Breast Cancer
Conditions
Keywords
stage IA breast cancer, stage IB breast cancer, stage II breast cancer, estrogen receptor-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-negative breast cancer, progesterone receptor-positive breast cancer
Brief summary
RATIONALE: Surgery to remove lymph nodes in the armpit in patients with sentinel lymph node micrometastases may remove cancer cells that have spread from tumors in the breast. It is not yet known whether surgery to remove the primary tumor is more effective with or without axillary lymph node dissection. PURPOSE: This randomized phase III trial is studying surgery and axillary lymph node dissection to see how well they work compared to surgery alone in treating women with node-negative breast cancer and sentinel lymph node micrometastases.
Detailed description
OBJECTIVES: * Compare disease-free survival of women with clinically node-negative breast cancer with sentinel lymph node micrometastases treated with surgical resection with or without axillary dissection. * Compare overall survival of patients treated with these regimens. * Assess sites of recurrence, particularly reappearance of disease in the undissected axilla. * Assess long-term surgical complications in patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are stratified according to participating center, menopausal status (pre- vs postmenopausal), and preoperative sentinel node biopsy (yes vs no). Patients are followed every 4 months for 1 year, every 6 months for 4 years, and then annually thereafter.
Interventions
PROCEDUREAxillary lymph node dissection
Axillary lymph node dissection
PROCEDURENo axillary lymph node dissection
Therapeutic conventional surgery
Sponsors
ETOP IBCSG Partners Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Clinical, mammographic, ultrasonographic, or pathologic diagnosis of unicentric and unifocal breast carcinoma * Largest tumor lesion ≤ 5 cm * Palpable or nonpalpable breast lesion * Preoperative radioactive occult lesion localization, hook wire, or other method of localization required for nonpalpable lesions * Prior (preoperative) or planned (intraoperative) sentinel node biopsy required * At least 1 micrometastatic (i.e., no greater than 2 mm) sentinel lymph node with no extracapsular extension * No clinical evidence of distant metastases * No suspicious manifestation of metastases that cannot be ruled out by x-ray, MRI, or CT scan, including the following: * Skeletal pain of unknown cause * Elevated alkaline phosphatase * Bone scan showing hot spots * No palpable axillary lymph node(s) * No Paget's disease without invasive cancer * Hormone receptor status: * Estrogen receptor and progesterone receptor known PATIENT CHARACTERISTICS: Age * Any age Sex * Female Menopausal status * Any status Performance status * Not specified Life expectancy * Not specified Hematopoietic * Not specified Hepatic * See Disease Characteristics Renal * Not specified Other * Not pregnant or nursing * No other prior or concurrent malignancy except the following: * Adequately treated basal cell or squamous cell skin cancer * Adequately treated carcinoma in situ of the cervix * Adequately treated in situ melanoma * Contralateral or ipsilateral carcinoma in situ of the breast * No psychiatric, addictive, or other disorder that may compromise ability to give informed consent * Geographically accessible for follow-up PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * See Disease Characteristics Other * No prior systemic therapy for breast cancer * More than 1 year since prior chemopreventive agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 5-year Disease-Free Survival | 5-year estimate reported after a median follow-up of 60 months | Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to first evidence of invasive relapse at any site, second primary tumor (contralateral or non-breast) or death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5-year Overall Survival | 5-year estimate reported after a median follow-up of 60 months | Estimated percentage of patients alive and disease-free at 5 years from randomization, where overall survival is defined as the time from randomization to death of any cause. |
| Site of Recurrence | Reported after a median follow-up of 60 months | Site of recurrence of breast cancer |
Countries
Australia, Belgium, Brazil, Denmark, France, Italy, New Zealand, Peru, Slovenia, Switzerland
Participant flow
Recruitment details
Accrual began April 1, 2001 and closed February 28, 2010, after 934 patients from 27 centers in Europe, South America and Australia were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Axillary Dissection Patients undergo surgical resection of the primary tumor with axillary lymph node dissection following sentinel lymph node assessment.
Axillary lymph node dissection: Axillary lymph node dissection | 464 |
| No Axillary Dissection Patients undergo surgical resection of the primary tumor with no axillary lymph node dissection following sentinel lymph node assessment.
No axillary lymph node dissection: Therapeutic conventional surgery | 467 |
| Total | 931 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Axillary Dissection | No Axillary Dissection | Total |
|---|---|---|---|
| Age, Continuous | 53 years | 54 years | 54 years |
| Sex: Female, Male Female | 464 Participants | 467 Participants | 931 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 178 / 447 | 83 / 453 |
| serious Total, serious adverse events | 1 / 447 | 0 / 453 |
Outcome results
Primary
5-year Disease-Free Survival
Estimated percentage of patients alive and disease-free at 5 years from randomization, where disease-free survival is defined as the time from randomization to first evidence of invasive relapse at any site, second primary tumor (contralateral or non-breast) or death.
Time frame: 5-year estimate reported after a median follow-up of 60 months
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axillary Dissection | 5-year Disease-Free Survival | 84.4 percentage of participants |
| No Axillary Dissection | 5-year Disease-Free Survival | 87.8 percentage of participants |
p-value: 0.00495% CI: [0.55, 1.11]1-sided non-inferiority test
Secondary
5-year Overall Survival
Estimated percentage of patients alive and disease-free at 5 years from randomization, where overall survival is defined as the time from randomization to death of any cause.
Time frame: 5-year estimate reported after a median follow-up of 60 months
Population: Intention-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axillary Dissection | 5-year Overall Survival | 97.6 percentage of participants |
| No Axillary Dissection | 5-year Overall Survival | 97.5 percentage of participants |
p-value: 0.7390% CI: [0.52, 1.54]Log Rank
Secondary
Site of Recurrence
Site of recurrence of breast cancer
Time frame: Reported after a median follow-up of 60 months
Population: Intention-to-treat
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Axillary Dissection | Site of Recurrence | Local recurrence | 10 participants |
| Axillary Dissection | Site of Recurrence | Regional recurrence | 1 participants |
| Axillary Dissection | Site of Recurrence | Contralateral breast cancer | 3 participants |
| Axillary Dissection | Site of Recurrence | Distant recurrence | 34 participants |
| Axillary Dissection | Site of Recurrence | Second (non-breast) primary | 20 participants |
| Axillary Dissection | Site of Recurrence | Death without cancer event | 1 participants |
| No Axillary Dissection | Site of Recurrence | Second (non-breast) primary | 6 participants |
| No Axillary Dissection | Site of Recurrence | Local recurrence | 8 participants |
| No Axillary Dissection | Site of Recurrence | Distant recurrence | 25 participants |
| No Axillary Dissection | Site of Recurrence | Regional recurrence | 5 participants |
| No Axillary Dissection | Site of Recurrence | Death without cancer event | 2 participants |
| No Axillary Dissection | Site of Recurrence | Contralateral breast cancer | 9 participants |