Sentinel Lymph Node Biopsy Versus no Axillary Surgery in Early Breast Cancer

Study Overview
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Brief Summary
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The VENUS trial is a prospective, multicenter, noninferiority, randomized, controlled clinical trial that compares sentinel lymph node biopsy versus no axillary surgery in women with early breast cancer (tumor <5cm) and node-negative after clinical palpation and axillary ultrasound.

Detailed Description
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The standard approach to women with early breast cancer (BC) and clinically negative nodes is sentinel lymph node dissection (SLND). Studies showed that axillary lymph node dissection (ALND) can be safely omitted in presence of positive sentinel lymph node in patients treated with breast conserving therapy.Therefore, the pertinence of SLND in the approach to women with early BC is being questioned, once it is not injury-free. The ACOSOG Z0011 trial examined the safety of omitting ALND in patients with early BC and up to 2 positive nodes at SLND, undergoing conservative surgery plus breast radiotherapy. The 10-year worth of data from this trial strongly suggested that omitting the procedure in these restrict, well-selected, subsets of patients maybe safe. Neoadjuvant chemotherapy (NAC) may be the starting treatment step for women with aggressive BC subtypes even in early stages.The SENTINA and ACOSOG Z1071 trials revealed that for women with three or more negative nodes in SLND, the procedure's accuracy and false-negative rate lie within acceptable boundaries. Our hypothesis is that for patients with early BC (regardless of neoadjuvant systemic therapy), with clinically and ultrasound negative axilla, avoiding SLND may be safe from the oncological perspective.The VENUS trial will investigate whether there may be still room for further de-escalation of the approach to the axilla in well-selected subsets of BC patients, by including women for whom the de-escalation has not been tested in previous trials dealing with the subject. The VENUS trial is a prospective, noninferiority, multicenter, randomized controlled clinical trial that was approved by the Local Research Ethic Committee .The trial will compare SLND with no axillary surgery in women with T1-2 invasive BC and N0 disease, as ascertained after clinical palpation and axillary ultrasound. Mastectomy and primary systemic therapy are allowed whether node negative previous start the treatment . All women accrued to the trial must sign the informed consent. Randomization 1:1 will be stratified by age (≤50 and >50 years old) and clinical tumor size (≤2 cm and >2 cm). The sample size estimated is 364 women in each arm (400 to account for losses to follow-up). Sample size was calculated according to the following parameters: 90% disease-free survival in patients undergoing SLND and a minimum 85% in those not undergoing the procedure, 80% power and 95% confidence intervals, with a tolerated risk ratio of 0.8. After surgery, regardless of adjuvant therapies, and for at least 48 months, patients will undergo physical examination of their breasts and axilla every 6 months and mammography will be performed annually or at closer intervals if indicated. Adjuvant chemotherapy and radiotherapy will be performed according to the protocol of each participating center and patients without axillary surgery should be considered N0 for decision making.

Official Title
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Sentinel Lymph Node Biopsy Versus no Axillary Surgery in Early Breast Cancer Clinically and Ultrasonographically Node-negative

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: No axillary surgery
* Procedure: SLNB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women Aged 18 years or older Histologically confirmed invasive breast carcinoma (core or open biopsy), independent of hormone receptor and HER2 status Tumor smaller than 5 cm (T1 or T2) in clinical and radiological exams Clinically negative axilla Sonographically negative axilla or negative core biopsy/ fine needle biopsy (FNB) when ultrasound is suspect (lymph node tissue is required in core/FNB sample) Planned breast conservative surgery or mastectomy Written informed consent Exclusion Criteria: Previous diagnostic of any invasive neoplasia (excluded skin cancer no melanoma) Metastatic disease in biopsy or image before treatment Withdrawal from participating of the study Initiated treatment for current breast cancer prior to study enrollment Pregnancy Breastfeed

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: No axillary surgery<br> | Procedure: No axillary surgery<br>* In the study arm will be omitted surgery in axilla<br>|
| Active Comparator: Sentinel lymph node biopsy<br> | Procedure: SLNB<br>* in the control arm will be realized SLNB<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival (DFS) | Interval between the end of treatment and the diagnosis of any disease recurrence (breast, axilla or distant) by image exams or biopsy | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Defined time period between the end of treatment and the patient's death from any cause. | 5 years | 
| Locoregional free survival | Interval between the end of treatment and the diagnosis of any recorrence locoregional (breast or axilla) by biopsy | 5 years | 
| Axillary recurrence rate | Percentage of patients with disease recurrence in axilla by biopsy in each grup | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Sentinel Lymph Node