Comparison of Complete Axillary Lymph Node Dissection With Axillary Radiation Therapy in Treating Women With Invasive Breast Cancer (AMAROS)

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase: Completed; Phase 3

Conditions: Breast Cancer

Treatments: Radiation: radiation therapy; Procedure: therapeutic conventional surgery; Procedure: axillary lymph node dissection; Procedure: lymphoscintigraphy

Study type: Interventional

Funder types: NETWORK; Other

Identifiers

NCT00014612

EORTC-10981-22023

Details and patient eligibility

About

RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells and may be a less invasive treatment and cause fewer side effects than complete axillary lymph node dissection. It is not yet known which treatment is more effective for invasive breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of complete axillary lymph node dissection with that of axillary radiation therapy in treating women who have invasive breast cancer.

Full description

OBJECTIVES:

• Compare the regional control of the axilla obtained by complete axillary lymph node dissection vs axillary radiotherapy in sentinel lymph node-positive women with operable invasive breast cancer.
• Determine whether local and regional axillary control can be obtained without axillary lymph node dissection in sentinel lymph node-negative women.
• Compare the axillary 5-year recurrence-free survival of these patients treated with these regimens.
• Compare the morbidity of patients treated with these regimens.
• Compare the quality of life of these patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center and type of breast surgery (conservation vs total mastectomy). Patients are randomized to 1 of 2 treatment arms.

Patients are given an injection of a tracer and undergo lymphoscintigraphy 2-3 hours later to identify the sentinel lymph node. Within 24 hours after lymphoscintigraphy, patients undergo wide local excision of the tumor or mastectomy after the sentinel node is removed. If no sentinel node is found or metastasis is found in a nonsentinel node, patients undergo complete axillary lymph node dissection (ALND) regardless of randomization. Sentinel node-negative patients receive no further treatment. Sentinel node-positive patients continue treatment according to randomization.

• Arm I: Within 8 weeks after surgery, patients undergo complete ALND.
• Arm II: Within 8 weeks after surgery, patients undergo axillary lymph node radiotherapy daily 5 days a week for 5 weeks.

Patients in arm I may receive postoperative axillary irradiation if 4 or more nodes are positive and more than 1 axillary level is involved.

Quality of life is assessed at baseline and then at 1, 2, 3, and 5 years.

Patients are followed annually for 5 years.

PROJECTED ACCRUAL: A total of 3,485 patients (1,394 sentinel node-positive and 2,091 sentinel node-negative) will be accrued for this study within 3 years.

Enrollment: 4,813 patients

Sex: Female

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or "triple diagnosis" (palpation, mammogram or ultrasound, and cytology) confirmed operable invasive breast cancer

  • T0-2, N0
  • Diagnosis by excisional tumorectomy allowed
  • Clinically occult invasive disease must be histologically confirmed

• Only 1 tumor in 1 breast

  • Tumor between 5 and 50 mm in largest diameter, within 1 quadrant by mammogram, ultrasound or MRI

    • Multifocal (i.e., within one quadrant and sharing the same histological characteristics) is allowed
    • Multicentric (i.e., in different quadrants) breast cancer is not allowed

• Clinically negative axillary lymph nodes

• No metastatic disease

• No previous treatment of the primary breast tumor by neoadjuvant hormonal or systemic treatment

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Age:

• Any age

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Fit to undergo sentinel node biopsy, axillary clearance, breast surgery, and/or axillary radiotherapy
• No psychological, familial, sociological, or geographical condition that would preclude study compliance
• No other prior malignancy except basal cell skin cancer or carcinoma in situ of the cervix
• Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to axilla

Surgery:

• No prior surgery to axilla

Other:

• See Disease Characteristics

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4,813 participants in 2 patient groups

axillary lymph node dissection

Active Comparator group

Description:

complete axillary lymph node dissection

Treatment:

Procedure: lymphoscintigraphy

Procedure: axillary lymph node dissection

Procedure: therapeutic conventional surgery

axillary radiotherapy

Experimental group

Description:

axillary radiotherapy, daily for 5 days a week, for 5 weeks

Treatment:

Radiation: radiation therapy

Procedure: lymphoscintigraphy

Procedure: therapeutic conventional surgery