Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients with RCR and PCR in the Breast After NAST

NCT ID: NCT04101851

Last Updated: 2025-01-07

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-13
• Study Completion Date: 2028-01-31

Brief Summary

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.

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.

Conditions

Breast Cancer Female; Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

omission of SLNB

Intervention Type: PROCEDURE

After radiologic complete remission at the end of NAST all patients will be treated with breast-conserving surgery alone without any axillary surgery.

Interventions

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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

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

Sponsors

European Breast Cancer Research Association of Surgical Trialists

NETWORK

Sponsor Role: collaborator

University Medicine Rostock, Rostock, Germany (sponsor)

UNKNOWN

Sponsor Role: collaborator

Else Kröner-Fresenius-Stiftung (funding)

UNKNOWN

Sponsor Role: collaborator

German Society of Senology (funding)

UNKNOWN

Sponsor Role: collaborator

Toralf Reimer, MD PhD

OTHER

Sponsor Role: lead

Responsible Party

Toralf Reimer, MD PhD

Deputy director, Department of Obstetrics and Gynecology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Oreste D Gentilini, MD

Role: STUDY_CHAIR

Breast Unit, San Raffaele University and Research Hospital, Milan, Italy

Toralf Reimer, Prof.

Role: STUDY_CHAIR

Department of Obstetrics and Gynecology, University of Rostock, Germany

Locations

Med. Universität Graz, Frauenklinik

Graz, , Austria

Praxis Dres. Heinrich & Bangerter

Augsburg, , Germany

Universitäts-Klinikum, Frauenklinik

Augsburg, , Germany

Klinikum Mittelbaden Brustzentrum

Baden-Baden, , Germany

DRK Kliniken Köpenick, Brustzentrum

Berlin, , Germany

Evang. Waldkrankenhaus Spandau, Brustzentrum

Berlin, , Germany

Sana Klinikum Lichtenberg

Berlin, , Germany

Augusta-Klinik Brustzentrum

Bochum, , Germany

Brustzentrum Nordsachsen, Frauenklinik

Borna, , Germany

Marienhospital, Klinik für Gynäkologie

Bottrop, , Germany

Kreiskliniken Böblingen, Frauenklinik

Böblingen, , Germany

Carl-Thiem-Klinikum, Frauenklinik

Cottbus, , Germany

Diakonissen-Krankenhaus Brustzentrum

Dresden, , Germany

Brustzentrum Kreisklinik Ebersberg

Ebersberg, , Germany

Uni-Klinikum Essen, Frauenklinik

Essen, , Germany

Klinikum Esslingen, Frauenklinik

Esslingen am Neckar, , Germany

Agaplesion Diakonie Klinikum, Frauenklinik

Hamburg, , Germany

Albertinen Krankenhaus, Gynäkologie

Hamburg, , Germany

Sana Klinikum Hameln-Pyrmont

Hamelin, , Germany

Klinikum Hanau GmbH, Frauenklinik

Hanau, , Germany

Brustzentrum Klinikum Siloah

Hanover, , Germany

Medizinische Hochschule Hannover, Frauenklinik

Hanover, , Germany

Universitätsklinikum Heidelberg, Frauenklinik

Heidelberg, , Germany

ViDia Christliche Kliniken, Frauenklinik

Karlsruhe, , Germany

Elisabeth Krankenhaus, Brustzentrum

Kassel, , Germany

Universitäts-Klinikum Magdeburg, Frauenklinik

Magdeburg, , Germany

Ludmillenstift, Brustzentrum

Meppen, , Germany

Klinikum Passau, Frauenklinik

Passau, , Germany

Universitäts-Frauenklinik am Klinikum Südstadt

Rostock, , Germany

Helios Klinik, Gynäkologie

Schkeuditz, , Germany

Helios Kliniken Schwerin, Frauenklinik

Schwerin, , Germany

Diakonissen-Stiftungs-Krankenhaus, Gynäkologie

Speyer, , Germany

Johanniter-Krankenhaus, Frauenklinik

Stendal, , Germany

Asklepios Paulinen Klinik, Frauenklinik

Wiesbaden, , Germany

Helios HSK, Brustzentrum

Wiesbaden, , Germany

St. Josefs-Hospital, Frauenklinik

Wiesbaden, , Germany

Rems-Murr-Klinik, Frauenklinik

Winnenden, , Germany

Stadtkrankenhaus Worms gGmbH, Brustzentrum

Worms, , Germany

San Raffaele Hospital, Breast Unit

Milan, , Italy

Universidad de Navarra

Madrid, , Spain

Countries

Austria; Germany; Italy; Spain

References

Reimer T, Glass A, Botteri E, Loibl S, D Gentilini O. Avoiding Axillary Sentinel Lymph Node Biopsy after Neoadjuvant Systemic Therapy in Breast Cancer: Rationale for the Prospective, Multicentric EUBREAST-01 Trial. Cancers (Basel). 2020 Dec 9;12(12):3698. doi: 10.3390/cancers12123698.

Reference Type: BACKGROUND

PMID: 33317077 (View on PubMed)

Related Links

https://eubreast.com

Related Info

Other Identifiers

EUBREAST-01

Identifier Type: -

Identifier Source: org_study_id