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

March 3, 2025 updated by: Jana de Boniface, Karolinska Institutet

Survival and Axillary Recurrence Following Sentinel Node-positive Breast Cancer Without Completion Axillary Lymph Node Dissection - a Randomized Study of Patients With Macrometastases in the Sentinel Node

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Details can be found on www.senomac.se

Study Type

Interventional

Enrollment (Actual)

2700

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 Locations

  • Denmark
      • Aabenraa, Denmark
        • Sygehus Sonderjylland
      • Aalborg, Denmark
        • Aalborg University Hospital
      • Aarhus, Denmark
        • Aarhus University Hospital
      • Copenhagen, Denmark
        • Rigshospitalet
      • Esbjerg, Denmark
        • Sydvestjysk Sygehus
      • Lillebaelt, Denmark
        • Sygehus Lillebaelt
      • Odense, Denmark
        • Odense University Hospital
      • Randers, Denmark
        • Randers Regionshospitalet
      • Viborg, Denmark
        • Regionshospitalet Viborg
  • Greece
      • Athens, Greece
        • Athens University Hospital
  • Sweden
      • Gävle, Sweden
        • Gävle sjukhus
      • Göteborg, Sweden
        • Sahlgrenska University Hospital
      • Halmstad, Sweden
        • Hallands Sjukhus
      • Helsingborg, Sweden
        • Helsingborg lasarett
      • Jönköping, Sweden
        • Länssjukhuset Ryhov
      • Kalmar, Sweden
        • Kalmar sjukhus
      • Karlskrona, Sweden
        • Blekinge sjukhuset
      • Karlstad, Sweden
        • Karlstad sjukhus
      • Kristianstad, Sweden
        • Central Hospital Kristianstad
      • Linköping, Sweden
        • Linköping University Hospital
      • Lund, Sweden
        • Malmö/Lund University Hospital
      • Skövde/Lidköping, Sweden
        • Skaraborgs Sjukhus
      • Stockholm, Sweden
        • Karolinska University Hospital
      • Stockholm, Sweden
        • Southern Gerenal Hospital
      • Stockholm, Sweden
        • St. Görans Hospital
      • Sundsvall, Sweden
        • Sundsvall länssjukhus
      • Uddevalla, Sweden
        • Uddevalla Sjukhus
      • Umeå, Sweden
        • Umea University Hospital
      • Uppsala, Sweden
        • Akademiska Sjukhuset
      • Varberg, Sweden
        • Varbergs sjukhus
      • Västervik, Sweden
        • Västervik Hospital
      • Västerås, Sweden
        • Västerås Central Hospital
      • Örebro, Sweden
        • Orebro University Hospital

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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
  • Bilateral breast cancer if one side meets exclusion criteria
  • 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.

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Axillary clearance
Patients in this arm will be treated by completion axillary clearance after a sentinel node biopsy showing 1-2 nodes with macrometastasis
Experimental: No axillary clearance
Patients in this arm will not undergo further axillary surgery after a sentinel node biopsy showing 1-2 nodes with macrometastasis
Procedure: Omission of axillary clearance
The intervention is the omission of completion axillary clearance after the detection of sentinel node macrometastasis

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
breast cancer-specific survival
Time Frame: up to 15 years
death due to breast cancer in both arms measured at a median follow-up of 5, 10 and 15 years
up to 15 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
disease-free survival
Time Frame: 5, 10 and 15 years
Breast cancer recurrence rate in both arms after a median follow-up of 5, 10 and 15 years
5, 10 and 15 years
axillary recurrence rate
Time Frame: 5, 10 and 15 years
The rate of axillary relapse in specific after a median follow-up of 5, 10 and 15 years
5, 10 and 15 years
overall survival
Time Frame: 5, 10 and 15 years
The rate of overall deaths after a median follow-up of 5, 10 and 15 years
5, 10 and 15 years

Collaborators and Investigators

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

Sponsor

Karolinska Institutet

Collaborators

The Swedish Research Council
Swedish Cancer Foundation
Nordic Cancer Union

Investigators

  • Principal Investigator: Jana de Boniface, PhD, Karolinska Institutet
  • Study Chair: Jan Frisell, Professor, Karolinska University Hospital
  • Study Chair: Leif Bergkvist, Professor, Central Hospital Västerås
  • Study Chair: Yvette Andersson, PhD, Central Hospital Västerås
  • Study Chair: Lisa Ryden, Professor, Lund University
  • Study Chair: Malin Sund, Professor, Umea University Hospital
  • Study Chair: Johan Ahlgren, PhD, Region Örebro county
  • Principal Investigator: Peer Christiansen, Professor, Aarhus University Hospital, Denmark
  • Study Chair: Tove Tvedskov Filtenborg, MD, Rigshospitalet Copenhagen, Dnmark
  • Study Chair: Michalis Kontos, PhD, University of Athens
  • Study Chair: Birgitte Offersen, Professor, University of Aarhus
  • Principal Investigator: Thorsten Kühn, Professor, Klinikum Esslingen
  • Principal Investigator: Toralf Reimer, Professor, Universität Rostock
  • Principal Investigator: Oreste Gentilini, San Raffaele Hospital, Milano
  • Principal Investigator: Roland Reitsamer, Universitätsklinikum Salzburg
  • Study Chair: Olofsson Roger, PhD, Sahlgrenska University Hospital
  • Study Chair: Dan Lundstedt, PhD, Sahlgrenska University Hospital

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 27, 2015

Primary Completion (Actual)

December 31, 2021

Study Completion (Estimated)

December 31, 2031

Study Registration Dates

First Submitted

September 11, 2014

First Submitted That Met QC Criteria

September 12, 2014

First Posted (Estimated)

September 15, 2014

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 3, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SENOMAC

Plan for Individual participant data (IPD)

Study Data/Documents

  1. Study Protocol
    Information comments: Study protocol and patient information (English)

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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