Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node

Study Overview
=================
Brief Summary
-----------------
The recently randomized trial (ASCOG Z0011) support that among patients with limited sentinel lymph node (SLN) metastatic breast cancer treated with breast conservation and systemic therapy, the use of sentinel lymph node biopsy (SLNB) alone compared with axillary lymph node dissection (ALND) did not result in inferior survival. These patients, therefore, are unlikely to benefit from further surgery that results in a longer period of hospitalization, higher costs and higher postoperative morbidity. This result has been written in the 2012 National Comprehensive Cancer Network Clinical Practice Guidelines. However, Limitations of Z0011, such as failure to achieve target accrual and possible randomization imbalance favoring the SLNB-alone group, must be considered. In the other hand, further testing in different country are needed. The investigators design and begin a prospective randomized multicenter phase III study of ALND vs. no ALND in breast Cancer with positive SLN--the validation of Z0011 in China.

Detailed Description
-----------------
OBJECTIVES: To determine the effects of complete axillary lymph node dissection (ALND) on survival of patients with sentinel lymph node (SLN) metastasis of breast cancer. OUTLINE: This is a randomized multicenter study. Before randomization, all women were stratified according to age (≤50 years, >50 years), tumor size(≤2cm, >2cm) and research center. All the patients underwent lumpectomy and sentinel lymph node biopsy (SLNB). Eligible women were randomly assigned to ALND or no ALND Active Comparator: Patients undergo axillary lymph node dissection involving removal of at least level I and II nodes. Experimental: No surgery of axillary lymph node in this arm. All the patients were to receive whole-breast opposing tangential-field radiation therapy. The use of adjuvant systemic therapy was determined by the treating physician according to the recently NCCN. Patients are followed up every 4 months for the first 2 years, every 6 months from the third year to the fifth year, and then annually for a total of 10 years.

Official Title
-----------------
A Prospective Randomized Multicenter Phase III Study of Axillary Lymph Node Dissection Versus no Dissection in Breast Cancer With Positive Sentinel Lymph Node--the Validation of Z0011 in China

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Procedure: Sentinel Lymph Node Biopsy
* Procedure: Intraoperative Pathological Examination
* Procedure: Axillary Lymph Node Dissection
* Procedure: Pathological Evaluation
* Drug: Adjuvant Systemic Therapy
* Radiation: Radiation Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female; Patient aged 18 years and above; Patient with histological proven invasive breast cancer; Clinical T1-T2 disease with no distant metastasis; Patient with clinical N0 status; Patient for whom conservative surgery with sentinel lymph node (SLN) technique is feasible from the start in terms of carcinologic; Patient with positive SLNs 1 2; Signed consent to participate. Exclusion Criteria: History of neoadjuvant chemotherapy or hormone therapy; History of breast cancer (ipsilateral, i.e. recurrence, or contralateral breast); History of any other invasive cancer; Initial metastatic disease known; Pregnant women or lactating women; Impossibility to undergo medical examinations of the study for geographical, social or psychological reasons.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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: Axillary Lymph Node Dissection<br>After sentinel lymph node biopsy, surgery for standard axillary lymph node dissection. Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician. | Procedure: Sentinel Lymph Node Biopsy<br>* Sentinel lymph nodes are identified with the combining use of intraoperative gamma detector and/or blue dye.<br>* Other names: SLNB;Procedure: Intraoperative Pathological Examination<br>* touch imprint cytology and/or frozen section and/or OSNA<br>Procedure: Axillary Lymph Node Dissection<br>* Axillary lymph node dissection involving removal of at least level I and II nodes.<br>* Other names: ALND;Procedure: Pathological Evaluation<br>* H&E and IHC<br>Drug: Adjuvant Systemic Therapy<br>* Adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.<br>* Other names: chemotherapy or hormone therapy;Radiation: Radiation Therapy<br>* Whole-breast opposing tangential-field radiation therapy.<br>|
| Experimental: Non-Axillary Lymph Node Dissection<br>After sentinel lymph node biopsy, no surgery of axillary lymph node In this study, the absence of surgery is the experimental arm (non-inferiority trial). Pathological evaluation (include intraoperative pathological examination) is performed routinely. All women were to receive whole-breast opposing tangential-field radiation therapy. Adjuvant systemic therapy was determined by the treating physician. | Procedure: Sentinel Lymph Node Biopsy<br>* Sentinel lymph nodes are identified with the combining use of intraoperative gamma detector and/or blue dye.<br>* Other names: SLNB;Procedure: Intraoperative Pathological Examination<br>* touch imprint cytology and/or frozen section and/or OSNA<br>Procedure: Pathological Evaluation<br>* H&E and IHC<br>Drug: Adjuvant Systemic Therapy<br>* Adjuvant systemic therapy was determined by the treating physician according to the recently NCCN.<br>* Other names: chemotherapy or hormone therapy;Radiation: Radiation Therapy<br>* Whole-breast opposing tangential-field radiation therapy.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | Time from randomization to relapse or death. | Time to relapse or progression up to 10 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from randomization to date of death. | Time to death up to 10 years | 
| Axillary Recurrence Rate | Estimate the incidence of axillary recurrence after surgery followed by axillary dissection or after surgery alone. | Time to local relapse up to 10 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast Cancer, Sentinel Lymph Node Biopsy, Axillary Lymph Node Dissection