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

NCT02240472 | Active Not Recruiting DMC

• 1 other identifier: SENOMAC
• Study Type: interventional
• Target: 2,700
• Locations: 3 countries
• Sites: 33

Brief Summary

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.

Conditions

Breast Cancer

Keywords

sentinel node biopsy, lymph node metastasis, survival

Outcome Measures

Primary Outcomes (1)

• breast cancer-specific survival

  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 Outcomes (3)

• disease-free survival

  5, 10 and 15 years

• axillary recurrence rate

  5, 10 and 15 years

• overall survival

  5, 10 and 15 years

Study Arms (2)

Axillary clearance

NO INTERVENTION

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

No axillary clearance

EXPERIMENTAL

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

Interventions

Omission of axillary clearance PROCEDURE

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

No axillary clearance

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska Institutet: lead
• The Swedish Research Council: collaborator
• Swedish Cancer Foundation: collaborator
• Nordic Cancer Union: collaborator

Study Sites (33)

Sygehus Sonderjylland

Aabenraa, Denmark

Location

Aalborg University Hospital

Aalborg, Denmark

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Rigshospitalet

Copenhagen, Denmark

Location

Sydvestjysk Sygehus

Esbjerg, Denmark

Location

Sygehus Lillebaelt

Lillebaelt, Denmark

Location

Odense University Hospital

Odense, Denmark

Location

Randers Regionshospitalet

Randers, Denmark

Location

Regionshospitalet Viborg

Viborg, Denmark

Location

Athens University Hospital

Athens, Greece

Location

Gävle sjukhus

Gävle, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Hallands sjukhus

Halmstad, Sweden

Location

Helsingborg lasarett

Helsingborg, Sweden

Location

Länssjukhuset Ryhov

Jönköping, Sweden

Location

Kalmar sjukhus

Kalmar, Sweden

Location

Blekinge sjukhuset

Karlskrona, Sweden

Location

Karlstad sjukhus

Karlstad, Sweden

Location

Central Hospital Kristianstad

Kristianstad, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Malmö/Lund University Hospital

Lund, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Skaraborgs sjukhus

Skövde/Lidköping, Sweden

Location

Karolinska University Hospital

Stockholm, Sweden

Location

Southern Gerenal Hospital

Stockholm, Sweden

Location

St. Görans Hospital

Stockholm, Sweden

Location

Sundsvall länssjukhus

Sundsvall, Sweden

Location

Uddevalla sjukhus

Uddevalla, Sweden

Location

Umeå University Hospital

Umeå, Sweden

Location

Akademiska Sjukhuset

Uppsala, Sweden

Location

Varbergs sjukhus

Varberg, Sweden

Location

Västerås Central Hospital

Västerås, Sweden

Location

Västervik Hospital

Västervik, Sweden

Location

Related Publications (6)

• 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.

  PMID: 39320882 DERIVED

• 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.

  PMID: 39121881 DERIVED

• 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.

  PMID: 38598571 DERIVED

• 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.

  PMID: 35279508 DERIVED

• 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.

  PMID: 31989379 DERIVED

• 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.

  PMID: 28549453 DERIVED

Related Links

• study homepage

MeSH Terms

Conditions

Breast Neoplasms; Lymphatic Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jana de Boniface, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• 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

  Umeå University Hospital

  STUDY CHAIR

• Olofsson Roger, PhD

  Sahlgrenska University Hospital

  STUDY CHAIR

• Johan Ahlgren, PhD

  Region Örebro County

  STUDY CHAIR

• Dan Lundstedt, PhD

  Sahlgrenska University Hospital

  STUDY CHAIR

• Peer Christiansen, Professor

  Aarhus University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

• Tove Tvedskov Filtenborg, MD

  Rigshospitalet Copenhagen, Dnmark

  STUDY CHAIR

• Michalis Kontos, PhD

  University of Athens

  STUDY CHAIR

• Birgitte Offersen, Professor

  University of Aarhus

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2014
• First Posted: September 15, 2014
• Study Start: January 27, 2015
• Primary Completion: December 31, 2021
• Study Completion (Estimated): December 31, 2031
• Last Updated: March 4, 2025

Record last verified: 2025-03

Locations

DK (9); GR (1); SE (23)