Marking Techniques for Target Lymph Nodes in Node-Positive Breast Cancer Treated With Neoadjuvant Therapy in the AXSANA/EUBREAST-03/AGO-B-053 Study

M Maggie Banys-Paluchowski S Steffi Hartmann (Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany) J Jana de Boniface (Department of Surgery, Capio St. Göran’s Hospital, Stockholm) O Oreste D. Gentilini (Breast Surgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy) N Nina Ditsch E Elmar Stickeler (University Hospital Aachen, Aachen, Germany) G Guldeniz Karadeniz Cakmak (Zonguldak BEUN The School of Medicine, Breast and Endocrine Unit, General Surgery Department, Kozlu/Zonguldak, Turkey) M Michael Hauptmann (Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany) J Jennifer Schroth (Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany) M Marc Thill (Department of Gynecology and Gynecologic Oncology, Agaplesion Markus Hospital, Frankfurt am Main, Germany) R Rosa Di Micco (Breast Surgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy) M Markus Hahn (Department of Gynecology and Obstretrics, University Hospital Tübingen, Tübingen, Germany) D Dawid Murawa (General Surgery and Surgical Oncology Department, Collegium Medicum, University in Zielona Gora, Zielona Gora, Poland) I Isabel T. Rubio (Breast Surgical Unit, Clínica Universidad de Navarra, Madrid, Spain) D David Pinto (Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisboa, Portugal) M Michalis Kontos (Department of Surgery, University of Athens Laiko Hospital, Athens, Greece) L Laura Niinikoski M Maria Luisa Gasparri H Helidon Nina (Department of Surgery, Oncology Hospital, Tirana, Albania) L Lia P. Rebaza (Breast Surgery, Oncosalud, Lima, Peru) S Sarah Fröhlich (Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany) E Esther Schmidt (Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany) K Kristina Wihlfahrt (Practice for Gynecology and Obstetrics Wihlfahrt, Kiel, Germany) T Tomasz Berger (Department of Gynecology and Obstetrics, Müritz-Klinikum Waren, Waren, Germany) T Timo Basali (Department of Gynecology, Hospital Stuttgart, Stuttgart, Germany) F Franziska Ruf (Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Lübeck, Germany) A Angelika Rief (Department of Gynecology and Obstetrics, Medical University of Graz, Graz, Austria) E Eduard-Alexandru Bonci F Florentia Peintinger (Department of Gynecology and Obstetrics, Müritz-Klinikum Waren, Waren, Germany) E Ellen Schlichting (Department of Oncology, Oslo University Hospital, Norway) H Hagigat Valiyeva Qanimat (Oncologic Clinic of Azerbaijan Medical University, Baku, Azerbaijan) M Marian Vanhoeij (Universitair Ziekenhuis Brussel, Brussel, Belgium) G Geeta Kadayaprath (MAX Hospital, Patparganj, New Delhi, India) L Lukas Dostalek (Department of Obstetrics and Gynecology, Gynecologic Oncology Center, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic) A Ashutosh Kothari (Guy's & St. Thomas NHS Trust, Gillingham, United Kingdom) A Andraz Perhavec (Institute of Oncology Ljubljana, Ljubljana, Slovenia) T Tsvetomir Ivanov D Douglas Zippel (Surgical Oncology Unit Chaim Sheba Medical Centre, Ramat Gan, Israel) B Beata Adamczyk (Breast Cancer Unit, Greater Poland Cancer Centre, Poznan, Poland) M Mauro Porpiglia (Breast Unit S. Anna Hospital, Turin, Italy) G Günay M. Gürleyik (Department of General Surgery, Istanbul Haydarpasa Numune Training and Research Hospital, University of Health Sciences Turkey, İstanbul, Turkey) M Michael Untch (From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...) M Michael P. Lux (Department of Gynecology and Obstetrics, Frauenklinik St Louise, Paderborn, Frauenklinik St Josefs-Krankenhaus, Salzkotten, St Vincenz Kliniken, Paderborn, Germany) K Katharina Jursik (EUBREAST e.V., Esslingen, Germany) H Hans-Christian Kolberg T Toralf Reimer (Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany) N Nikolas Tauber (Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany) A Achim Rody (Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany) Z Zoltan Matrai (Department of Breast and Sarcoma Surgery, National Institute of Oncology, Budapest, Hungary) N Natalia Krawczyk (Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany) S Sarun Thongvitokomarn (Queen Sirikit Centre for Breast Cancer, Bangkok, Thailand) T Thorsten Kühn (Hospital Esslingen, Esslingen, Germany)

Abstract

PURPOSE Surgical axillary staging in patients with node-positive breast cancer (BC) who converted to clinical node negativity through neoadjuvant chemotherapy (NACT) has changed significantly in recent years. Targeted axillary dissection (TAD) and target lymph node (TLN) biopsy (TLNB) became increasingly popular. However, data comparing marking techniques for the TLN are limited. Here, we evaluate marking techniques in the largest prospective cohort worldwide. MATERIALS AND METHODS Among patients from the ongoing prospective multicenter AXSANA (EUBREAST-03) study who received TLN marking and TAD/TLNB, we evaluated different marking methods with respect to detection and removal rates and clinical performance. RESULTS Until January 6, 2025, 6,129 patients from 26 countries were enrolled. Of these patients, 2,596 had ≥1 TLN marked before NACT and completed surgery; 13.3% of the patients had ≥4 suspicious nodes at diagnosis. Pre-NACT TLN marking used a clip in 2,003 patients (77.2%), magnetic seed in 287 (11.1%), carbon ink in 192 (7.4%), radar marker in 119 (4.6%), radioactive seed in 18 (0.7%), radiofrequency identification device (RFID) in 12 (0.5%), or other methods in two (0.1%). One TLN was marked in 2,427 patients (93.5%), two TLNs in 138 (5.3%), and ≥3 in 27 patients (1%). Targeted removal of the TLN was planned in 2,100 patients (80.9%; TAD in 2,076 [80.0%] and TLNB in 24 [0.9%]). The TLN was detected and removed by TAD/TLNB in 1,915 patients (91.2%). TLN detection rate was the highest in patients whose TLNs were marked pre-NACT with markers suitable for probe-guided detection (96.6%; radioactive seed: 100%, magnetic seed: 96.9%, radar marker: 96.1%, RFID: 90%), followed by carbon ink (94.9%) and clip (89.6%; P < .001). CONCLUSION This large prospective analysis of patients with initially clinically node-positive BC receiving NACT demonstrates that probe-guided detection markers used to mark metastatic nodes before NACT provide superior detection rates.

Article Details

Volume / Issue Vol. 44, Issue 7
Published March 01, 2026
Pages 575-585
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (52)

M

Maggie Banys-Paluchowski

S

Steffi Hartmann

Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany

J

Jana de Boniface

Department of Surgery, Capio St. Göran’s Hospital, Stockholm

O

Oreste D. Gentilini

Breast Surgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy

N

Nina Ditsch

E

Elmar Stickeler

University Hospital Aachen, Aachen, Germany

G

Guldeniz Karadeniz Cakmak

Zonguldak BEUN The School of Medicine, Breast and Endocrine Unit, General Surgery Department, Kozlu/Zonguldak, Turkey

M

Michael Hauptmann

Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany

J

Jennifer Schroth

Institute of Biostatistics and Registry Research, Brandenburg Medical School Theodor Fontane, Neuruppin, Germany

M

Marc Thill

Department of Gynecology and Gynecologic Oncology, Agaplesion Markus Hospital, Frankfurt am Main, Germany

R

Rosa Di Micco

Breast Surgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy

M

Markus Hahn

Department of Gynecology and Obstretrics, University Hospital Tübingen, Tübingen, Germany

D

Dawid Murawa

General Surgery and Surgical Oncology Department, Collegium Medicum, University in Zielona Gora, Zielona Gora, Poland

I

Isabel T. Rubio

Breast Surgical Unit, Clínica Universidad de Navarra, Madrid, Spain

D

David Pinto

Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisboa, Portugal

M

Michalis Kontos

Department of Surgery, University of Athens Laiko Hospital, Athens, Greece

L

Laura Niinikoski

M

Maria Luisa Gasparri

H

Helidon Nina

Department of Surgery, Oncology Hospital, Tirana, Albania

L

Lia P. Rebaza

Breast Surgery, Oncosalud, Lima, Peru

S

Sarah Fröhlich

Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany

E

Esther Schmidt

Department of Gynecology and Obstetrics, University Hospital Rostock, Rostock, Germany

K

Kristina Wihlfahrt

Practice for Gynecology and Obstetrics Wihlfahrt, Kiel, Germany

T

Tomasz Berger

Department of Gynecology and Obstetrics, Müritz-Klinikum Waren, Waren, Germany

T

Timo Basali

Department of Gynecology, Hospital Stuttgart, Stuttgart, Germany

F

Franziska Ruf

Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Lübeck, Germany

A

Angelika Rief

Department of Gynecology and Obstetrics, Medical University of Graz, Graz, Austria

E

Eduard-Alexandru Bonci

F

Florentia Peintinger

Department of Gynecology and Obstetrics, Müritz-Klinikum Waren, Waren, Germany

E

Ellen Schlichting

Department of Oncology, Oslo University Hospital, Norway

H

Hagigat Valiyeva Qanimat

Oncologic Clinic of Azerbaijan Medical University, Baku, Azerbaijan

M

Marian Vanhoeij

Universitair Ziekenhuis Brussel, Brussel, Belgium

G

Geeta Kadayaprath

MAX Hospital, Patparganj, New Delhi, India

L

Lukas Dostalek

Department of Obstetrics and Gynecology, Gynecologic Oncology Center, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic

A

Ashutosh Kothari

Guy's & St. Thomas NHS Trust, Gillingham, United Kingdom

A

Andraz Perhavec

Institute of Oncology Ljubljana, Ljubljana, Slovenia

T

Tsvetomir Ivanov

D

Douglas Zippel

Surgical Oncology Unit Chaim Sheba Medical Centre, Ramat Gan, Israel

B

Beata Adamczyk

Breast Cancer Unit, Greater Poland Cancer Centre, Poznan, Poland

M

Mauro Porpiglia

Breast Unit S. Anna Hospital, Turin, Italy

G

Günay M. Gürleyik

Department of General Surgery, Istanbul Haydarpasa Numune Training and Research Hospital, University of Health Sciences Turkey, İstanbul, Turkey

M

Michael Untch

From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...

M

Michael P. Lux

Department of Gynecology and Obstetrics, Frauenklinik St Louise, Paderborn, Frauenklinik St Josefs-Krankenhaus, Salzkotten, St Vincenz Kliniken, Paderborn, Germany

K

Katharina Jursik

EUBREAST e.V., Esslingen, Germany

H

Hans-Christian Kolberg

T

Toralf Reimer

Department of Obstetrics and Gynecology, University of Rostock, Rostock, Germany

N

Nikolas Tauber

Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

A

Achim Rody

Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany

Z

Zoltan Matrai

Department of Breast and Sarcoma Surgery, National Institute of Oncology, Budapest, Hungary

N

Natalia Krawczyk

Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany

S

Sarun Thongvitokomarn

Queen Sirikit Centre for Breast Cancer, Bangkok, Thailand

T

Thorsten Kühn

Hospital Esslingen, Esslingen, Germany