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Observational Study
. 2025 Mar;43(7):810-820.
doi: 10.1200/JCO.24.01052. Epub 2024 Nov 7.

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

Giacomo Montagna  1 , Alison Laws  2 , Massimo Ferrucci  3 , Mary M Mrdutt  4 , Susie X Sun  5 , Suleyman Bademler  6 , Hakan Balbaloglu  7 , Nora Balint-Lahat  8   9 , Maggie Banys-Paluchowski  10 , Andrea V Barrio  1 , John Benson  11 , Nuran Bese  12 , Judy C Boughey  4 , Marissa K Boyle  13 , Emilia J Diego  14 , Claire Eden  15 , Ruth Eller  16   17 , Maite Goldschmidt  16   17 , Callie Hlavin  14 , Martin Heidinger  16   17 , Justyna Jelinska  18 , Güldeniz Karadeniz Cakmak  7 , Susan B Kesmodel  19 , Tari A King  2 , Henry M Kuerer  5 , Julie Loesch  16   17 , Francesco Milardi  3 , Dawid Murawa  18 , Tracy-Ann Moo  1 , Tehillah S Menes  8   9 , Daniele Passeri  3 , Jessica M Pastoriza  20 , Andraz Perhavec  21 , Nina Pislar  21 , Natália Polidorio  1 , Avina Rami  2 , Jai Min Ryu  22 , Alexandra Schulz  16   23 , Varadan Sevilimedu  24 , M Umit Ugurlu  25 , Cihan Uras  12 , Annemiek van Hemert  26 , Stephanie M Wong  27 , Tae-Kyung Robyn Yoo  28 , Jennifer Q Zhang  29 , Hasan Karanlik  6 , Neslihan Cabioğlu  30 , Marie-Jeanne Vrancken Peeters  31 , Monica Morrow  1 , Walter P Weber  16   17 ; ICARO Study Group
Collaborators, Affiliations
Observational Study

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

Giacomo Montagna et al. J Clin Oncol. 2025 Mar.

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+).

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

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Mary M. Mrdutt

Research Funding: Integro Theranostics (Inst)

Maggie Banys-Paluchowski

Honoraria: Novartis/Pfizer, AstraZeneca/Daiichi Sankyo, Seagen, Sirius Medical, MSD, GlaxoSmithKline, Exact Sciences, Stemline Therapeutics, Roche, pfm medical, Lilly, Onkowissen, Eisai, Amgen, Samsung, Canon Medical System, Gilead Sciences, Syantra, Resitu, Pierre Fabre

Consulting or Advisory Role: Novartis/Pfizer, Lilly, GlaxoSmithKline, Amgen, Roche, pfm medical, Onkowissen, Seagen, AstraZeneca, Eisai, Samsung, Canon Medical System, MSD, Daiichi Sankyo, Gilead Sciences, Exact Sciences, Sirius Medical, Pierre Fabre

Speakers' Bureau: Novartis/Pfizer, Lilly, Seagen, Roche, pfm medical, Onkowissen, AstraZeneca, Eisai, Amgen, Samsung, Canon Medical System, MSD, GlaxoSmithKline, Daiichi Sankyo, Gilead Sciences, Sirius Medical, Pierre Fabre, Exact Sciences

Research Funding: Exact Sciences, Endomagnetics (Inst), Merit Medical Systems (Inst), Mammotome (Inst), Hologic, Sirius Medical

Travel, Accommodations, Expenses: Lilly, Pfizer, Daiichi Sankyo/Astra Zeneca

Andrea V. Barrio

Honoraria: Novartis

Judy C. Boughey

Honoraria: UpToDate, PeerView, PER

Consulting or Advisory Role: CairnSurgical, SymBioSis (Inst)

Research Funding: Lilly (Inst)

Patents, Royalties, Other Intellectual Property: Patent pending—Methods and Materials for Assessing Chemotherapy Responsiveness and Treating Cancer (Inst)

Travel, Accommodations, Expenses: Endomagnetics

Tari A. King

Honoraria: Exact Sciences, Presica

Consulting or Advisory Role: GE Healthcare

Travel, Accommodations, Expenses: Grupo Oncoclinicas

Henry M. Kuerer

Consulting or Advisory Role: Targeted Medical Education, Inc, Merck

Patents, Royalties, Other Intellectual Property: NEJM Group, McGraw-Hill Publishing

Tehillah S. Menes

Travel, Accommodations, Expenses: Pfizer (Inst)

Andraz Perhavec

Stock and Other Ownership Interests: Krka d.d

Honoraria: MSD Oncology

Natália Polidorio

Employment: Memorial Sloan-Kettering Cancer Center

Research Funding: NIH (Inst), CAPES-CNPq

Travel, Accommodations, Expenses: Memorial Sloan-Kettering Cancer Center

Jai Min Ryu

Honoraria: Intuitive Surgical

Research Funding: Medtronic, AstranZeneca, DCgen

Cihan Uras

Employment: Acibadem Healthcare Group

Leadership: Acibadem Healthcare Group

Stephanie M. Wong

Consulting or Advisory Role: AstraZeneca/Merck

Tae-Kyung Robyn Yoo

Stock and Other Ownership Interests: Genopeaks

Monica Morrow

Honoraria: Roche TCRC

Walter P. Weber

Honoraria: MSD

Research Funding: Agendia

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flow diagram. ALND, axillary lymph node dissection; ITC, isolated tumor cell; MARI, marking axillary lymph nodes with radioactive iodine seeds; NAC, neoadjuvant chemotherapy; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy; TAD, targeted axillary dissection.
FIG 2.
FIG 2.
Proportion of patients with additional positive LNs at ALND by (A) all patients undergoing ALND (n = 182); (B) stratified by clinical nodal status at presentation (cN0 [n = 30] v cN+ [n = 152]); and (C) cN2/3 patients (n = 57). ALND, axillary lymph node dissection; LN, lymph node.
FIG 3.
FIG 3.
Competing risk analysis for (A) any axillary recurrence (overall cohort); (B) isolated axillary recurrence (overall cohort); (C) any axillary recurrence (stratified by surgical group); (D) isolated axillary recurrence (stratified by surgical group); (E) any invasive recurrence (overall cohort); and (F) any invasive recurrence (stratified by surgical group). ALND, axillary lymph node dissection.
See this image and copyright information in PMC

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