Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study

G Giacomo Montagna (Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY) A Alison Laws (Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA) M Massimo Ferrucci (Breast Surgical Unit, Veneto Institute of Oncology IRCCS, Padova, Veneto, Italy) M Mary M. Mrdutt (Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN) S Susie X. Sun (Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX) S Suleyman Bademler (Institute of Oncology, Istanbul University, Istanbul, Turkey) H Hakan Balbaloglu (Department of General Surgery, School of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Turkey) N Nora Balint-Lahat (Sheba Medical Center, Ramat Gan, Israel) M Maggie Banys-Paluchowski A Andrea V. Barrio (Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY) J John Benson (Mayo Clinic, Rochester, Minnesota, United States) N Nuran Bese (Research Institute of Senology Acibadem, Istanbul, Turkey) J Judy C. Boughey (Matthew P. Goetz, MD and Grace M. Choong, MD, Department of Oncology, Mayo Clinic, Rochester, MN; Tanya L. Hoskin, MS, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN; Judy C. Boughey, MD, Division of Breast and Melanoma Surgical Oncology, Mayo Clinic, Rochester, MN; Sameera R. Wijayawardana, PhD, Eli Lilly and Company, Indianapolis, IN; and James N. Ingle, MD, Department of Oncology, Mayo Clinic, Rochester, MN) M Marissa K. Boyle (Cedars-Sinai Medical Center, Los Angeles, CA) E Emilia J. Diego (University of Pittsburgh Medical Center, Pittsburgh, PA) C Claire Eden (Department of Surgery, New York-Presbyterian/Weill Cornell Medical Center, New York, NY) R Ruth Eller (University of Basel, Basel, Switzerland) M Maite Goldschmidt (University of Basel, Basel, Switzerland) C Callie Hlavin (University of Pittsburgh Medical Center, Pittsburgh, PA) M Martin Heidinger (University Hospital Basel and Faculty of Medicine University of Basel, Basel, Switzerland) J Justyna Jelinska (General Surgery and Surgical Oncology Clinic, Collegium Medicum, University Zielona Gora, Zielona Góra, Poland) G Guldeniz Karadeniz Cakmak (Zonguldak BEUN The School of Medicine, Breast and Endocrine Unit, General Surgery Department, Kozlu/Zonguldak, Turkey) S Susan B. Kesmodel (DeWitt Daughtry Department of Surgery, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL) T Tari A. King (Winship Cancer Institute, Atlanta, GA) H Henry M. Kuerer (Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX) J Julie Loesch (University of Basel, Basel, Switzerland) F Francesco Milardi (General Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy) D Dawid Murawa (General Surgery and Surgical Oncology Department, Collegium Medicum, University in Zielona Gora, Zielona Gora, Poland) T Tracy-Ann Moo (Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY) T Tehillah S. Menes (Sheba Medical Center, Tel Hashomer, Israel) D Daniele Passeri J Jessica M. Pastoriza (Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, New York, NY) A Andraz Perhavec (Institute of Oncology Ljubljana, Ljubljana, Slovenia) N Nina Pislar (Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia) N Natalia Polidorio A Avina Rami (Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA) J Jai Min Ryu (Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea) A Alexandra Schulz (University Hospital Basel, Basel, Switzerland) V Varadan Sevilimedu (Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY) M M. Umit Ugurlu (Marmara University School of Medicine, Istanbul, Turkey) C Cihan Uras (Research Institute of Senology Acibadem, Istanbul, Turkey) A Annemiek van Hemert (Department of Surgery, Stichting HET Netherlands Kanker Instituut-Antoni van Leeuwenhoek, Amsterdam, the Netherlands) S Stephanie M. Wong (Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Canada) T Tae-Kyung Robyn Yoo (Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea) J Jennifer Q. Zhang (Division of Breast Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) H Hasan Karanlik (Institute of Oncology, Istanbul University, Istanbul, Turkey) N Neslihan Cabioglu (Istanbul University Faculty of Medicine, Department of Surgery, Istanbul, Turkey) M Marie-Jeanne Vrancken Peeters (Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands) M Monica Morrow (Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York) W Walter P. Weber S Sung Gwe Ahn M Mariacarla Andreozzi D Daniel Meirelles Barbalho J Jean François Boileau E Edi Brogi F Flavia Vidal Cabero (CORA - Centro Avançado de Diagnóstico da Mama do Hospital das Clinicas da Universidade Federal de Goias, Goiania, Goias, Brazil) D Daniela Cocco F Fabio Corsi A Angelena Crown E Eelco de Bree M Maria del Mar Vernet-Tomas C Christine Deutschmann N Nina Ditsch E Emanuela Esposito O Oluwadamilola M. Fayanju F Franziska Fick (Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany) F Florian Fitzal (Department of General Surgery and Breast Health Center, Hanusch Hospital, Vienna, Austria) M Meghan R. Flanagan D Damiano Gentile (Humanitas University - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy) O Oreste D. Gentilini (Breast Surgery Unit, IRCCS Ospedale San Raffaele, Milan, Italy) A Anne Grabenstetter M Mehmet Ali Gulcelik J Jörg Heil (University Hospital Heidelberg, Heidelberg, Germany) J Johannes Holtschmidt (German Breast Group, Neu-Isenburg, Germany) N Natalia Krawczyk (Department of Gynecology and Obstetrics, University Hospital Düsseldorf, Düsseldorf, Germany) T Thorsten Kühn (Hospital Esslingen, Esslingen, Germany) S Sherko Kümmel C Cornelia Leo M Mahmut Muslumanoglu V Valentina Nekljudova (German Breast Group, Neu-Isenburg, Germany) L Lisa A. Newman M Melissa L. Pilewskie F Fiorita Poulakaki (Breast Surgery Department, Athens Medical Centre, Athens, Greece) F Fabian Riedel (Department of Obstetrics and Gynecology, Heidelberg University Hospital, Heidelberg, Germany) N Nicola Rocco F Freya R. Schnabel C Christopher Schwartz (Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY) E Emily L. Siegel (Department of Surgery, University of Southern California, Los Angeles, CA) C Colin Simonson C Christian Singer L Leonardo Ribeiro Soares (CORA - Advanced Center for Diagnosis of Breast Cancer, Federal University of Goias, Goiania, Goias, Brazil) E Ekaterini Christina Tampaki A Athanasios Tampakis M Marios Konstantinos Tasoulis C Christoph Tausch C Cicero Urban (Nossa Senhora das Graças Hospital and Centro de Doenças da Mama Oncoplastic Academy, Curitiba, Brazil) A Astrid Botty Van den Bruele G Glenn Vergauwen D Denise Vorburger F Fredrik Wärnberg A Anna Weiss A Austin D. Williams (Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA) K Kerstin Wimmer S Steven G. Woodward F Firdos M. Ziauddin

Abstract

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

Article Details

Volume / Issue Vol. 43, Issue 7
Published March 01, 2025
Pages 810-820
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (105)

G

Giacomo Montagna

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

A

Alison Laws

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA

M

Massimo Ferrucci

Breast Surgical Unit, Veneto Institute of Oncology IRCCS, Padova, Veneto, Italy

M

Mary M. Mrdutt

Division of Breast and Melanoma Surgical Oncology, Department of Surgery, Mayo Clinic, Rochester, MN

S

Susie X. Sun

Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

S

Suleyman Bademler

Institute of Oncology, Istanbul University, Istanbul, Turkey

H

Hakan Balbaloglu

Department of General Surgery, School of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Turkey

N

Nora Balint-Lahat

Sheba Medical Center, Ramat Gan, Israel

M

Maggie Banys-Paluchowski

A

Andrea V. Barrio

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

J

John Benson

Mayo Clinic, Rochester, Minnesota, United States

N

Nuran Bese

Research Institute of Senology Acibadem, Istanbul, Turkey

J

Judy C. Boughey

Matthew P. Goetz, MD and Grace M. Choong, MD, Department of Oncology, Mayo Clinic, Rochester, MN; Tanya L. Hoskin, MS, Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, MN; Judy C. Boughey, MD, Division of Breast and Melanoma Surgical Oncology, Mayo Clinic, Rochester, MN; Sameera R. Wijayawardana, PhD, Eli Lilly and Company, Indianapolis, IN; and James N. Ingle, MD, Department of Oncology, Mayo Clinic, Rochester, MN

M

Marissa K. Boyle

Cedars-Sinai Medical Center, Los Angeles, CA

E

Emilia J. Diego

University of Pittsburgh Medical Center, Pittsburgh, PA

C

Claire Eden

Department of Surgery, New York-Presbyterian/Weill Cornell Medical Center, New York, NY

R

Ruth Eller

University of Basel, Basel, Switzerland

M

Maite Goldschmidt

University of Basel, Basel, Switzerland

C

Callie Hlavin

University of Pittsburgh Medical Center, Pittsburgh, PA

M

Martin Heidinger

University Hospital Basel and Faculty of Medicine University of Basel, Basel, Switzerland

J

Justyna Jelinska

General Surgery and Surgical Oncology Clinic, Collegium Medicum, University Zielona Gora, Zielona Góra, Poland

G

Guldeniz Karadeniz Cakmak

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

S

Susan B. Kesmodel

DeWitt Daughtry Department of Surgery, University of Miami/Sylvester Comprehensive Cancer Center, Miami, FL

T

Tari A. King

Winship Cancer Institute, Atlanta, GA

H

Henry M. Kuerer

Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX

J

Julie Loesch

University of Basel, Basel, Switzerland

F

Francesco Milardi

General Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy

D

Dawid Murawa

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

T

Tracy-Ann Moo

Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY

T

Tehillah S. Menes

Sheba Medical Center, Tel Hashomer, Israel

D

Daniele Passeri

J

Jessica M. Pastoriza

Breast Surgery Division, Department of Surgery, Montefiore Medical Center, Montefiore Einstein Center for Cancer Care, New York, NY

A

Andraz Perhavec

Institute of Oncology Ljubljana, Ljubljana, Slovenia

N

Nina Pislar

Department of Surgical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia

N

Natalia Polidorio

A

Avina Rami

Division of Breast Surgery, Department of Surgery, Brigham and Women's Hospital, Boston, MA

J

Jai Min Ryu

Division of Breast Surgery, Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

A

Alexandra Schulz

University Hospital Basel, Basel, Switzerland

V

Varadan Sevilimedu

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY

M

M. Umit Ugurlu

Marmara University School of Medicine, Istanbul, Turkey

C

Cihan Uras

Research Institute of Senology Acibadem, Istanbul, Turkey

A

Annemiek van Hemert

Department of Surgery, Stichting HET Netherlands Kanker Instituut-Antoni van Leeuwenhoek, Amsterdam, the Netherlands

S

Stephanie M. Wong

Stroll Cancer Prevention Centre, Jewish General Hospital, and McGill University Medical School, Montreal, Canada

T

Tae-Kyung Robyn Yoo

Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea

J

Jennifer Q. Zhang

Division of Breast Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

H

Hasan Karanlik

Institute of Oncology, Istanbul University, Istanbul, Turkey

N

Neslihan Cabioglu

Istanbul University Faculty of Medicine, Department of Surgery, Istanbul, Turkey

M

Marie-Jeanne Vrancken Peeters

Department of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands

M

Monica Morrow

Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York

W

Walter P. Weber

S

Sung Gwe Ahn

M

Mariacarla Andreozzi

D

Daniel Meirelles Barbalho

J

Jean François Boileau

E

Edi Brogi

F

Flavia Vidal Cabero

CORA - Centro Avançado de Diagnóstico da Mama do Hospital das Clinicas da Universidade Federal de Goias, Goiania, Goias, Brazil

D

Daniela Cocco

F

Fabio Corsi

A

Angelena Crown

E

Eelco de Bree

M

Maria del Mar Vernet-Tomas

C

Christine Deutschmann

N

Nina Ditsch

E

Emanuela Esposito

O

Oluwadamilola M. Fayanju

F

Franziska Fick

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

F

Florian Fitzal

Department of General Surgery and Breast Health Center, Hanusch Hospital, Vienna, Austria

M

Meghan R. Flanagan

D

Damiano Gentile

Humanitas University - IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

O

Oreste D. Gentilini

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

A

Anne Grabenstetter

M

Mehmet Ali Gulcelik

J

Jörg Heil

University Hospital Heidelberg, Heidelberg, Germany

J

Johannes Holtschmidt

German Breast Group, Neu-Isenburg, Germany

N

Natalia Krawczyk

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

T

Thorsten Kühn

Hospital Esslingen, Esslingen, Germany

S

Sherko Kümmel

C

Cornelia Leo

M

Mahmut Muslumanoglu

V

Valentina Nekljudova

German Breast Group, Neu-Isenburg, Germany

L

Lisa A. Newman

M

Melissa L. Pilewskie

F

Fiorita Poulakaki

Breast Surgery Department, Athens Medical Centre, Athens, Greece

F

Fabian Riedel

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

N

Nicola Rocco

F

Freya R. Schnabel

C

Christopher Schwartz

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

E

Emily L. Siegel

Department of Surgery, University of Southern California, Los Angeles, CA

C

Colin Simonson

C

Christian Singer

L

Leonardo Ribeiro Soares

CORA - Advanced Center for Diagnosis of Breast Cancer, Federal University of Goias, Goiania, Goias, Brazil

E

Ekaterini Christina Tampaki

A

Athanasios Tampakis

M

Marios Konstantinos Tasoulis

C

Christoph Tausch

C

Cicero Urban

Nossa Senhora das Graças Hospital and Centro de Doenças da Mama Oncoplastic Academy, Curitiba, Brazil

A

Astrid Botty Van den Bruele

G

Glenn Vergauwen

D

Denise Vorburger

F

Fredrik Wärnberg

A

Anna Weiss

A

Austin D. Williams

Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA

K

Kerstin Wimmer

S

Steven G. Woodward

F

Firdos M. Ziauddin