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

Montagna, G.; Laws, A.; Ferrucci, M.; Mrdutt, M. M.; Sun, S. X.; Bademler, S.; Balbaloglu, H.; Balint-Lahat, N.; Banys-Paluchowski, M.; Barrio, A. V.; Benson, J.; Bese, N.; Boughey, J. C.; Boyle, M. K.; Diego, E. J.; Eden, C.; Eller, R.; Goldschmidt, M.; Hlavin, C.; Heidinger, M.; Jelinska, J.; Karadeniz Cakmak, G.; Kesmodel, S. B.; King, T. A.; Kuerer, H. M.; Loesch, J.; Milardi, F.; Murawa, D.; Moo, T. -A.; Menes, T. S.; Passeri, D.; Pastoriza, J. M.; Perhavec, A.; Pislar, N.; Polidorio, N.; Rami, A.; Ryu, J. M.; Schulz, A.; Sevilimedu, V.; Ugurlu, M. U.; Uras, C.; Van Hemert, A.; Wong, S. M.; Yoo, T. -K. R.; Zhang, J. Q.; Karanlik, H.; Cabioglu, N.; Peeters, M. -J. V.; Morrow, M.; Weber, W. P.; Gentile, D.; Gentilini, O. D.

doi:10.1200/JCO.24.01052

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+).

Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study / Montagna, G.; Laws, A.; Ferrucci, M.; Mrdutt, M. M.; Sun, S. X.; Bademler, S.; Balbaloglu, H.; Balint-Lahat, N.; Banys-Paluchowski, M.; Barrio, A. V.; Benson, J.; Bese, N.; Boughey, J. C.; Boyle, M. K.; Diego, E. J.; Eden, C.; Eller, R.; Goldschmidt, M.; Hlavin, C.; Heidinger, M.; Jelinska, J.; Karadeniz Cakmak, G.; Kesmodel, S. B.; King, T. A.; Kuerer, H. M.; Loesch, J.; Milardi, F.; Murawa, D.; Moo, T. -A.; Menes, T. S.; Passeri, D.; Pastoriza, J. M.; Perhavec, A.; Pislar, N.; Polidorio, N.; Rami, A.; Ryu, J. M.; Schulz, A.; Sevilimedu, V.; Ugurlu, M. U.; Uras, C.; Van Hemert, A.; Wong, S. M.; Yoo, T. -K. R.; Zhang, J. Q.; Karanlik, H.; Cabioglu, N.; Peeters, M. -J. V.; Morrow, M.; Weber, W. P.; Gentile, D.; Gentilini, O. D.. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - 43:7(2025), pp. 810-820. [10.1200/JCO.24.01052]