T1-T2 Breast Cancer: Comparison Between Removal and Preservation of Axillary Lymph Nodes (SINODAR ONE)

Study Overview
=================
Brief Summary
-----------------
Italian Multicentric non inferiority two-arm randomized clinical trial to verify that the experimental treatment (omission of axillary lymph node intervention) in the presence of sentinel lymph node metastases does not lead to a significant worsening in survival or in the risk of locoregional recurrence compared to standard treatment (removal of I-II level of axillary lymph nodes).

Detailed Description
-----------------
Detailed Description: The trial is a non-inferiority trial; patients, depending on intra-operative or post-operative sentinel lymph node assessment, are randomly assigned to one of the two intervention groups: group 1: removal of I-II level of axillary lymph nodes (standard treatment). Removal of at least 10 lymph nodes is recommended. group 2: no axillary lymph nodes dissection (experimental treatment). Patients for whom sentinel lymph node cannot be found, will undergo complete dissection of the axillary cavity as required by international guidelines. After surgery, according to their bio-pathological profile and to the international guidelines criteria, patients will be able to receive: no further treatment complementary radiotherapy adjuvant medical therapy (chemo and / or hormone therapy). Patients will be checked for at least 5 years in the following ways: six-monthly clinical examination for the first 5 years and yearly thereafter mammography + annual breast ultrasound annual axillary ultrasound in cases not subjected to dissection.

Official Title
-----------------
T1-T2 Breast Cancer: Comparison Between Removal and Preservation of Axillary Lymph Nodes in the Presence of Sentinel Lymph Node Metastases (SINODAR ONE)

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

Intervention / Treatment
-----------------
* Procedure: Removal of axillary lymph nodes.
* Procedure: Preservation of axillary lymph nodes


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 40 ≤75 years old Breast cancer with infiltrating histology Tumor size ≤50 mm (T1 - T2) Clinically and ultrasound node-negative (cN0) breast cancer No distant metastases (M0) No neoadjuvant therapy Negative history of previous infiltrating neoplasm Maximum number of metastatic sentinel lymph nodes: 2 Lymph node macro-metastases > 2mm Exclusion Criteria: Pregnancy or breastfeeding in progress Inflammatory breast cancer Breast cancer in situ Synchronous contralateral breast cancer Co-morbidities such as to preclude the possible use of adjuvant therapy Conditions that make it impossible to carry out a regular follow-up Other malignancies within the previous 3 years (except carcinoma in situ of the uterine cervix, basalioma or squamous cell ca or non-melanoma skin ca) Breast cancer with non-infiltrating or inflammatory histotype Tumor size> 50 mm No sentinel lymph nodes identified No positive sentinel lymph nodes (pN0) Positive sentinel lymph node number > 2 Lymph node micro-metastases <= 2

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Axillary dissection (standard treatment)<br>Axillary dissection in women with sentinel lymph node metastases. (removal of at least 10 lymph nodes recommended) | Procedure: Removal of axillary lymph nodes.<br>* Axillary dissection in patients with positive sentinel lymph node<br>|
| Experimental: Preservation of axillary lymph nodes<br>Omission of Axillary dissection in women with sentinel lymph node metastases. | Procedure: Preservation of axillary lymph nodes<br>* Preservation of axillary lymph nodes in patients with positive sentinel lymph node<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Evaluating whether, in women operated for breast cancer (T1-T2) with sentinel lymph node metastases, axillary lymph node conservation is associated with a clinically relevant prognostic worsening (OS). For all the Outcomes Statistical analysis included Kaplan-Meier Product Limit Estimator and the log-rank test | 5 years of follow up after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regional Disease Free Survival (RDFS) | Evaluating whether axillary lymph node preservation is associated with a clinically relevant increase of local recurrence rate (ipsilateral axillary and supraclavicular lymph nodes). | 5 years of follow up after surgery | 
| Disease-free distance survival (DDFS) | Evaluating whether axillary lymph node preservation is associated with a clinically relevant increase in distant recurrence rate. | 5 years of follow up after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
axillary dissection, axillary lymph preservation