Wide Margin vs. Narrow Margin in Postneoadjuvant Lumpectomy

Study Overview
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Brief Summary
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Breast cancer patients often receive systemic drugs as the initial curative treatment of their disease. The initial systemic therapy leads to a variable degree of tumor shrinkage. At present, there is no evidence-based consensus among breast surgeons on the optimal extent of resection after considerable tumor shrinkage and whether resection margin should be designed according to the tumor extent before treatment or the extent after treatment. This trial will help determine the optimal extent of resection in tumors that exhibits a significant change in volume after primary systemic therapy.

Detailed Description
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Primary systemic (neoadjuvant) therapy (NAT) is a widely practised curative treatment for invasive breast cancer. Neoadjuvant chemotherapy (before surgery) and adjuvant chemotherapy (after surgery) had equivalent survival rates in major randomized trials. In these studies, preoperative systemic therapy increased the patient's chance to achieve breast conservation. The down side was a clear trend towards increased ipsilateral breast tumor recurrence. Preoperative chemotherapy leads to patchy, irregular cell death known as honeycomb effect and thus may lead to a misleading false negative resection margin of a tumorectomy operation. Even with the advent of oncoplastic techniques which allowed larger resection volumes with satisfactory cosmetic results, rates of re-excision, mastectomy and local relapse did not differ from those after traditional lumpectomy operations. As of today, there is no consensus -based on evidence- on the optimal width of margin in patients who are offered breast conservative surgery (BCS) after systemic therapy. In view of the current uncertainty and lack of evidence, The present trial is designed to answer the following question (Specific aim): Does planning the resection margin according to the pre-treatment tumor extent improve the local recurrence rate in patients receiving breast conservative surgery after systemic therapy?

Official Title
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Surgical Resection Margin According to the Post-treatment Tumor Volume Versus the Pre-treatment Tumor Volume in Breast Conservative Surgery for Invasive Breast Cancer Patients Receiving Primary Systemic Therapy: Randomized Controlled Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Procedure: Bracketing
* Drug: Neoadjuvant therapy
* Procedure: Post-treatment volume margin resection
* Procedure: Pre-treatment volume margin resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy-proven diagnosis of invasive adenocarcinoma of the breast. Tumor stage T 1-4b Nodal stage N 0-2 ASA (American Society of Anesthesiologists) class I-II Exclusion Criteria: Patients opting for mastectomy. Patients advised for mastectomy by the treating physician. Patients opting for primary surgical treatment. Patients advised for primary surgical treatment by the treating physician. Metastatic patients. Multifocal tumors. Lobular neoplasia. Current pregnancy or pregnancy less than 6 months from the enrollment date. Active second cancer.

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: Post-treatment volume-resection margin<br>Lumpectomy is performed with resection margin of the clinically / radiologically identifiable post-treatment tumor. | Procedure: Bracketing<br>* At the beginning of therapy, ultrasonographic examination is used to measure the tumor in three dimensions and bracket the tumor using 4-6 metal clips which will serve as markers for the initial tumor extent in case of tumor shrinkage in response to systemic treatment.<br>Drug: Neoadjuvant therapy<br>* All patients will receive primary systemic therapy according to the current institutional guidelines. Drugs include cytotoxic chemotherapy, hormonal therapy and/or anti-HER2/neu therapy as indicated.<br>Procedure: Post-treatment volume margin resection<br>* The lumpectomy resection margin is planned according to the identifiable tumor at operation. The initial extent of the tumor at diagnosis is not taken in account. If there is complete clinical response to systemic therapy (i.e. no identifiable tumor), the center of the bracketed tissue is biopsied.<br>|
| Active Comparator: Pre-treatment volume-resection margin<br>Lumpectomy is performed with resection margin of the bracketed tissue. | Procedure: Bracketing<br>* At the beginning of therapy, ultrasonographic examination is used to measure the tumor in three dimensions and bracket the tumor using 4-6 metal clips which will serve as markers for the initial tumor extent in case of tumor shrinkage in response to systemic treatment.<br>Drug: Neoadjuvant therapy<br>* All patients will receive primary systemic therapy according to the current institutional guidelines. Drugs include cytotoxic chemotherapy, hormonal therapy and/or anti-HER2/neu therapy as indicated.<br>Procedure: Pre-treatment volume margin resection<br>* The lumpectomy includes the whole bracketed tissue to take in account the initial tumor extent before systemic therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local recurrence rate. | The rate of local recurrence at five years. | at 60 months after the date of diagnosis. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local disease-free survival. | The proportion of patients who remain free of local disease recurrence. | up to 60 months from the date of diagnosis. | 
| Disease-free survival. | The proportion of patients who remain free of disease recurrence. | up to 60 months from the date of diagnosis. | 
| Overall survival. | The proportion of patients who are alive. | up to 60 months from the date of diagnosis. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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resection margin, neoadjuvant therapy, breast conservative surgery, locally advanced breast cancer