Clinical trial NCT04101851: Omission of SLNB in Triple-negative and HER2-positive Breast Cancer Patients with RCR and PCR in the Breast After NAST
Official title: 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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer Female
Breast Cancer
Keywords: sentinel lymph node biopsy
neoadjuvant systemic therapy
Lead sponsor: University of Rostock
Sponsor class: OTHER
Collaborators: name: European Breast Cancer Reseach Association of Surgical Trialists
name: University Medicine Rostock, Rostock, Germany (sponsor)
name: Else Kröner-Fresenius-Stiftung (funding)
name: German Society of Senology (funding)
First posted: 2019-09-24
Enrollment: 350
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, multi-center, single-arm
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: axillary recurrence-free survival (ARFS) after breast-conserving surgery
timeFrame: 3-year
Secondary outcomes:
measure: invasive disease-free survival
timeFrame: 5-year
measure: overall survival
timeFrame: 5-year
measure: locoregional disease-free survival
timeFrame: 5-year
measure: distant disease-free survival
timeFrame: 5-year
measure: axillary recurrence-free survival
timeFrame: 5-year
measure: Diagnostic accuracy of imaging methods for pathologic complete response (breast pCR) after NAST
timeFrame: 1-year
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Med. Universität Graz, Frauenklinik
city: Augsburg
country: Germany
facility: Praxis Dres. Heinrich & Bangerter
city: Augsburg
country: Germany
facility: Universitäts-Klinikum, Frauenklinik
city: Baden-Baden
country: Germany
facility: Klinikum Mittelbaden Brustzentrum
city: Berlin
country: Germany
facility: DRK Kliniken Köpenick, Brustzentrum
city: Berlin
country: Germany
facility: Evang. Waldkrankenhaus Spandau, Brustzentrum
city: Berlin
country: Germany
facility: Sana Klinikum Lichtenberg
city: Bochum
country: Germany
facility: Augusta-Klinik Brustzentrum
city: Borna
country: Germany
facility: Brustzentrum Nordsachsen, Frauenklinik
city: Bottrop
country: Germany
facility: Marienhospital, Klinik für Gynäkologie
city: Böblingen
country: Germany
facility: Kreiskliniken Böblingen, Frauenklinik
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum, Frauenklinik
city: Dresden
country: Germany
facility: Diakonissen-Krankenhaus Brustzentrum
city: Ebersberg
country: Germany
facility: Brustzentrum Kreisklinik Ebersberg
city: Essen
country: Germany
facility: Uni-Klinikum Essen, Frauenklinik
city: Esslingen
country: Germany
facility: Klinikum Esslingen, Frauenklinik
city: Hamburg
country: Germany
facility: Agaplesion Diakonie Klinikum, Frauenklinik
city: Hamburg
country: Germany
facility: Albertinen Krankenhaus, Gynäkologie
city: Hameln
country: Germany
facility: Sana Klinikum Hameln-Pyrmont
city: Hanau
country: Germany
facility: Klinikum Hanau GmbH, Frauenklinik
city: Hannover
country: Germany
facility: Brustzentrum Klinikum Siloah
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Frauenklinik
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Frauenklinik
city: Karlsruhe
country: Germany
facility: ViDia Christliche Kliniken, Frauenklinik
city: Kassel
country: Germany
facility: Elisabeth Krankenhaus, Brustzentrum
city: Magdeburg
country: Germany
facility: Universitäts-Klinikum Magdeburg, Frauenklinik
city: Meppen
country: Germany
facility: Ludmillenstift, Brustzentrum
city: Passau
country: Germany
facility: Klinikum Passau, Frauenklinik
city: Rostock
country: Germany
facility: Universitäts-Frauenklinik am Klinikum Südstadt
city: Schkeuditz
country: Germany
facility: Helios Klinik, Gynäkologie
city: Schwerin
country: Germany
facility: Helios Kliniken Schwerin, Frauenklinik
city: Speyer
country: Germany
facility: Diakonissen-Stiftungs-Krankenhaus, Gynäkologie
city: Stendal
country: Germany
facility: Johanniter-Krankenhaus, Frauenklinik
city: Wiesbaden
country: Germany
facility: Asklepios Paulinen Klinik, Frauenklinik
city: Wiesbaden
country: Germany
facility: Helios HSK, Brustzentrum
city: Wiesbaden
country: Germany
facility: St. Josefs-Hospital, Frauenklinik
city: Winnenden
country: Germany
facility: Rems-Murr-Klinik, Frauenklinik
city: Worms
country: Germany
facility: Stadtkrankenhaus Worms gGmbH, Brustzentrum
city: Milan
country: Italy
facility: San Raffaele Hospital, Breast Unit
city: Madrid
country: Spain
facility: Universidad de Navarra
Study officials:
affiliation: Breast Unit, San Raffaele University and Research Hospital, Milan, Italy
name: Oreste D Gentilini, MD
role: STUDY_CHAIR
affiliation: Department of Obstetrics and Gynecology, University of Rostock, Germany
name: Toralf Reimer, Prof.
role: STUDY_CHAIR
References:
citation: 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.