Nodal Burden and Nodal Recurrence in Patients With Isolated Tumor Cells After Neoadjuvant Chemotherapy Treated With Axillary Dissection or Nodal Radiation: the OPBC-05/EUBREAST-14R/ICARO Study

NCT ID: NCT06464341

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 583 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-05-04
• Study Completion Date: 2024-12-31

Brief Summary

The purposes of this multicenter retrospective cohort study are to determine the residual nodal burden in patients with isolated tumor cells detected in the SLN or the clipped node after NAC and to determine oncologic outcomes in this group of patients after ALND or nodal RT or observation.

Detailed Description

In the context of upfront surgery, the extent of disease in the sentinel lymph nodes (SLNs) significantly predicts the chances of additional non-SLN metastases during axillary lymph node dissection (ALND). For patients with minimal SLN disease (isolated tumor cells [ITCs] and micrometastases), the probability of further non-SLN metastases is between 10-20%. In contrast, for patients with macrometastases, the risk increases to 27-33%.

In patients undergoing neoadjuvant chemotherapy (NAC), those with positive SLNs exhibit a greater residual nodal burden compared to those treated with upfront surgery. For patients with remaining micro- or macrometastases post-NAC, additional positive lymph nodes are found in over 60% of ALND specimens, regardless of receptor subtype. Consequently, ALND remains the standard care for any residual nodal disease after NAC.

Residual ITCs after NAC are present in about 1.5% of all patients undergoing NAC. There is limited data on the likelihood of discovering additional positive lymph nodes in this group, with fewer than 35 documented cases examining residual nodal burden. Therefore, the benefit of ALND for minimal residual disease is uncertain, and axillary management for patients with nodal ITCs is not standardized. Although omitting ALND reduces arm morbidity, identifying residual nodal disease can influence adjuvant therapy recommendations. Despite the lack of consensus on the oncologic safety of omitting ALND in this group, care patterns indicate a growing adoption of this approach. Given the rarity of this clinical scenario and the absence of forthcoming prospective studies, this study utilized real-world data from a large international cohort to determine the incidence of residual non-SLN involvement in patients with ITCs in the SLNs post-NAC, and to compare clinical outcomes in patients with and without ALND as definitive axillary treatment.

Conditions

Breast Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Patients with clinical T1-4 N0-3 breast cancer at diagnosis treated with NAC

This cohort study retrospectively analyzed data from 62 centers in 18 countries, mostly members of the Oncoplastic Breast Consortium (OPBC) network. Patients with clinical T1-4 N0-3 breast cancer at diagnosis treated with neoadjuvant chemotherapy between March 2008 and May 2022 were included if they had isolated tumor cells only. ITCs were defined as clusters of tumor cells ≤0.2 mm or clusters of \<200 cells in a single cross-sectional image, determined by sentinel lymph node biopsy, targeted axillary dissection, or the MARI procedure (marking axillary lymph nodes with radioactive iodine seeds). Excluded: patients with inflammatory breast cancer, stage IV disease at presentation, axillary lymph node dissection as a primary procedure, and neoadjuvant endocrine therapy. Also excluded cases with micrometastases or macrometastases in any sentinel lymph nodes at frozen section or final pathology, and those where ITCs were detected by One Step Nucleic Acid Amplification.

Observational study no intervention

Intervention Type: OTHER

Observational study no intervention

Interventions

Observational study no intervention

Observational study no intervention

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Consecutive patients affected with T1-4 N0-3 breast cancer
• For cN+: Biopsy proven confirmation is required
• For cN0: any axillary staging technique including palpation is allowed
• Residual ITCs in the SLN or clipped node
• At least 1-year follow-up (12/2021 or later depending on the time of data collection)
• For cN0: SLNB with single or dual tracer mapping
• For cN+: SLNB with dual mapping or targeted axillary dissection (TAD: imaging-guided localization of sampled node in combination with SLN procedure with or without dual mapping)
• Underwent TAD/SLNB +/- ALND +/- axillary RT

Exclusion Criteria

• Male patients
• Patients with nodal pCR
• Patients with residual nodal micro- or macrometastases
• Stage IV disease at presentation
• Inflammatory breast cancer (T4d) at presentation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter P. Weber, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Basel, Switzerland

Locations

Valleywise Health Medical Center

Phoenix, Arizona, United States

University of Southern California

Los Angeles, California, United States

Cedars-Sinai Medical Center, Samuel Oschin Cancer Institute

Los Angeles, California, United States

Miami University

Miami, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

NYU Langone Health

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical Center

New York, New York, United States

Montefiore Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Duke University

Durham, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Guthrie Clinic

Sayre, Pennsylvania, United States

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Swedish Cancer Institute

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Medical University of Vienna

Vienna, , Austria

University Hospital Ghent

Ghent, , Belgium

Sirio-Libanes Hospital, Department of Oncology

Brasília, , Brazil

Nossa Senhora das Gracias Hospital

Curitiba, , Brazil

Instituto de Mastologia e Oncologia

Goiânia, , Brazil

Santa Paula Hospital

São Paulo, , Brazil

Sirio-Libanes Hospital, Department of Oncology

São Paulo, , Brazil

Mc Gill University

Montreal, , Canada

Universitätsklinikum Augsburg

Augsburg, , Germany

University Hospital Düsseldorf

Düsseldorf, , Germany

KEM Evang. Kliniken Essen-Mitte

Essen, , Germany

University Hospital Heidelberg

Heidelberg, , Germany

University Hospital Schleswig-Holstein Campus Lübeck

Lübeck, , Germany

German Breast Group

Neu-Isenburg, , Germany

Athens Medical Center

Athens, , Greece

Heraklion University Hospital

Heraklion, , Greece

Sheba Medical Center

Tel Litwinsky, , Israel

Instituto Nazionale Tumori (IRCCS)

Naples, , Italy

University of Naples Federico

Naples, , Italy

Veneto Institute of Oncology IRCCS

Padua, , Italy

Istituti Clinici Scientifici Maugeri IRCCS,

Pavia, , Italy

IRCCS Humanitas Research Hospital

Rozzano, , Italy

Antoni van Leeuwenhoek

Amsterdam, , Netherlands

University Hospital of Zielona Góra

Zielona Góra, , Poland

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Asan Medical Center

Seoul, , South Korea

Gangnam Severance Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Hospital del Mar

Barcelona, , Spain

Sahlgrenska University Hospital Gothenburg

Gothenburg, , Sweden

University Hospital Basel

Basel, Canton of Basel-City, Switzerland

Kantonsspital Baden

Baden, , Switzerland

Breastcenter Zürich

Zurich, , Switzerland

University Hospital Zürich

Zurich, , Switzerland

Gülhane Research and Training Hospital

Ankara, , Turkey (Türkiye)

Acıbadem Research Instıtute of Senology

Istanbul, , Turkey (Türkiye)

Istanbul University Institute of Oncology

Istanbul, , Turkey (Türkiye)

Istanbul University, Faculty of Medicine

Istanbul, , Turkey (Türkiye)

Marmara University, School of Medicine

Istanbul, , Turkey (Türkiye)

Zonguldak Bulent Ecevit University

Zonguldak, , Turkey (Türkiye)

Cambridge University Hospital

Cambridge, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

Countries

United States; Austria; Belgium; Brazil; Canada; Germany; Greece; Israel; Italy; Netherlands; Poland; Slovenia; South Korea; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

Montagna G, Laws A, Ferrucci M, Mrdutt MM, Sun SX, Bademler S, Balbaloglu H, Balint-Lahat N, Banys-Paluchowski M, Barrio AV, Benson J, Bese N, Boughey JC, Boyle MK, Diego EJ, Eden C, Eller R, Goldschmidt M, Hlavin C, Heidinger M, Jelinska J, Karadeniz Cakmak G, Kesmodel SB, King TA, Kuerer HM, Loesch J, Milardi F, Murawa D, Moo TA, Menes TS, Passeri D, Pastoriza JM, Perhavec A, Pislar N, Polidorio N, Rami A, Ryu JM, Schulz A, Sevilimedu V, Ugurlu MU, Uras C, van Hemert A, Wong SM, Yoo TR, Zhang JQ, Karanlik H, Cabioglu N, Peeters MV, Morrow M, Weber WP; ICARO Study Group. Nodal Burden and Oncologic Outcomes in Patients With Residual Isolated Tumor Cells After Neoadjuvant Chemotherapy (ypN0i+): The OPBC-05/ICARO Study. J Clin Oncol. 2025 Mar;43(7):810-820. doi: 10.1200/JCO.24.01052. Epub 2024 Nov 7.

Reference Type: DERIVED

PMID: 39509672 (View on PubMed)

Other Identifiers

2023-00418: bb23Weber

Identifier Type: -

Identifier Source: org_study_id