Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases. A Randomized Trial.

Study Overview
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Brief Summary
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Since the introduction of sentinel node biopsy in breast cancer, it has become clear that its use is reliable and reproducible. Today, it is clinical routine to not remove further lymph nodes from the axilla (arm pit) in case the sentinel node (which is the first lymph node/s reached by lymphatic flow from the breast) is free of tumor deposits. It is also routine to leave remaining lymph nodes behind in case the sentinel node contains a minimal cluster of tumor cells, called isolated tumor cells (formerly submicrometastasis). Even in slightly larger tumor deposits, so called micrometastasis (up to 2 mm in size), it has been shown that a completion axillary clearance (removal of further lymph nodes from the arm pit) does not contribute to a better survival. Data from a randomized study indicate that it seems safe to omit axillary clearance even if the sentinel node biopsy shows up to 2 nodes with tumor deposits over 2 mm in size (macrometastasis). These studies have changed clinical practice in many countries, however, it is still debated whether it is safe to omit axillary clearance in the case of sentinel node macrometastasis due to under-recruitment in the aforementioned study. The rationale for omitting extensive axillary surgery is the avoidance of postoperative morbidity such as arm lymphedema, loss of sensation, pain and swelling. The hypothesis is that refraining from axillary clearance in breast cancer patients with 1-2 sentinel nodes with macrometastasis will not worsen breast cancer-specific survival by more than a maximum of 2.5% after 5 years. This study is a prospective international randomized trial including 3500 patients. Breast cancer patients without signs of axillary nodal involvement will be eligible for sentinel node biopsy. Those who are found to have up to two sentinel node containing macrometastasis will be informed about this trial Those wishing to participate will be randomized to either undergo further axillary surgery (clearance) or not. Outcome measures are breast cancer-specific survival, disease-free survival, axillary recurrence rate and overall survival.

Detailed Description
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Details can be found on www.senomac.se

Official Title
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Survival and Axillary Recurrence Following Sentinel Node-positive Breast Cancer Without Completion Axillary Lymph Node Dissection - a Randomized Study of Patients With Macrometastases in the Sentinel Node

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: Omission of axillary clearance


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with invasive breast cancer (T1-T3) N0 on palpation Preoperative ultrasound performed Pathology report shows macrometastasis in 1-2 sentinel lymph nodes Patients undergo breast-conserving therapy or mastectomy The patient must have provided oral and written consent Age ≥ 18 years Exclusion Criteria: Metastases outside of the ipsilateral axilla Prior history of invasive breast cancer Pregnancy Bilateral breast cancer if one side meets exclusion criteria Medical contraindication for radiotherapy or systemic treatment Inability to absorb or understand the meaning of the study information; for example, through disability, inadequate language skills or dementia.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| No Intervention: Axillary clearance<br>Patients in this arm will be treated by completion axillary clearance after a sentinel node biopsy showing 1-2 nodes with macrometastasis | |
| Experimental: No axillary clearance<br>Patients in this arm will not undergo further axillary surgery after a sentinel node biopsy showing 1-2 nodes with macrometastasis | Procedure: Omission of axillary clearance<br>* The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| breast cancer-specific survival | death due to breast cancer in both arms measured at a median follow-up of 5, 10 and 15 years | up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | Breast cancer recurrence rate in both arms after a median follow-up of 5, 10 and 15 years | 5, 10 and 15 years | 
| axillary recurrence rate | The rate of axillary relapse in specific after a median follow-up of 5, 10 and 15 years | 5, 10 and 15 years | 
| overall survival | The rate of overall deaths after a median follow-up of 5, 10 and 15 years | 5, 10 and 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sentinel node biopsy, lymph node metastasis, survival