Wide Margin vs. Narrow Margin in Postneoadjuvant Lumpectomy

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Procedure: Bracketing; Drug: Neoadjuvant therapy; Procedure: Post-treatment volume margin resection; Procedure: Pre-treatment volume margin resection

Detailed Description

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?

• Study Type: Interventional
• Enrollment (Anticipated): 370
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Osama Hussein, MD,PhD,FEBS; Phone Number: +2010 9981 5110; Email: osamahussein@mans.edu.eg

Study Locations

• Egypt
  • DK
    • Mansourah, DK, Egypt, 35516
      • Recruiting
      • Mansoura University Oncology Center
      • Contact: Osama Hussein, MD,PhD,FEBS; Phone Number: +2010 9981 5110; Email: osamahussein@mans.edu.eg
      • Sub-Investigator: Aiman El-Saed, MD,PhD
      • Sub-Investigator: Maha El-Zaafarany, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Post-treatment volume-resection margin; Lumpectomy is performed with resection margin of the clinically / radiologically identifiable post-treatment tumor.	Procedure: Bracketing; 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.; Drug: Neoadjuvant therapy; 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.; Procedure: Post-treatment volume margin resection; 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.
Active Comparator: Pre-treatment volume-resection margin; Lumpectomy is performed with resection margin of the bracketed tissue.	Procedure: Bracketing; 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.; Drug: Neoadjuvant therapy; 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.; Procedure: Pre-treatment volume margin resection; The lumpectomy includes the whole bracketed tissue to take in account the initial tumor extent before systemic therapy.

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mastectomy rate.	The proportion of patients who undergo mastectomy after failed conservative surgery.	at 6 months from the date of first surgical intervention.
Cosmetic score.	Numeric score description of the cosmetic outcome of breast conservative surgery.	at 6 months from the date of first surgical intervention.

Collaborators and Investigators

• Sponsor: Mansoura University

Publications and helpful links

General Publications

• Zhou X, Li Y. Local Recurrence after Breast-Conserving Surgery and Mastectomy Following Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer - a Meta-Analysis. Breast Care (Basel). 2016 Oct;11(5):345-351. doi: 10.1159/000450626. Epub 2016 Oct 14.
• Gnant M, Harbeck N, Thomssen C. St. Gallen/Vienna 2017: A Brief Summary of the Consensus Discussion about Escalation and De-Escalation of Primary Breast Cancer Treatment. Breast Care (Basel). 2017 May;12(2):102-107. doi: 10.1159/000475698. Epub 2017 Apr 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Anticipated): August 1, 2026
• Study Completion (Anticipated): August 1, 2026

Study Registration Dates

• First Submitted: January 24, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: neoadjuvant therapy; resection margin; locally advanced breast cancer; breast conservative surgery
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: R.18.02.33

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No