Breast CancerICARONCT06464341
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
An observational study of Breast Cancer, run by University Hospital, Basel, Switzerland at 62 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years, women only
- Conditions the study is for
- Breast Cancer
- Type of treatment
- Injection or infusion
- How many people
- 583 participants
- Where
- 62 sitesin 18 countries
- Study dates
- 4 May 2023to 31 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients will be included. There is no formal sample size calculation
Who may be able to join
- 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
Who cannot join
- Male patients
- Patients with nodal pCR
- Patients with residual nodal micro- or macrometastases
- Stage IV disease at presentation
- Inflammatory breast cancer (T4d) at presentation
Trial locations and contacts
62 sites in 18 countries.
62 sites in 18 countries
United States20 sites
University of Michigan
Ann Arbor, Michigan, 48109
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Duke University
Durham, North Carolina, 27710
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
University of Southern California
Los Angeles, California, 90033
Cedars-Sinai Medical Center, Samuel Oschin Cancer Institute
Los Angeles, California, 90048
Miami University
Miami, Florida, 33136
NYU Langone Health
New York, New York, 10016
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Weill Cornell Medical Center
New York, New York, 10065
Montefiore Medical Center
New York, New York, 10461
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Valleywise Health Medical Center
Phoenix, Arizona, 85008
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
Mayo Clinic
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Guthrie Clinic
Sayre, Pennsylvania, 18840
Swedish Cancer Institute
Seattle, Washington, 98029
University of Washington
Seattle, Washington, 98133
Germany6 sites
Universitätsklinikum Augsburg
Augsburg
University Hospital Düsseldorf
Düsseldorf
KEM Evang. Kliniken Essen-Mitte
Essen
University Hospital Heidelberg
Heidelberg
University Hospital Schleswig-Holstein Campus Lübeck
Lübeck
German Breast Group
Neu-Isenburg
Turkey (Türkiye)6 sites
Gülhane Research and Training Hospital
Ankara
Acıbadem Research Instıtute of Senology
Istanbul
Istanbul University Institute of Oncology
Istanbul
Istanbul University, Faculty of Medicine
Istanbul
Marmara University, School of Medicine
Istanbul
Zonguldak Bulent Ecevit University
Zonguldak
Brazil5 sites
Sirio-Libanes Hospital, Department of Oncology
Brasília
Nossa Senhora das Gracias Hospital
Curitiba
Instituto de Mastologia e Oncologia
Goiânia
Santa Paula Hospital
São Paulo
Sirio-Libanes Hospital, Department of Oncology
São Paulo
Italy5 sites
Instituto Nazionale Tumori (IRCCS)
Naples
University of Naples Federico
Naples
Veneto Institute of Oncology IRCCS
Padua
Istituti Clinici Scientifici Maugeri IRCCS,
Pavia
IRCCS Humanitas Research Hospital
Rozzano
Switzerland4 sites
Kantonsspital Baden
Baden
University Hospital Basel
Basel, Canton of Basel-City, 4031
Breastcenter Zürich
Zurich
University Hospital Zürich
Zurich
South Korea3 sites
Asan Medical Center
Seoul
Gangnam Severance Hospital
Seoul
Samsung Medical Center
Seoul
Greece2 sites
Athens Medical Center
Athens
Heraklion University Hospital
Heraklion
United Kingdom2 sites
Cambridge University Hospital
Cambridge
The Royal Marsden Hospital
London
About this study
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.
Read the 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
- Being tested
- Observational study no intervention
- Keywords
- Axillary lymph node dissection, Isolated tumor cells, Neoadjuvant chemotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational study no interventionOther
Observational study no intervention
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Observational study no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Axillary Lymph Node Dissection (ALND)
Evaluation of the number of ALNDs performed
Measured: Day 0
Number of Tailored Axillary Dissection (TAD)
Evaluation of the number of TAD performed
Measured: Day 0
Number of Sentinel Lymph Node Biopsy (SLNB)
Evaluation of the number of SLNB performed
Measured: one time assessment before surgery
Number Axillary Radiotherapy
Evaluation of the number of axillary radiotherapy performed
Measured: Up to 2 years
Number of additional micrometastases
Evaluation of the number of additional micrometastases removed by ALND
Measured: Day 0
Number of additional macrometastases
Evaluation of the number of additional macrometastases removed by ALND
Measured: Day 0
Axillary recurrence
Evaluation of the number of axillary recurrence
Measured: Up to 14 years
Secondary outcomes (3)
Regional recurrence
Evaluation of the number of regional recurrence
Measured: Up to 14 years
Locoregional recurrence
Evaluation of the number of locoregional recurrence
Measured: Up to 14 years
Invasive recurrence
Evaluation of the number of invasive recurrence
Measured: Up to 14 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start4 May 2023
- Primary completion31 Dec 2023
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 583 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
- Investigators
- Walter P. Weber, MD, Principal investigator, University Hospital, Basel, Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06464341
- Sponsor's protocol ID
- 2023-00418: bb23Weber
- Other IDs
- 2023
- Acronym
- ICARO
- Status last verified
- Jan 2025
- First submitted
- 12 Jun 2024
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 39509672
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06464341
- Acronym / sponsor ID
- ICARO / 2023-00418: bb23Weber
- Conditions
- Breast Cancer
- Keywords
- Axillary lymph node dissection, Isolated tumor cells, Neoadjuvant chemotherapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 583 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Memorial Sloan Kettering Cancer Center
- Study start
- 4 May 2023 (actual)
- Primary completion
- 31 Dec 2023 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 18 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with clinical T1-4 N0-3 breast cancer at diagnosis treated with NAC | – | Other: Observational study no interventionThis 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients will be included. There is no formal sample size calculation
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (5 listed)
- Male patients
- Patients with nodal pCR
- Patients with residual nodal micro- or macrometastases
- Stage IV disease at presentation
- Inflammatory breast cancer (T4d) at presentation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational study no interventionObservational study no intervention | Other | Patients with clinical T1-4 N0-3 breast cancer at diagnosis treated with NAC |
Primary outcome
Number of Axillary Lymph Node Dissection (ALND)
Time frame: Day 0
Evaluation of the number of ALNDs performed
Number of Tailored Axillary Dissection (TAD)
Time frame: Day 0
Evaluation of the number of TAD performed
Number of Sentinel Lymph Node Biopsy (SLNB)
Time frame: one time assessment before surgery
Evaluation of the number of SLNB performed
Number Axillary Radiotherapy
Time frame: Up to 2 years
Evaluation of the number of axillary radiotherapy performed
Number of additional micrometastases
Time frame: Day 0
Evaluation of the number of additional micrometastases removed by ALND
Number of additional macrometastases
Time frame: Day 0
Evaluation of the number of additional macrometastases removed by ALND
Axillary recurrence
Time frame: Up to 14 years
Evaluation of the number of axillary recurrence
3 secondary outcomes
Regional recurrence
Time frame: Up to 14 years
Locoregional recurrence
Time frame: Up to 14 years
Invasive recurrence
Time frame: Up to 14 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- Derived from this study: PubMed 39509672Montagna 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Walter P. Weber, MD principal investigator
University Hospital, Basel, Switzerland
62 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by University Hospital, Basel, Switzerland at 62 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, Germany, Turkey (Türkiye), Brazil, Italy and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Axillary Lymph Node Dissection (ALND) (time frame: Day 0). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06464341, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2025.