Surgery to Remove Sentinel Lymph Nodes With or Without Removing Lymph Nodes in the Armpit in Treating Women With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Removing the sentinel lymph nodes and examining them under a microscope may help plan more effective surgery for breast cancer. It is not yet known if surgery to remove the sentinel lymph nodes is more effective with or without removal of the lymph nodes in the armpit in treating breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of surgery to remove the sentinel lymph nodes with or without removal of lymph nodes in the armpit in treating women who have breast cancer.

Detailed Description
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OBJECTIVES: Compare the long term control of regional disease by sentinel node resection vs sentinel node resection followed by conventional axillary dissection in women with breast cancer who are clinically node negative and pathologically sentinel node negative. Compare the effect of these two regimens on the overall and disease-free survival of these patients. Compare the morbidity associated with these two regimens in these patients. Compare the prognostic value of these two regimens in patients who are sentinel node negative or positive by pathology. Determine whether a more detailed pathology investigation can identify a group of patients with a potentially increased risk of systemic recurrence who are node negative by pathology. Determine the technical success rate of sentinel node dissection and the variability of technical success rate in a broad population of surgeons. Determine the sensitivity of the sentinel node to determine the presence of nodal metastases in these patients. Objectives of quality of life questionnaire in sentinel node-negative patients: Compare the severity of self-assessed symptoms and activity limitations of patients treated with these two regimens. Compare the severity of self-assessed symptoms and activity limitations after breast cancer surgery in patients whose surgery was on the dominant side vs patients whose surgery was on the non-dominant side. Compare the impact of arm edema, range of motion, and sensory neuropathy on self-assessed measures of daily functioning, symptoms, and overall quality of life of patients treated with these regimens. OUTLINE: This is a randomized study. Patients are stratified according to the surgical treatment plan (lumpectomy vs mastectomy), age (49 and under vs 50 and over), and clinical tumor size (no greater than 2.0 cm vs 2.1-4.0 cm vs at least 4.1 cm). Patients are randomized to one of two surgery arms. All patients receive technetium (Tc 99m) sulfur colloid injected into normal breast tissue within 1 cm of the primary tumor or biopsy cavity and an intradermal injection of technetium (Tc 99m) sulfur colloid, approximately 0.5-8 hours before surgery. Patients also receive an injection of isosulfan blue dye around the tumor or biopsy cavity after a hot spot is identified with a gamma detector. If a hot spot is not identified, the blue dye is injected after a saline bolus injection. Arm I: Patients undergo sentinel node resection immediately followed by conventional axillary dissection. Arm II: Patients undergo sentinel node resection and an intraoperative examination of sentinel nodes. Patients with positive sentinel nodes undergo axillary dissection after sentinel node resection. Patients with cytologically negative sentinel nodes do not undergo axillary dissection. Patients with cytologically negative but histologically positive sentinel nodes return to surgery for axillary dissection. Patients with histologically positive sentinel nodes and those in whom the sentinel node is not identified undergo axillary dissection after sentinel node resection. Patients with pathologically positive, nonaxillary sentinel nodes undergo axillary dissection after sentinel node resection. Patients with evidence of tumor remaining after surgery undergo a total mastectomy. Quality of life is assessed at baseline, at weeks 1-3, and then every 6 months for 3 years or until recurrence. Patients are followed at 1 and 3 weeks, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 5,400 patients will be accrued for this study within 4 years.

Official Title
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A Randomized, Phase III Clinical Trial to Compare Sentinel Node Resection to Conventional Axillary Dissection in Clinically Node-Negative Breast Cancer Patients

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: conventional surgery
* Procedure: Sentinel node resection followed by node examination


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Resectable invasive adenocarcinoma of the breast, confirmed by 1 of the following: Histologically confirmed by core or open biopsy Confirmed by fine needle aspiration cytology AND positive clinical breast examination and ultrasound or mammography Clinically negative lymph nodes No positive ipsilateral axillary lymph nodes No prior removal of ipsilateral axillary lymph nodes No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes, unless proven nonmalignant by biopsy No ulceration, erythema, infiltration of the skin or underlying chest wall (complete fixation), peau d'orange, or skin edema of any magnitude Tethering or dimpling of the skin or nipple inversion allowed No bilateral malignancy or mass in the opposite breast that is suspicious for malignancy, unless proven nonmalignant by biopsy No diffuse tumors or multiple malignant tumors in different quadrants of the breast No other prior breast malignancy except lobular carcinoma in situ No prior or concurrent breast implants Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 years and older Sex: Female Menopausal status: Not specified Performance status: Not specified Life expectancy: At least 10 years (excluding diagnosis of cancer) Hematopoietic: Not specified Hepatic: No hepatic systemic disease Renal: No renal systemic disease Cardiovascular: No cardiovascular systemic disease Other: No prior malignancy within past 5 years except: Effectively treated squamous cell or basal cell skin cancer Surgically treated carcinoma in situ of the cervix Surgically treated lobular carcinoma in situ of the ipsilateral or contralateral breast No concurrent psychiatric or addictive disorder PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for this cancer Chemotherapy: No prior chemotherapy for this cancer, including neoadjuvant chemotherapy Endocrine therapy: No prior hormonal therapy for this cancer Radiotherapy: No prior radiotherapy for this cancer Surgery: See Disease Characteristics No prior breast reduction surgery Prior excisional biopsy or lumpectomy allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I: Conventional axillary dissection<br>Sentinel node resection immediately followed by axillary dissection | Procedure: conventional surgery<br>* Sentinel node resection immediately followed by axillary dissection.<br>|
| Experimental: Arm II: Sentinel node resection followed by node examination<br>Sentinel node resection followed by node examination then axillary dissection if positive sentinel node. | Procedure: Sentinel node resection followed by node examination<br>* Sentinel node resection followed by node examination then axillary dissection if positive sentinel node. No axillary dissection for negative sentinel node.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morbidity - Number of Participants With Residual Shoulder Abduction Deficit | Morbidity as measured by residual shoulder abduction deficit. Shoulder Abduction Deficit definition: Shoulder range of motion decreased by greater than or equal to 10% as compared with that measured prior to surgery. | Before and after surgery (within 30 days of randomization) | 
| Morbidity - Number of Participants With Residual Arm Volume Difference | Morbidity as measured by residual arm volume difference. Residual Arm Volume Difference definition: Arm volume differences greater than or equal to 10% as compared with that measured prior to surgery | before and after surgery (within 30 days of randomization) | 
| Morbidity - Number of Participants With Residual Arm Numbness | Morbidity as measured by residual arm numbness | before and after surgery (within 30 days of randomization) | 
| Morbidity - Number of Participants With Residual Arm Tingling | Morbidity as measured by residual arm tingling | before and after surgery (within 30 days of randomization) | 
| Overall Survival | Measured at the time from randomization to any death to determine the percentage of patients alive at 8 years | 8 years | 
| Disease-free Survival as Measured by Breast Cancer Recurrence, Any Second Primary Cancer, and Death From Any Cause in Patients Without a Prior Event. | Measured at time from randomization to recurrence, second primary, or death to determine the percentage of patients disease free at 8 years. | 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence | Percentage of patients distant disease-free at 5 years. Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery. | From the time of randomization until 5 years | 
| Pathology Investigation of Sentinel Nodes in Sentinel Node Negative Patients to Identify a Group Who Were Potentially at Increased Risk of Systemic Recurrence | Measured at time from randomization to any distant cancer or death to determine percentage of patients distant disease free at 5 years. Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery. | From the time of randomization until 5 years | 
| The Percentage of Technically Successful Sentinel Node Resections as Measured by the Proportion of Patients for Whom at Least One Sentinel Node is Identified. | Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery. | At time of surgery (within 30 days of randomization) | 
| Sensitivity of the Sentinel Node to Determine Presence of Nodal Metastases. | Sentinel node definition: Sentinel nodes are the first few lymph nodes into which a tumor drains. Sentinel node biopsy requires injecting a tracer material to help a surgeon locate sentinel nodes during surgery. | At time of surgery (within 30 days of randomization) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I breast cancer, stage II breast cancer