Sentinel Node Biopsy in Breast Cancer: Omission of Axillary Clearance After Macrometastases. A Randomized Trial.

NCT ID: NCT02240472

Last Updated: 2025-03-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

2700 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-27

Study Completion Date

2031-12-31

Brief Summary

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Since the introduction of sentinel node biopsy in breast cancer, it has become clear that its use is reliable and reproducible. Today, it is clinical routine to not remove further lymph nodes from the axilla (arm pit) in case the sentinel node (which is the first lymph node/s reached by lymphatic flow from the breast) is free of tumor deposits. It is also routine to leave remaining lymph nodes behind in case the sentinel node contains a minimal cluster of tumor cells, called isolated tumor cells (formerly submicrometastasis). Even in slightly larger tumor deposits, so called micrometastasis (up to 2 mm in size), it has been shown that a completion axillary clearance (removal of further lymph nodes from the arm pit) does not contribute to a better survival. Data from a randomized study indicate that it seems safe to omit axillary clearance even if the sentinel node biopsy shows up to 2 nodes with tumor deposits over 2 mm in size (macrometastasis). These studies have changed clinical practice in many countries, however, it is still debated whether it is safe to omit axillary clearance in the case of sentinel node macrometastasis due to under-recruitment in the aforementioned study. The rationale for omitting extensive axillary surgery is the avoidance of postoperative morbidity such as arm lymphedema, loss of sensation, pain and swelling.

The hypothesis is that refraining from axillary clearance in breast cancer patients with 1-2 sentinel nodes with macrometastasis will not worsen breast cancer-specific survival by more than a maximum of 2.5% after 5 years.

This study is a prospective international randomized trial including 3500 patients.

Breast cancer patients without signs of axillary nodal involvement will be eligible for sentinel node biopsy. Those who are found to have up to two sentinel node containing macrometastasis will be informed about this trial Those wishing to participate will be randomized to either undergo further axillary surgery (clearance) or not. Outcome measures are breast cancer-specific survival, disease-free survival, axillary recurrence rate and overall survival.

Detailed Description

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Details can be found on www.senomac.se

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Axillary clearance

Patients in this arm will be treated by completion axillary clearance after a sentinel node biopsy showing 1-2 nodes with macrometastasis

Group Type NO_INTERVENTION

No interventions assigned to this group

No axillary clearance

Patients in this arm will not undergo further axillary surgery after a sentinel node biopsy showing 1-2 nodes with macrometastasis

Group Type EXPERIMENTAL

Omission of axillary clearance

Intervention Type PROCEDURE

The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis

Interventions

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Omission of axillary clearance

The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Patients with invasive breast cancer (T1-T3)
* N0 on palpation
* Preoperative ultrasound performed
* Pathology report shows macrometastasis in 1-2 sentinel lymph nodes
* Patients undergo breast-conserving therapy or mastectomy
* The patient must have provided oral and written consent
* Age ≥ 18 years

Exclusion Criteria

* Metastases outside of the ipsilateral axilla
* Prior history of invasive breast cancer
* Pregnancy
* Medical contraindication for radiotherapy or systemic treatment
* Inability to absorb or understand the meaning of the study information; for example, through disability, inadequate language skills or dementia.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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The Swedish Research Council

OTHER_GOV

Sponsor Role collaborator

Swedish Cancer Foundation

OTHER

Sponsor Role collaborator

Nordic Cancer Union

OTHER

Sponsor Role collaborator

Karolinska Institutet

OTHER

Sponsor Role lead

Responsible Party

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Jana de Boniface

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jana de Boniface, PhD

Role: PRINCIPAL_INVESTIGATOR

Karolinska Institutet

Jan Frisell, Professor

Role: STUDY_CHAIR

Karolinska University Hospital

Leif Bergkvist, Professor

Role: STUDY_CHAIR

Central Hospital Västerås

Yvette Andersson, PhD

Role: STUDY_CHAIR

Central Hospital Västerås

Lisa Ryden, Professor

Role: STUDY_CHAIR

Lund University

Malin Sund, Professor

Role: STUDY_CHAIR

Umeå University Hospital

Olofsson Roger, PhD

Role: STUDY_CHAIR

Sahlgrenska University Hospital

Johan Ahlgren, PhD

Role: STUDY_CHAIR

Region Örebro County

Dan Lundstedt, PhD

Role: STUDY_CHAIR

Sahlgrenska University Hospital

Peer Christiansen, Professor

Role: PRINCIPAL_INVESTIGATOR

Aarhus University Hospital, Denmark

Tove Tvedskov Filtenborg, MD

Role: STUDY_CHAIR

Rigshospitalet Copenhagen, Dnmark

Michalis Kontos, PhD

Role: STUDY_CHAIR

University of Athens

Birgitte Offersen, Professor

Role: STUDY_CHAIR

University of Aarhus

Thorsten Kühn, Professor

Role: PRINCIPAL_INVESTIGATOR

Klinikum Esslingen

Toralf Reimer, Professor

Role: PRINCIPAL_INVESTIGATOR

Universität Rostock

Oreste Gentilini

Role: PRINCIPAL_INVESTIGATOR

San Raffaele Hospital, Milano

Roland Reitsamer

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Salzburg

Locations

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Sygehus Sonderjylland

Aabenraa, , Denmark

Site Status

Aalborg University Hospital

Aalborg, , Denmark

Site Status

Aarhus University Hospital

Aarhus, , Denmark

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Sydvestjysk Sygehus

Esbjerg, , Denmark

Site Status

Sygehus Lillebaelt

Lillebaelt, , Denmark

Site Status

Odense University Hospital

Odense, , Denmark

Site Status

Randers Regionshospitalet

Randers, , Denmark

Site Status

Regionshospitalet Viborg

Viborg, , Denmark

Site Status

Athens University Hospital

Athens, , Greece

Site Status

Gävle sjukhus

Gävle, , Sweden

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Hallands sjukhus

Halmstad, , Sweden

Site Status

Helsingborg lasarett

Helsingborg, , Sweden

Site Status

Länssjukhuset Ryhov

Jönköping, , Sweden

Site Status

Kalmar sjukhus

Kalmar, , Sweden

Site Status

Blekinge sjukhuset

Karlskrona, , Sweden

Site Status

Karlstad sjukhus

Karlstad, , Sweden

Site Status

Central Hospital Kristianstad

Kristianstad, , Sweden

Site Status

Linköping University Hospital

Linköping, , Sweden

Site Status

Malmö/Lund University Hospital

Lund, , Sweden

Site Status

Örebro University Hospital

Örebro, , Sweden

Site Status

Skaraborgs sjukhus

Skövde/Lidköping, , Sweden

Site Status

Karolinska University Hospital

Stockholm, , Sweden

Site Status

Southern Gerenal Hospital

Stockholm, , Sweden

Site Status

St. Görans Hospital

Stockholm, , Sweden

Site Status

Sundsvall länssjukhus

Sundsvall, , Sweden

Site Status

Uddevalla sjukhus

Uddevalla, , Sweden

Site Status

Umeå University Hospital

Umeå, , Sweden

Site Status

Akademiska Sjukhuset

Uppsala, , Sweden

Site Status

Varbergs sjukhus

Varberg, , Sweden

Site Status

Västerås Central Hospital

Västerås, , Sweden

Site Status

Västervik Hospital

Västervik, , Sweden

Site Status

Countries

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Denmark Greece Sweden

References

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Skarping I, Bendahl PO, Szulkin R, Alkner S, Andersson Y, Bergkvist L, Christiansen P, Filtenborg Tvedskov T, Frisell J, Gentilini OD, Kontos M, Kuhn T, Lundstedt D, Vrou Offersen B, Olofsson Bagge R, Reimer T, Sund M, Ryden L, de Boniface J. Prediction of High Nodal Burden in Patients With Sentinel Node-Positive Luminal ERBB2-Negative Breast Cancer. JAMA Surg. 2024 Dec 1;159(12):1393-1403. doi: 10.1001/jamasurg.2024.3944.

Reference Type DERIVED
PMID: 39320882 (View on PubMed)

de Boniface J, Appelgren M, Szulkin R, Alkner S, Andersson Y, Bergkvist L, Frisell J, Gentilini OD, Kontos M, Kuhn T, Lundstedt D, Offersen BV, Olofsson Bagge R, Reimer T, Sund M, Christiansen P, Ryden L, Filtenborg Tvedskov T; SENOMAC Trialists' Group. Completion axillary lymph node dissection for the identification of pN2-3 status as an indication for adjuvant CDK4/6 inhibitor treatment: a post-hoc analysis of the randomised, phase 3 SENOMAC trial. Lancet Oncol. 2024 Sep;25(9):1222-1230. doi: 10.1016/S1470-2045(24)00350-4. Epub 2024 Aug 6.

Reference Type DERIVED
PMID: 39121881 (View on PubMed)

de Boniface J, Filtenborg Tvedskov T, Ryden L, Szulkin R, Reimer T, Kuhn T, Kontos M, Gentilini OD, Olofsson Bagge R, Sund M, Lundstedt D, Appelgren M, Ahlgren J, Norenstedt S, Celebioglu F, Sackey H, Scheel Andersen I, Hoyer U, Nyman PF, Vikhe Patil E, Wieslander E, Dahl Nissen H, Alkner S, Andersson Y, Offersen BV, Bergkvist L, Frisell J, Christiansen P; SENOMAC Trialists' Group; SENOMAC Trialists' Group. Omitting Axillary Dissection in Breast Cancer with Sentinel-Node Metastases. N Engl J Med. 2024 Apr 4;390(13):1163-1175. doi: 10.1056/NEJMoa2313487.

Reference Type DERIVED
PMID: 38598571 (View on PubMed)

Appelgren M, Sackey H, Wengstrom Y, Johansson K, Ahlgren J, Andersson Y, Bergkvist L, Frisell J, Lundstedt D, Ryden L, Sund M, Alkner S, Vrou Offersen B, Filtenborg Tvedskov T, Christiansen P, de Boniface J; SENOMAC Trialists' Group. Patient-reported outcomes one year after positive sentinel lymph node biopsy with or without axillary lymph node dissection in the randomized SENOMAC trial. Breast. 2022 Jun;63:16-23. doi: 10.1016/j.breast.2022.02.013. Epub 2022 Mar 1.

Reference Type DERIVED
PMID: 35279508 (View on PubMed)

de Boniface J, Ahlgren J, Andersson Y, Bergkvist L, Frisell J, Lundstedt D, Olofsson Bagge R, Ryden L, Sund M; SENOMAC Trialists' Group. The generalisability of randomised clinical trials: an interim external validity analysis of the ongoing SENOMAC trial in sentinel lymph node-positive breast cancer. Breast Cancer Res Treat. 2020 Feb;180(1):167-176. doi: 10.1007/s10549-020-05537-1. Epub 2020 Jan 27.

Reference Type DERIVED
PMID: 31989379 (View on PubMed)

de Boniface J, Frisell J, Andersson Y, Bergkvist L, Ahlgren J, Ryden L, Olofsson Bagge R, Sund M, Johansson H, Lundstedt D; SENOMAC Trialists' Group. Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial. BMC Cancer. 2017 May 26;17(1):379. doi: 10.1186/s12885-017-3361-y.

Reference Type DERIVED
PMID: 28549453 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Study Documents

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Document Type: Study Protocol

Study protocol and patient information (English)

View Document

Related Links

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http://senomac.se

study homepage

Other Identifiers

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SENOMAC

Identifier Type: -

Identifier Source: org_study_id

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