillary lymph nodes negative (pN0)

    • Sentinel lymph node biopsy and isolated tumor cells < 0.2 mm allowed

• Must have undergone breast conservation surgery with or without adjuvant systemic therapy

  • Minimum microscopic margin of non-cancerous tissue ≥ 2 mm (excluding deep margin if this is at deep fascia)
• At low risk of local recurrence after radiotherapy (< 1% annual risk local recurrence)
• No prior mastectomy
• No blood-borne metastases

PATIENT CHARACTERISTICS:

• No prior malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior endocrine therapy or chemotherapy

  • Neoadjuvant endocrine therapy allowed provided the tumour is < 3.0 cm and all other inclusion criteria are met
  • No primary endocrine therapy as a replacement for surgery
• No concurrent chemoradiotherapy