Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients With rCR and pCR in the Breast After NAST

November 3, 2023 updated by: Toralf Reimer, MD PhD

Omission of Sentinel Lymph Node Biopsy in Triple-negative and HER2-positive Breast Cancer Patients With Radiologic and Pathologic Complete Response in the Breast After Neoadjuvant Systemic Therapy: a Single-arm, Prospective Surgical Trial.

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.

Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to decrease, and perhaps eliminate, surgery in patients who have a pCR.

The investigators designed a clinical trial in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included and type of surgery will be defined according to the response to NAST rather than on the classical T and N status at presentation. In the planned trial, axillary surgery will be eliminated completely (no axillary sentinel lymph node biopsy [SLNB]) for initially cN0 patients with radiologic complete remission (rCR) and a breast pCR as determined in the lumpectomy specimen.

The trial design is a multicenter single-arm study with a limited number of patients (N=350) which might give practice-changing results in a short period of time, sparing the time and the costs of a randomized comparison. Patients will be recruited in European countries (Austria, Germany, Italy, and Spain) over a period of 48 months.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

EUBREAST-01 is a prospective non-randomized, single-arm surgical trial. Included patients will be recruited for the experimental arm (no axillary SLNB in cases with breast pCR after NAST) exclusively. EUBREAST-01 is an international multicentric trial and designed by European Breast Cancer Research Association of Surgical Trialists (EUBREAST). The University Medicine Rostock (Germany) will overtake the sponsorship for the trial.

Duration of recruitment is 4 years among 36 German, 10-15 Italian, 3 Spanish, and 1 Austrian study centres. The total number of patients to be recruited into the trial will be 350. All participating centres are experienced in conduction of clinical trials and stated at least a rate of 50 primary breast cancer diagnosis per year. At least 30% of all primary breast cancer are TNBC or HER2-positive tumors. The great majority of these cases will be diagnosed in tumor stage T1-T3. The NAST with chemotherapy (plus anti-HER2 therapy if HER2-positive) is standard for this cohort in Germany, Austria, Italy, and Spain.

Efficacy analyses will be conducted after a follow-up of at least 3 years for each patient regarding the primary and for the secondary outcomes. No interim analysis is planned. Patients will be assessed for disease recurrence according to standard national clinical practice. Longest follow-up is 7 years. 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.

Study Type

Interventional

Enrollment (Estimated)

350

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Graz, Austria
        • Recruiting
        • Med. Universität Graz, Frauenklinik
        • Contact:
          • Florentia Peintinger, Prof.
  • Germany
      • Augsburg, Germany
        • Recruiting
        • Praxis Dres. Heinrich & Bangerter
        • Contact:
          • Bernhard Heinrich, Dr.
      • Augsburg, Germany
        • Recruiting
        • Universitäts-Klinikum, Frauenklinik
        • Contact:
          • Nina Ditsch, Prof. Dr.
      • Baden-Baden, Germany
        • Recruiting
        • Klinikum Mittelbaden Brustzentrum
        • Contact:
          • Antje Hahn, MD
      • Berlin, Germany
        • Recruiting
        • DRK Kliniken Köpenick, Brustzentrum
        • Contact:
          • Anke Kleine-Tebbe, Dr.
      • Berlin, Germany
        • Recruiting
        • Evang. Waldkrankenhaus Spandau, Brustzentrum
        • Contact:
          • Silke Polata, Dr.
      • Bochum, Germany
        • Recruiting
        • Augusta-Klinik Brustzentrum
        • Contact:
          • Robert Radkowski, Dr.
      • Borna, Germany
        • Recruiting
        • Brustzentrum Nordsachsen, Frauenklinik
        • Contact:
          • Henning Eichler, Dr.
      • Bottrop, Germany
        • Recruiting
        • Marienhospital, Klinik für Gynäkologie
        • Contact:
          • Hans-Christian Kolberg, PhD
      • Böblingen, Germany
        • Recruiting
        • Kreiskliniken Böblingen, Frauenklinik
        • Contact:
          • Stefan P Renner, Prof.
      • Cottbus, Germany
        • Recruiting
        • Carl-Thiem-Klinikum, Frauenklinik
        • Contact:
          • Nikola Bangemann, Dr.
      • Dresden, Germany
        • Recruiting
        • Diakonissen-Krankenhaus Brustzentrum
        • Contact:
          • Stefan Ollig, MD
      • Ebersberg, Germany
        • Recruiting
        • Brustzentrum Kreisklinik Ebersberg
        • Contact:
          • Stephan Hasmüller, MD
      • Essen, Germany
        • Recruiting
        • Uni-Klinikum Essen, Frauenklinik
        • Contact:
          • Oliver Hoffmann, PD
      • Esslingen, Germany
        • Recruiting
        • Klinikum Esslingen, Frauenklinik
        • Contact:
          • Alexander Hein, PhD
      • Hamburg, Germany
        • Recruiting
        • Agaplesion Diakonie Klinikum, Frauenklinik
        • Contact:
          • Christoph Lindner, Prof. Dr.
      • Hamburg, Germany
        • Recruiting
        • Albertinen Krankenhaus, Gynäkologie
        • Contact:
          • Ulrike Dörste
      • Hanau, Germany
        • Recruiting
        • Klinikum Hanau GmbH, Frauenklinik
        • Contact:
          • Thomas Müller, Prof. Dr.
      • Hannover, Germany
        • Recruiting
        • Medizinische Hochschule Hannover, Frauenklinik
        • Contact:
          • Elna Kuehnle, Dr.
      • Hannover, Germany, 30459
        • Recruiting
        • Brustzentrum Klinikum Siloah
        • Contact:
          • Kundu Sudip, PhD
      • Heidelberg, Germany
        • Recruiting
        • Universitätsklinikum Heidelberg, Frauenklinik
        • Contact:
          • Jörg Heil, Prof. Dr.
      • Karlsruhe, Germany
        • Recruiting
        • ViDia Christliche Kliniken, Frauenklinik
        • Contact:
          • Sybille Perez, Dr.
      • Kassel, Germany
        • Recruiting
        • Elisabeth Krankenhaus, Brustzentrum
        • Contact:
          • Sabine Schmatloch, Dr.
      • Magdeburg, Germany
        • Recruiting
        • Universitäts-Klinikum Magdeburg, Frauenklinik
        • Contact:
          • Franziska Thiele, Dr.
      • Meppen, Germany
        • Recruiting
        • Ludmillenstift, Brustzentrum
        • Contact:
          • Uta Fahl, Dr.
      • Passau, Germany
        • Recruiting
        • Klinikum Passau, Frauenklinik
        • Contact:
          • Agnieszka Nolte, Dr.
      • Rostock, Germany
        • Recruiting
        • Universitäts-Frauenklinik am Klinikum Südstadt
        • Contact:
          • Angrit Stachs, PhD
      • Schkeuditz, Germany
        • Recruiting
        • Helios Klinik, Gynäkologie
        • Contact:
          • Tamene Abraham, Dr.
      • Schwerin, Germany
        • Recruiting
        • Helios Kliniken Schwerin, Frauenklinik
        • Contact:
          • Nicole Stahl, Dr.
      • Speyer, Germany
        • Recruiting
        • Diakonissen-Stiftungs-Krankenhaus, Gynäkologie
        • Contact:
          • Kilian IC Paukert, Dr.
      • Stendal, Germany
        • Recruiting
        • Johanniter-Krankenhaus, Frauenklinik
        • Contact:
          • Andrea Stefek, Dr.
      • Wiesbaden, Germany
        • Recruiting
        • Asklepios Paulinen Klinik, Frauenklinik
        • Contact:
          • Susanne Renz, Dr.
      • Wiesbaden, Germany
        • Recruiting
        • Helios HSK, Brustzentrum
        • Contact:
          • Michael Eichbaum, Prof.
      • Wiesbaden, Germany
        • Recruiting
        • St. Josefs-Hospital, Frauenklinik
        • Contact:
          • Carolin Hammerle, Dr.
      • Winnenden, Germany
        • Recruiting
        • Rems-Murr-Klinik, Frauenklinik
        • Contact:
          • Hans-Joachim Strittmatter, Prof. Dr.
      • Worms, Germany
        • Recruiting
        • Stadtkrankenhaus Worms gGmbH, Brustzentrum
        • Contact:
          • Antje Nixdorf, Dr.
  • Italy
      • Milan, Italy
        • Recruiting
        • San Raffaele Hospital, Breast Unit
        • Contact:
          • Oreste D Gentilini, Dr
  • Spain
      • Madrid, Spain, 28027
        • Recruiting
        • Universidad de Navarra
        • Contact:
          • Isabel Rubio, Dr.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Written informed consent prior to breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the European regulatory requirements
  • Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned.
  • Age at diagnosis at least 18 years
  • imaging techniques with estimated tumor stage between cT1-T3 prior to NAST
  • triple-negative or HER2-positive invasive breast cancer
  • 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
  • no evidence for distant metastasis (M0)
  • standard NAST with radiologic complete response (rCR)
  • planned breast-conserving surgery 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 last cycle of NAST >3 months (optimal <1 month)
  • histologically non-invasive breast carcinoma before NAST
  • ER-positive (>=10% positive cells on IHC)/HER2-negative disease (triple-positive tumors are allowed)
  • cT4 or iT4 tumors
  • pregnant or lactating patients
  • no radiologic complete response at the end of NAST
  • planned total mastectomy after NAST
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: No axillary SLNB
After radiologic complete remission at the end of NAST all patients will be treated with breast-conserving surgery alone without any axillary surgery. Approximately 80% of these patients will be assigned to the single study arm (no axillary SLNB) due to breast pCR (ypT0/ypTis) at the final pathology of lumpectomy.
Procedure: omission of SLNB
After radiologic complete remission at the end of NAST all patients will be treated with breast-conserving surgery alone without any axillary surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
axillary recurrence-free survival (ARFS) after breast-conserving surgery
Time Frame: 3-year
3-year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: 5-year
5-year
invasive disease-free survival
Time Frame: 5-year
5-year
locoregional disease-free survival
Time Frame: 5-year
no tumor in the ipsilateral breast or ipsilateral supraclavicular, infraclavicular, internal mammary or axillary nodes
5-year
distant disease-free survival
Time Frame: 5-year
5-year
Diagnostic accuracy of imaging methods for pathologic complete response (breast pCR) after NAST
Time Frame: 1-year
1-year
axillary recurrence-free survival
Time Frame: 5-year
5-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Toralf Reimer, MD PhD

Collaborators

European Breast Cancer Reseach Association of Surgical Trialists
University Medicine Rostock, Rostock, Germany (sponsor)
Else Kröner-Fresenius-Stiftung (funding)
German Society of Senology (funding)

Investigators

  • Study Chair: Oreste D Gentilini, MD, Breast Unit, San Raffaele University and Research Hospital, Milan, Italy
  • Study Chair: Toralf Reimer, Prof., Department of Obstetrics and Gynecology, University of Rostock, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2021

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

January 1, 2028

Study Registration Dates

First Submitted

September 21, 2019

First Submitted That Met QC Criteria

September 21, 2019

First Posted (Actual)

September 24, 2019

Study Record Updates

Last Update Posted (Actual)

November 7, 2023

Last Update Submitted That Met QC Criteria

November 3, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EUBREAST-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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