Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery

Study Overview
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Brief Summary
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Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.

Detailed Description
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Currently, axillary surgery for breast cancer is considered as staging procedure that does not seem to influence breast cancer mortality, since the risk of developing metastasis depends mainly on the biological behaviour of the primary (seed-and-soil model). Based on this, the postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. The goal of the present study is to show that early-stage breast cancer patients with reduced extent of axillary surgery are not inferior regarding disease-free survival outcome compared with the standard arm. All patients will be first randomized to either no axillary surgical intervention or axillary sentinel lymph node biopsy (SLNB). Patients with SLNB and pN+(sn) status will be secondly randomized to either SLNB alone or completion axillary lymph node dissection (ALND) in cases with less than four involved nodes (1-3 macrometastases). Patients with four or more metastatic sentinel lymph nodes should undergo completion ALND. Postoperative systemic treatment should be based on local multidisciplinary tumor board recommendation according to the current German AGO and S3 guidelines. For women who are treated with breast-conserving surgery, the most common site of local recurrence is the conserved ipsilateral breast itself. Thus, whole-breast radiation therapy after breast-conserving surgery is mandatory and should be performed according to the current guidelines (S3, AGO, DEGRO). During follow-up, patients will be assessed for disease recurrence according to standard clinical practice. History and physical examination will be performed every 6 months for the first 36 months and yearly thereafter. Annual mammography and sonography will be required; other testing will be based on symptoms and investigator preference. The total number of patients to be randomized into the trial will be approximately 7,095. An event-driven final efficacy analysis will be performed per-protocol for two primary objectives.

Official Title
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Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery in Patients With Early-stage Invasive Breast Cancer and Breast-conserving Surgery: a Randomized Prospective Surgical Trial. Intergroup-Sentinel-Mamma (INSEMA)-Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: no axillary surgery versus SLNB
* Procedure: SLNB versus completion ALND


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned Age at diagnosis at least 18 years Preoperative imaging techniques with estimated tumor size of <5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status) Clinically and sonographically tumor-free axilla prior to core biopsy (cN0/iN0) In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization No clinical evidence for distant metastasis (M0) Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation) Exclusion Criteria: History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix Time since core biopsy >3 months (optimal <1 month) Previous and already (neoadjuvant) treated invasive breast carcinoma Histologically non-invasive breast carcinoma cT3/T4 or iT3/T4 tumors pregnant or lactating patients Planned total mastectomy (e.g. multicentric tumors ) Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques Male patients

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: no axillary surgery<br> | Procedure: no axillary surgery versus SLNB<br>* in cases with newly diagnosed breast cancer and clinically negative axillary status<br>|
| Active Comparator: sentinel lymph node biopsy<br>standard arm in first randomization | Procedure: no axillary surgery versus SLNB<br>* in cases with newly diagnosed breast cancer and clinically negative axillary status<br>|
| Experimental: sentinel lymph node biopsy alone<br> | Procedure: SLNB versus completion ALND<br>* in cases with 1-3 macrometastases in sentinel lymph nodes<br>|
| Active Comparator: completion axillary lymph node dissection<br>standard arm in second randomization | Procedure: SLNB versus completion ALND<br>* in cases with 1-3 macrometastases in sentinel lymph nodes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| invasive disease-free survival (IDFS) after breast-conserving surgery | non-inferiority question | 5 years | 

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