Wide Margin vs. Narrow Margin in Postneoadjuvant Lumpectomy

NCT ID: NCT03417622

Last Updated: 2021-02-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 370 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-01
• Study Completion Date: 2026-08-01

Brief Summary

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

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?

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Post-treatment volume-resection margin

Lumpectomy is performed with resection margin of the clinically / radiologically identifiable post-treatment tumor.

Group Type: EXPERIMENTAL

Bracketing

Intervention Type: PROCEDURE

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.

Neoadjuvant therapy

Intervention Type: DRUG

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.

Post-treatment volume margin resection

Intervention Type: PROCEDURE

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.

Pre-treatment volume-resection margin

Lumpectomy is performed with resection margin of the bracketed tissue.

Group Type: ACTIVE_COMPARATOR

Bracketing

Intervention Type: PROCEDURE

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.

Neoadjuvant therapy

Intervention Type: DRUG

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.

Pre-treatment volume margin resection

Intervention Type: PROCEDURE

The lumpectomy includes the whole bracketed tissue to take in account the initial tumor extent before systemic therapy.

Interventions

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.

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Pre-treatment volume margin resection

The lumpectomy includes the whole bracketed tissue to take in account the initial tumor extent before systemic therapy.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mansoura University

OTHER

Sponsor Role: lead

Responsible Party

Osama Hussein

Professor of surgery (surgical oncology)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Mansoura University Oncology Center

Al Mansurah, DK, Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Osama Hussein, MD,PhD,FEBS

Role: CONTACT

osamahussein@mans.edu.eg

+2010 9981 5110

Facility Contacts

Osama Hussein, MD,PhD,FEBS

Role: primary

osamahussein@mans.edu.eg

+2010 9981 5110

References

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.

Reference Type: BACKGROUND

PMID: 27920628 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28559767 (View on PubMed)

Other Identifiers

R.18.02.33

Identifier Type: -

Identifier Source: org_study_id