Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study
Authors: Montagna Giacomo , Laws Alison , Ferrucci Massimo , Mrdutt Mary M. , Sun Susie X. , Bademler Suleyman , Balbaloglu Hakan , Balint-Lahat Nora , Banys-Paluchowski Maggie , Barrio Andrea V. , Benson John , Bese Nuran , Boughey Judy C. , Boyle Marissa K. , Diego Emilia J. , Eden Claire , Eller Ruth , Goldschmidt Maite , Hlavin Callie , Heidinger Martin , Jelinska Justyna , Karadeniz Cakmak Güldeniz , Kesmodel Susan B. , King Tari A. , Kuerer Henry M. , Loesch Julie , Milardi Francesco , Murawa Dawid , Moo Tracy-Ann , Menes Tehillah S. , Passeri Daniele , Pastoriza Jessica M. , Perhavec Andraz , Pislar Nina , Polidorio Natália , Rami Avina , Ryu Jai Min , Schulz Alexandra , Sevilimedu Varadan , Ugurlu M. Umit , Uras Cihan , van Hemert Annemiek , Wong Stephanie M. , Yoo Tae-Kyung Robyn , Zhang Jennifer Q. , Karanlik Hasan , Cabioğlu Neslihan , Peeters Marie-Jeanne Vrancken , Morrow Monica , Weber Walter P. ,   on behalf of the ICARO Study Group, Ahn Sung Gwe , Andreozzi Mariacarla , Barbalho Daniel Meirelles , Boileau Jean François , Brogi Edi , Cabero Flavia Vidal , Cocco Daniela , Corsi Fabio , Crown Angelena , de Bree Eelco , del Mar Vernet-Tomas Maria , Deutschmann Christine , Ditsch Nina , Esposito Emanuela , Fayanju Oluwadamilola M. , Fick Franziska , Fitzal Florian , Flanagan Meghan R. , Gentile Damiano , Gentilini Oreste D. , Grabenstetter Anne , Gulcelik Mehmet Ali , Heil Jörg , Holtschmidt Johannes , Krawczyk Natalia , Kühn Thorsten , Kümmel Sherko , Leo Cornelia , Muslumanoglu Mahmut , Nekljudova Valentina , Newman Lisa A. , Pilewskie Melissa L. , Poulakaki Fiorita , Riedel Fabian , Rocco Nicola , Schnabel Freya R. , Schwartz Christopher , Siegel Emily L. , Simonson Colin , Singer Christian , Soares Leonardo Ribeiro , Christina Tampaki Ekaterini , Tampakis Athanasios , Tasoulis Marios Konstantinos , Tausch Christoph , Urban Cicero , Van den Bruele Astrid Botty , Vergauwen Glenn , Vorburger Denise , Wärnberg Fredrik , Weiss Anna , Williams Austin D. , Wimmer Kerstin , Woodward Steven G. , Ziauddin Firdos M. 
Published: November 2024

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+).