Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study
Giacomo Montagna, Alison Laws, Massimo Ferrucci, Mary M. Mrdutt, Susie X. Sun, Süleyman Bademler, Hakan Balbaloĝlu, Nora Balint‐Lahat, Maggie Banys-Paluchowski, Andrea V. Barrio, John R. Benson, Nuran Beşe, Judy C. Boughey, Marissa K. Srour, Emilia J. Diego, Claire Eden, Ruth S. Eller, Maite Goldschmidt, Callie Hlavin, Martin Heidinger, Justyna Jelinska, Güldeniz Karadeniz Çakmak, Susan B. Kesmodel, Tari A. King, Henry M. Kuerer, Julie M Loesch, Francesco Milardi, Dawid Murawa, Tracy‐Ann Moo, Tehillah S. Menes, Daniele Passeri, Jessica Pastoriza, Andraž Perhavec, Nina Pislar, Natália Polidorio, Avina Rami, Jai Min Ryu, Alexandra Schulz, Varadan Sevilimedu, Mustafa Ümit Uğurlu, Cihan Uras, Annemiek K. E. van Hemert, Stephanie M. Wong, Tae-Kyung Yoo, Jennifer Q. Zhang, Hasan Karanlık, Neslihan Cabıoğlu, Marie-Jeanne T. F. D. Vrancken Peeters, Monica Morrow, William P. Weber, on behalf of the ICARO Study Group, Sung Gwe Ahn, Mariacarla Andreozzi, Daniel Meirelles Barbalho, J.-F. Boileau, Edi Brogi, Flávia Vidal Cabero, Daniela Cocco, Fabio Corsi, Angelena Crown, Eelco de Bree, M. Vernet-Tomás, Christine Deutschmann, Nina Ditsch, Emanuela Esposito, Oluwadamilola M. Fayanju, Franziska Fick, Florian Fitzal, Meghan R. Flanagan, Damiano Gentile, Oreste Gentilini, Anne Grabenstetter, Mehmet Ali Gülçelik, Jörg Heil, Johannes Holtschmidt, Natalia Krawczyk, Thorsten Kühn, Sherko Kümmel, Cornelia Leo, Mahmut Muslumanoglu, Valentina Nekljudova, Lisa A. Newman, Melissa Pilewskie, Fiorita Poulakaki, Fabian Riedel, Nicola Rocco, Freya Schnabel, Christopher J. Schwartz, Emily Siegel, Colin Simonson, Christian F. Singer, Leonardo Ribeiro Soares, Ekaterini Christina Tampaki, Athanasios Tampakis, Marios Konstantinos Tasoulis, Christoph Tausch, Cícero Úrban, Astrid Botty van den Bruele, Glenn Vergauwen, Denise Vorburger
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+).