Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery
INSEMA
1 other identifier
interventional
5,505
2 countries
150
Brief Summary
Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable breast-cancer
Started Sep 2015
Longer than P75 for not_applicable breast-cancer
150 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 4, 2015
CompletedFirst Posted
Study publicly available on registry
June 9, 2015
CompletedStudy Start
First participant enrolled
September 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 30, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
ExpectedMay 1, 2026
April 1, 2026
9 years
June 4, 2015
April 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
invasive disease-free survival (IDFS) after breast-conserving surgery
non-inferiority question
5 years
Study Arms (4)
no axillary surgery
EXPERIMENTALsentinel lymph node biopsy
ACTIVE COMPARATORstandard arm in first randomization
sentinel lymph node biopsy alone
EXPERIMENTALcompletion axillary lymph node dissection
ACTIVE COMPARATORstandard arm in second randomization
Interventions
in cases with newly diagnosed breast cancer and clinically negative axillary status
in cases with 1-3 macrometastases in sentinel lymph nodes
Eligibility Criteria
You may qualify if:
- Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements
- Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned
- Age at diagnosis at least 18 years
- Preoperative imaging techniques with estimated tumor size of \<5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status)
- 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 before randomization
- No clinical evidence for distant metastasis (M0)
- Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation)
You may not qualify if:
- History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix
- Time since core biopsy \>3 months (optimal \<1 month)
- Previous and already (neoadjuvant) treated invasive breast carcinoma
- Histologically non-invasive breast carcinoma
- cT3/T4 or iT3/T4 tumors
- pregnant or lactating patients
- Planned total mastectomy (e.g. multicentric tumors )
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GBG Forschungs GmbHcollaborator
- University of Rostocklead
- German Cancer Aidcollaborator
Study Sites (150)
Universitätsfrauenklinik Salzburg
Salzburg, State of Salzburg, 5020, Austria
BGZ Dornbirn, Gynäkologie
Dornbirn, 6850, Austria
LKH Uni-Klinikum Graz, Gynäkologie
Graz, 8036, Austria
Ordensklinikum-BHS
Linz, 4010, Austria
Kepler Universitätsklinikum
Linz, 4020, Austria
KH der Barmherzigen Brüder
Saint Veit/Glan, 9300, Austria
Hanusch-Krankenhaus, Brustzentrum
Vienna, 1140, Austria
Landes-Krankenhaus Wolfsberg, Chirurgie
Wolfsberg, 9400, Austria
Ostalb-Klinikum, Brustzentrum Aalen
Aalen, Baden-Wurttemberg, 73430, Germany
Caritas-Krankenhaus Brustzentrum Tauberfranken
Bad Mergentheim, Baden-Wurttemberg, 97980, Germany
Klinikum Mittelbach Brustzentrum
Baden-Baden, Baden-Wurttemberg, 76532, Germany
Sana-Klinikum Biberach
Biberach, Baden-Wurttemberg, 88400, Germany
Krankenhaus Bietigheim
Bietigheim, Baden-Wurttemberg, 74321, Germany
Klinikum Böblingen
Böblingen, Baden-Wurttemberg, 71032, Germany
Fürst-Stirum-Klinik
Bruchsal, Baden-Wurttemberg, 76646, Germany
Brustzentrum Donau-Riß
Ehingen, Baden-Wurttemberg, 89584, Germany
Klinikum Esslingen
Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany
Frauenklinik Freudenstadt
Freudenstadt, Baden-Wurttemberg, 72250, Germany
Universitätsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Städtisches Klinikum Karlsruhe
Karlsruhe, Baden-Wurttemberg, 76133, Germany
ViDia Christliche Kliniken, Diakonissenkrankenhaus Karlsruhe
Karlsruhe, Baden-Wurttemberg, 76199, Germany
St. Elisabethen Krankenhaus
Loerrach, Baden-Wurttemberg, 79539, Germany
Klinikum Ludwigsburg
Ludwigsburg, Baden-Wurttemberg, 71640, Germany
Helios Klinik Pforzheim
Pforzheim, Baden-Wurttemberg, 75175, Germany
Siloah St. Trudpert Klinikum
Pforzheim, Baden-Wurttemberg, 75179, Germany
Klinikum am Steinenberg
Reutlingen, Baden-Wurttemberg, 72764, Germany
Helios Klinik Rottweil
Rottweil, Baden-Wurttemberg, 78628, Germany
Rems-Murr Klinik
Schorndorf, Baden-Wurttemberg, 73614, Germany
Klinikum Tuttlingen
Tuttlingen, Baden-Wurttemberg, 78532, Germany
Universitätsfrauenklinik
Tübingen, Baden-Wurttemberg, 72076, Germany
Universitätsfrauenklinik Ulm
Ulm, Baden-Wurttemberg, 89075, Germany
Schwarzwald-Baar Klinikum
Villingen-Schwenningen, Baden-Wurttemberg, 78050, Germany
Rems-Murr Kliniken
Winnenden, Baden-Wurttemberg, 71364, Germany
Klinikum St. Marien
Amberg, Bavaria, 92224, Germany
AN regiomed Klinikum Ansbach
Ansbach, Bavaria, 91522, Germany
Klinikum Aschaffenburg
Aschaffenburg, Bavaria, 63739, Germany
Hämatologisch-onkologische Praxis
Augsburg, Bavaria, 86150, Germany
Klinikum Bayreuth GmbH, Frauenklinik
Bayreuth, Bavaria, 95445, Germany
Kreisklinik Ebersberg
Ebersberg, Bavaria, 85560, Germany
Gynäkologische Praxis
Eggenfelden, Bavaria, 84307, Germany
Klinikum Fürth
Fürth, Bavaria, 90766, Germany
Klinikum Kempten-Oberallgäu
Kempten (Allgäu), Bavaria, 87439, Germany
Klinikum Landshut
Landshut, Bavaria, 84034, Germany
Klinikum Fichtelgebirge gGmbH, Brustzentrum
Marktredwitz, Bavaria, 95615, Germany
Klinikum Memmingen
Memmingen, Bavaria, 87700, Germany
Klinikum der Universität München
München, Bavaria, 80337, Germany
Klinikum Harlaching, Frauenklinik
München, Bavaria, 81545, Germany
Klinikum Passau
Passau, Bavaria, 94032, Germany
Frauenklinik der Universität Regensburg, Caritas-Krankenhaus St. Josef
Regensburg, Bavaria, 93053, Germany
Klinikum Starnberg
Starnberg, Bavaria, 82319, Germany
Klinikum Traunstein
Traunstein, Bavaria, 83278, Germany
Kliniken Nordoberpfalz AG, Brustzentrum Weiden
Weiden, Bavaria, 92637, Germany
Rotkreuzklinik Würzburg
Würzburg, Bavaria, 97070, Germany
Klinikum Mitte, Missio Brustzentrum
Würzburg, Bavaria, 97074, Germany
Städtisches Klinikum Brandenburg
Brandenburg an der Havel, Brandenburg, 14770, Germany
Carl-Thiem-Klinikum
Cottbus, Brandenburg, 03046, Germany
Ev. Krankenhaus, Frauenklinik
Ludwigsfelde, Brandenburg, 14974, Germany
Klinikum Ernst von Bergmann
Potsdam, Brandenburg, 14467, Germany
Universitätsklinikum Hamburg, Brustzentrum
Hamburg, Free and Hanseatic City of Hamburg, 20246, Germany
Agaplesion Diakonieklinikum, Brustzentrum
Hamburg, Free and Hanseatic City of Hamburg, 20259, Germany
Gynäkologische Praxisklinik Harburg
Hamburg, Free and Hanseatic City of Hamburg, 21673, Germany
Albertinen-Krankenhaus, Brustzentrum
Hamburg, Free and Hanseatic City of Hamburg, 22457, Germany
St. Joseph Stift
Bremen, Free Hanseatic City of Bremen, 28209, Germany
DIAKO Krankenhaus Bremen
Bremen, Free Hanseatic City of Bremen, 28239, Germany
Agaplesion Markus Krankenhaus
Frankfurt am Main, Hesse, 60431, Germany
Universitätsklinikum Brustzentrum
Frankfurt am Main, Hesse, 60590, Germany
Klinikum Frankfurt Höchst
Frankfurt am Main, Hesse, 65929, Germany
Main-Kinzig-Kliniken Gelnhausen
Gelnhausen, Hesse, 63571, Germany
Klinikum Hanau GmbH
Hanau, Hesse, 63450, Germany
Kreiskrankenhaus Bergstraße gGmbH
Heppenheim an der Bergstrasse, Hesse, 64646, Germany
Elisabeth Krankenhaus Kassel
Kassel, Hesse, 34117, Germany
Klinikum Kassel
Kassel, Hesse, 34125, Germany
Sana Klinikum Offenbach
Offenbach, Hesse, 63069, Germany
St. Josefs-Hospital, Frauenklinik
Wiesbaden, Hesse, 65189, Germany
Asklepios Paulinenklinik
Wiesbaden, Hesse, 65197, Germany
Helios Dr. Horst Schmidt Klinikum
Wiesbaden, Hesse, 65199, Germany
AKH Celle, Brustzentrum
Celle, Lower Saxony, 29223, Germany
Franziskus Hospital Harderberg
Georgsmarienhütte, Lower Saxony, 49124, Germany
Helios Klinikum Gifhorn
Gifhorn, Lower Saxony, 38518, Germany
Henriettenstiftung Frauenklinik
Hanover, Lower Saxony, 30559, Germany
Vinzenzkrankenhaus Hannover
Hanover, Lower Saxony, 30559, Germany
MHH Frauenklinik
Hanover, Lower Saxony, 30625, Germany
St. Bernward Krankenhaus
Hildesheim, Lower Saxony, 31134, Germany
Bonifatius-Hospital, Brustzentrum
Lingen, Lower Saxony, 49808, Germany
Euregio-Klinik Brustzentrum Nordhorn
Nordhorn, Lower Saxony, 48527, Germany
Agaplesion Ev. Klinikum, Brustzentrum Schaumburg
Obernkirchen, Lower Saxony, 31683, Germany
Klinikum Osnabrück
Osnabrück, Lower Saxony, 49076, Germany
Diakoniekrankenhaus, Frauenklinik
Rotenburg (Wümme), Lower Saxony, 27356, Germany
Klinikum Wolfsburg, Frauenklinik
Wolfsburg, Lower Saxony, 38440, Germany
Universität Greifswald, Frauenklinik
Greifswald, Mecklenburg-Vorpommern, 17475, Germany
Dietrich Bonhoeffer Klinikum, Brustzentrum
Neubrandenburg, Mecklenburg-Vorpommern, 17036, Germany
Universitäts-Frauenklinik
Rostock, Mecklenburg-Vorpommern, 18059, Germany
Helios Kliniken Schwerin
Schwerin, Mecklenburg-Vorpommern, 19049, Germany
Augusta-Klinik
Bochum, Nordrhein, 44791, Germany
Universitätsfrauenklinik Bonn
Bonn, Nordrhein, 53105, Germany
Marienhospital Bottrop
Bottrop, Nordrhein, 46236, Germany
Uniklinik Köln
Cologne, Nordrhein, 50931, Germany
St. Elisabeth Krankenhaus, Brustzentrum
Cologne, Nordrhein, 50935, Germany
Frauenklinik der H.-Heine-Universität
Düsseldorf, Nordrhein, 40225, Germany
Universitätsklinikum Essen Frauenklinik
Essen, Nordrhein, 45122, Germany
Kliniken Essen-Mitte
Essen, Nordrhein, 45136, Germany
Klinikum Märkische Kliniken, Brustzentrum
Lüdenscheid, Nordrhein, 58515, Germany
Klinikum Lünen, Brustzentrum
Lünen, Nordrhein, 44534, Germany
St. Franziskus-Hospital
Münster, Nordrhein, 48145, Germany
Universitätsklinikum Münster
Münster, Nordrhein, 48149, Germany
Marienkrankenhaus
Schwerte, Nordrhein, 58239, Germany
St. Marienkrankenhaus, Frauenklinik
Siegen, Nordrhein, 57072, Germany
St. Josef-Hospital, BZ Rhein-Sieg
Troisdorf, Nordrhein, 53840, Germany
Katharinen-Hospital, Brustzentrum
Unna, Nordrhein, 59423, Germany
Marien-Hospital
Wesel, Nordrhein, 46483, Germany
Westpfalz Klinikum
Kaiserslautern, Rhineland-Palatinate, 67655, Germany
BZ Mittelrhein Koblenz+Mayen
Koblenz, Rhineland-Palatinate, 56073, Germany
Klinikum Ludwigshafen
Ludwigshafen am Rhein, Rhineland-Palatinate, 67063, Germany
Diakonissen-Stiftungs-Krankenhaus Speyer
Speyer, Rhineland-Palatinate, 67346, Germany
Stadtkrankenhaus Worms
Worms, Rhineland-Palatinate, 67550, Germany
Brustzentrum Nordsachsen
Borna, Saxony, 04552, Germany
Diakonissenkrankenhaus
Dresden, Saxony, 01099, Germany
Krankenhaus St. Joseph-Stift
Dresden, Saxony, 01307, Germany
Universität Dresden, Frauenklinik
Dresden, Saxony, 01307, Germany
Städtisches Klinikum
Görlitz, Saxony, 02828, Germany
Universitätsklinikum Leipzig, Brustzentrum
Leipzig, Saxony, 04103, Germany
St. Elisabeth Krankenhaus
Leipzig, Saxony, 04277, Germany
Klinikum Obergöltzsch Rodewisch
Rodewisch, Saxony, 08228, Germany
Helios Klinik
Schkeuditz, Saxony, 04435, Germany
Krankenhaus St. Elisabeth und St. Barbara
Halle, Saxony-Anhalt, 06110, Germany
Universität Halle/Saale, Frauenklinik
Halle, Saxony-Anhalt, 06120, Germany
Altmark-Klinikum Brustzentrum
Hansestadt Salzwedel, Saxony-Anhalt, 29410, Germany
Klinik St. Marienstift
Magdeburg, Saxony-Anhalt, 39110, Germany
Johanniter-Krankenhaus, Frauenklinik
Stendal, Saxony-Anhalt, 39576, Germany
Harzklinikum, Brustzentrum Harz
Wernigerode, Saxony-Anhalt, 38855, Germany
Sana-Klinik
Eutin, Schleswig-Holstein, 23701, Germany
DIAKO Diakonissenkrankenhaus
Flensburg, Schleswig-Holstein, 24939, Germany
Universitätsklinikum Schleswig-Hostein
Kiel, Schleswig-Holstein, 24105, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
Lübeck, Schleswig-Holstein, 23538, Germany
Charite Campus Mitte
Berlin, State of Berlin, 10117, Germany
Sana Klinikum Berlin-Lichtenberg
Berlin, State of Berlin, 10365, Germany
St. Gertrauden Krankenhaus
Berlin, State of Berlin, 10713, Germany
DRK Kliniken Köpenick
Berlin, State of Berlin, 12559, Germany
Park-Klinik Weißensee
Berlin, State of Berlin, 13086, Germany
Evang. Waldkrankenhaus Spandau
Berlin, State of Berlin, 13589, Germany
DRK-Kliniken Westend
Berlin, State of Berlin, 14050, Germany
Krankenhaus Waldfriede
Berlin, State of Berlin, 14163, Germany
Helios Klinikum, Klinik für Gynäkologie
Buch, State of Berlin, 13125, Germany
Hufeland-Klinik Bad Langensalza
Bad Langensalza, Thuringia, 99947, Germany
SRH Waldklinikum
Gera, Thuringia, 07548, Germany
Universitätsklinikum Jena
Jena, Thuringia, 07747, Germany
Helios Klinikum Meiningen, Brustzentrum
Meiningen, Thuringia, 98617, Germany
DRK Krankenhaus, Brustzentrum
Sömmerda, Thuringia, 99610, Germany
SRH Zentralklinikum Suhl
Suhl, Thuringia, 98527, Germany
Related Publications (6)
Reimer T, Stachs A, Nekljudova V, Loibl S, Hartmann S, Wolter K, Hildebrandt G, Gerber B. Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1-2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial. Geburtshilfe Frauenheilkd. 2017 Feb;77(2):149-157. doi: 10.1055/s-0042-122853.
PMID: 28331237RESULTHildebrandt G, Stachs A, Gerber B, Potenberg J, Krug D, Wolter K, Kuhn T, Zierhut D, Sedlmayer F, Kaiser J, Reitsamer R, Heil J, Nekljudova V, Bekes I, Loibl S, Reimer T. Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):683-693. doi: 10.1016/j.ijrobp.2020.04.042. Epub 2020 May 11.
PMID: 32437921RESULTReimer T, Stachs A, Veselinovic K, Polata S, Muller T, Kuhn T, Heil J, Ataseven B, Reitsamer R, Hildebrandt G, Knauer M, Golatta M, Stefek A, Zahm DM, Thill M, Nekljudova V, Krug D, Loibl S, Gerber B; INSEMA investigators. Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer. EClinicalMedicine. 2022 Nov 25;55:101756. doi: 10.1016/j.eclinm.2022.101756. eCollection 2023 Jan.
PMID: 36457648RESULTMarme F, Krieghoff-Henning E, Gerber B, Schmitt M, Zahm DM, Bauerschlag D, Forstbauer H, Hildebrandt G, Ataseven B, Brodkorb T, Denkert C, Stachs A, Krug D, Heil J, Golatta M, Kuhn T, Nekljudova V, Gaiser T, Schonmehl R, Brochhausen C, Loibl S, Reimer T, Brinker TJ. Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images. Eur J Cancer. 2023 Dec;195:113390. doi: 10.1016/j.ejca.2023.113390. Epub 2023 Oct 18.
PMID: 37890350RESULTReimer T, Stachs A, Veselinovic K, Kuhn T, Heil J, Polata S, Marme F, Muller T, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Zahm DM, Thill M, Golatta M, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025 Mar 13;392(11):1051-1064. doi: 10.1056/NEJMoa2412063. Epub 2024 Dec 12.
PMID: 39665649RESULTReimer T, Stachs A, Veselinovic K, Kuehn T, Heil J, Polata S, Marme F, Trapp E, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Stahl N, Thill M, Strittmatter HJ, Mueller T, Golatta M, Zahm DM, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary surgery in patients with sentinel node macrometastases: secondary results of the randomized INSEMA trial. NPJ Breast Cancer. 2026 Jan 27;12(1):19. doi: 10.1038/s41523-026-00902-7.
PMID: 41593108DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Toralf Reimer, MD, PhD
University Medical Center Rostock
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof. Dr. Toralf Reimer
Study Record Dates
First Submitted
June 4, 2015
First Posted
June 9, 2015
Study Start
September 1, 2015
Primary Completion
August 30, 2024
Study Completion (Estimated)
December 1, 2029
Last Updated
May 1, 2026
Record last verified: 2026-04