Targeted Axillary Dissection (TAD) in Early-stage Node Positive Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: It is now standard for most breast cancer patients with 1-2 positive sentinel nodes to avoid completion node dissection when eligibility criteria from the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial are met. The National Comprehensive Cancer Network (NCCN) recently proposed to extend this indication to patients that present with biopsy proven node positive disease if only 1 or 2 suspicious nodes are found on imaging, these positive nodes are not palpable clinically, and the other eligibility criteria from the Z0011 study are otherwise met. However, this recommendation is based on an expert consensus and no study has yet confirmed the optimal method to stage the axilla in this patient population. PURPOSE: Evaluate the technical success rate and accuracy of sentinel node biopsy (SNB) and the potential benefits of clipping and removing the biopsy proven node using radioactive seed localisation (RSL) (SNB+RSL = Targeted Axillary Dissection (TAD)) in patients with biopsy proven positive nodes, limited nodal disease in imaging and clinically negative axillary examination.

Detailed Description
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This is a prospective multicenter study. Patients with T1-2 Breast cancer and clinically negative axilla on palpation, 1-2 suspicious nodes on ultrasound, and a biopsy proven positive node (by core biopsy of fine needle aspiration) will have a radioactive seed (I125) placed in their clipped node before surgery. At the time of surgery, patients that are scheduled for breast conserving surgery or mastectomy will have sentinel node biopsy (SNB) using radioactive dye (Tc99) +/- blue dye as well as retrieval of the clipped node using radioactive seed localisation (RSL). Removal of the I125 radioactive seed in the clipped node will be performed before the Tc99 counts are performed to prevent shine through and biased measurements. Imaging of the surgical specimen will confirm retrieval of the clipped node. Prospectively recorded information on pre-operative axillary imaging, characteristics of the retrieved nodes in the operating room and detailed pathological analysis of each corresponding node will be performed. Completion node dissection (CND) is not mandatory in this study but recommended if the clipped positive node is not retrieved, if 4 nodes or more are positive or if 3 nodes are positive in the absence of axillary radiation. The benefits of adding RSL to SNB and the benefits of adding SNB to RSL staging of the axilla will be evaluated in this study and will help to better define the value of using TAD in this patient population.

Official Title
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Sentinel Node Biopsy and Targeted Axillary Dissection in Node-Positive Breast Cancer Patients With Clinically Negative Axilla

Conditions
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Sentinel Lymph Node, Breast Cancer Female, Early-stage Breast Cancer, Lymph Node Metastases, Axillary Metastases

Intervention / Treatment
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* Procedure: Targeted Axillary Dissection
* Diagnostic Test: Ultrasound of the axilla


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be ≥ 18 years old. Participants with a clinical T1 or T2 invasive ductal or lobular breast carcinoma, regardless of estrogen/progesterone/human epidermal growth factor receptor 2 (HER2) receptor status. Participants with clinical (on palpation) N0 and up to two suspicious lymph nodes on axillary ultrasound. Participant with biopsy-proven positive axillary disease made by core needle biopsy or fine-needle aspiration. Participants must have an Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status less than 2. Participants must understand, accept, and have signed the approved consent form. Exclusion Criteria: Participant with previous ipsilateral axillary surgery, including sentinel lymph node biopsy. Participants with distant metastases. Participants that have had previous radiotherapy to the axillary nodes. Participants who received neoadjuvant therapy. If the injection of blue dye is planned, patients with hypersensitivity or allergy to isosulfan blue, patent blue, methylene blue or radiocolloid dye. Participants who are unable to provide informed consent.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeted Axillary Dissection<br>Ultrasound of the axilla preoperative. Clipped biopsy proven positive node. I125 radioactive seed before surgery. Sentinel node biopsy using Tc99 +/- blue dye. Targeted Axillary Node Dissection performed at surgery | Procedure: Targeted Axillary Dissection<br>* Sentinel Node Biopsy (SNB; using Tc99 +/- Blue dye) + Radioactive Seed Localisation (RSL) of clipped node using I125 seed = Targeted Axillary Dissection (TAD)<br>Diagnostic Test: Ultrasound of the axilla<br>* Prospectively recorded preoperative ultrasound of the axilla. Number of suspicious nodes recorded. Biopsy and clipping of the positive node.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in recommended completion node dissection rate (CND) with the use of Targeted Axillary Dissection (TAD) vs. Sentinel Node Biopsy (SNB) alone. | Recommended completion node dissection rate (CND) = false negative rate (FNR) + technical failure rate (TFR). TAD CND (TAD FNR + TAD TFR) vs. SNB CND (SNB FNR + SNB TFR) | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification rate of patients with three or more positive nodes using only radioactive seed localisation (RSL) vs. Targeted Axillary Dissection (TAD) | Evaluate if the addition of SNB to RSL improves the ability to identify patients with 3+ positive nodes that do not otherwise meet the ACOSOG Z0011 criteria and require further regional axillary therapy | 1 month | 
| False negative rate (FNR) of Targeted Axillary Dissection (TAD) | Percentage of patients with successful removal of at least one node (using this method) where at least one positive node was not retrieved (using this method) | 1 month | 
| Technical failure rate (TFR) of Targeted Axillary Dissection (TAD) | Percentage of patients with unsuccessful removal of at least one node using this method, including the clipped node | 1 month | 
| False negative rate (FNR) of Radioactive Seed Localisation (RSL) | Percentage of patients with successful removal of at least one node (using this method) where at least one positive node was not retrieved (using this method) | 1 month | 
| Technical failure rate (TFR) of Radioactive Seed Localisation (RSL) | Percentage of patients with unsuccessful removal of at least one node using this method, including the clipped node | 1 month | 
| False negative rate (FNR) of Sentinel Node Biopsy (SNB) | Percentage of patients with successful removal of at least one node (using this method) where at least one positive node was not retrieved (using this method) | 1 month | 
| Technical failure rate (TFR) of Sentinel Node Biopsy (SNB) | Percentage of patients with unsuccessful removal of at least one node using this method (clipped node or not) | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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clinically negative axilla, breast cancer, targeted axillary dissection, sentinel lymph node biopsy, metastatic axillary lymph nodes