Breast CancerAXSANANCT04373655
AXillary Surgery After NeoAdjuvant Treatment
An observational study of Breast Cancer, run by European Breast Cancer Research Association of Surgical Trialists at 1 site in Germany.
Trial summary
The optimal surgical axillary staging technique in patients who convert from the clinically positive to clinically negative lymph node status under neoadjuvant therapy (cN+ → ycN0) remains to be clarified. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- How many people
- 3,000 participants
- Where
- 1 siteGermany
- Study dates
- 28 Apr 2020to Apr 2030
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Breast cancer patients with lymph node metastasis undergoing neoadjuvat chemotherapy.
Who may be able to join
- Signed informed consent form
- Primary invasive breast cancer (confirmed by core biopsy)
- cN+
- cT1-4c
- Scheduled for neoadjuvant systemic therapy
- Female / male patients ≥ 18 years old
Who cannot join
- Distant metastasis
- Recurrent breast cancer
- Inflammatory breast cancer
- Extramammary breast cancer
- Supraclavicular lymph node metastasis
- Pregnancy
- Less than 4 cycles of NACT administered
- Patients not suitable for surgical treatment
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Maggie Banys-Paluchowski, PD Dr. contact
Germany1 site, 1 recruiting
- Recruiting
Klinikum Esslingen
Esslingen am Neckar
Thorsten Kühn, Prof.
About this study
Official title: A Prospective Multicenter Cohort Study to Evaluate Different Surgical Methods of Axillary Staging (Sentinel Lymph Node Biopsy, Targeted Axillary Dissection, Axillary Dissection) in Clinically Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy
The optimal surgical axillary staging technique in patients who convert from the clinically positive to clinically negative lymph node status under neoadjuvant therapy (cN+ → ycN0) remains to be clarified. Different strategies (axillary lymph node dissection, sentinel node biopsy, targeted axillary dissection) are currently used in different countries. A prospective analysis comparing these techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible. Therefore, the EUBREAST study group decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after neoadjuvant therapy.
Read the detailed description
For many decades, axillary lymph node dissection (ALND) has been considered standard of care in breast cancer (BC) patients. The procedure aimed at assessing the pN status to guide adjuvant therapy decisions as well as ensuring adequate locoregional control. However, ALND is associated with high morbidity and may therefore lead to reduced quality of life in BC patients.
In women undergoing primary surgery, ALND as a staging tool has been replaced by the less invasive sentinel lymph node biopsy (SLNB) without compromising the disease-free or overall survival (DFS, OS). Since then, the therapeutic benefit of ALND in patients with clinically occult metastasis in the sentinel lymph node (SLN) has been challenged as well. According to the current national and international guidelines (e.g. ESMO, NCCN, German S3 guideline and AGO recommendations) completion ALND can be safely omitted in selected patients with 1-2 positive sentinel lymph nodes.
The feasibility and safety of the SLNB after neoadjuvant chemotherapy (NACT) has been controversially discussed, particularly regarding women who initially presented with positive lymph nodes (cN+) and converted to ycN0 following NACT. In these patients, two large prospective multicenter trials reported a false-negative rate (FNR) of 12 and 14%, respectively, thus exceeding the generally accepted (albeit arbitrarily chosen) cutoff of 10%. The clinical relevance of an FNR > 10% and its impact on oncological endpoints (DFS, OS) remains unclear. For this reason, numerous national guidelines still recommend ALND in these patients.
Possible ways to further reduce the FNR in cN+ patients have been extensively discussed in the recent years. In 2016, a novel surgical approach (TAD = targeted axillary dissection) has been reported that consists of inserting a marking (e.g. a clip or a radioactive tracer) into the metastatic lymph node before NACT. In patients in whom the marked lymph node (target lymph node = TLN) and the sentinel node had been successfully removed, the FNR was as low as 1.4%. These retrospectively analyzed data from a prospective register support the hypothesis that TAD can improve the relatively low success rates of SLNB and reduce the long-term morbidity of patients undergoing axillary surgery in the neoadjuvant setting.
Several issues regarding currently used axillary staging techniques remain yet to be clarified. Based on the unclear evidence, the guideline recommendations for the cN+ → ycN0 patients differ strongly. The current ESMO guidelines state that (1) SLNB may be carried out in selected cases, and, if negative, further axillary surgery may be avoided and (2) the FNR of SLNB alone can be improved by marking the biopsied positive node(s) to verify the removal. In Germany, the S3 guideline (last version: 2020) recommends ALND in patients with initial nodal involvement. In contrast, the German Working Group Gynecological Oncology (AGO) changed their recommendations in 2019 and endorsed TAD as a technique of choice for this patient subgroup. In several European countries (Sweden, Norway, Finland) ALND is still considered standard of care for these patients. In others, such as Italy, most patients receive SLNB alone without marking and removing the target lymph node. In the current NCCN guidelines the TAD is considered an optional technique. A prospective analysis comparing different techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible and therefore would not clarify currently open issues within a reasonable timeframe.
Based on the lack of sufficient evidence and discrepancies between different national and institutional standards, the EUBREAST study group (www.eubreast.com) decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after NACT.
- Conditions
- Breast Cancer
- Keywords
- breast cancer, neoadjuvant chemotherapy, axillary lymph node dissection, targeted axillary dissection, target lymph node, sentinel node biopsy
- Medical subject headings
- Breast Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
Invasive disease-free survival (iDFS)
iDFS is defined as time from surgery to the first clinical, radiological or histological diagnosis of invasive relapse
Measured: 5 years
Axillary recurrence rate
Axillary recurrence is defined as radiological and/or histological diagnosis of tumor recurrence in the axilla
Measured: 3 years
Health-related quality of life
Health-related QoL will be assessed with the EORTC Quality of life questionnaires
Measured: 5 years
Arm morbidity
Arm morbidity will be assessed with the Lymph IFC questionnaire
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2020
- Study start28 Apr 2020
- Primary completionApr 2030 (estimated)
- Study completionApr 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- 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
- Prospective
- Enrolment
- 3,000 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- European Breast Cancer Research Association of Surgical Trialists
- Sponsor type
- Research network
- Collaborators
- AWOgyn, AGO-B, North Eastern German Society of Gynaecological Oncology, GBG Forschungs GmbH, Claudia von Schilling Foundation for Breast Cancer Research, Ehmann-Stiftung Savognin
- Responsible party
- Sponsor
- Investigators
- Thorsten Kühn, Prof., Study chair, European Breast Cancer Research Association of Surgical Trialists
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04373655
- Sponsor's protocol ID
- EUBREAST 3
- Acronym
- AXSANA
- Status last verified
- Sep 2026
- First submitted
- 29 Apr 2020
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Banys-Paluchowski M, Hartmann S, de Boniface J, Gentilini OD, Ditsch N, Stickeler E, Karadeniz Cakmak G, Hauptmann M, Schroth J, Thill M, di Micco R, Hahn M, Murawa D, Rubio IT, Pinto D, Kontos M, Niinikoski L, Gasparri ML, Nina H, Rebaza LP, Frohlich S, Schmidt E, Wihlfahrt K, Berger T, Basali T, Ruf F, Rief A, Bonci EA, Peintinger F, Schlichting E, Valiyeva Qanimat H, Vanhoeij M, Kadayaprath G, Dostalek L, Kothari A, Perhavec A, Ivanov T, Zippel D, Adamczyk B, Porpiglia M, Gurleyik GM, Untch M, Lux MP, Jursik K, Kolberg HC, Reimer T, Tauber N, Rody A, Matrai Z, Krawczyk N, Thongvitokomarn S, Kuhn T. Marking Techniques for Target Lymph Nodes in Node-Positive Breast Cancer Treated With Neoadjuvant Therapy in the AXSANA/EUBREAST-03/AGO-B-053 Study. J Clin Oncol. 2026 Mar;44(7):575-585. doi: 10.1200/JCO-25-01921. Epub 2026 Jan 21.
PubMed 41564379Banys-Paluchowski M, Hartmann S, Basali T, Gasparri ML, de Boniface J, Gentilini OD, Cakmak GK, Ditsch N, Stickeler E, Schlichting E, Rubio I, Peintinger F, Untch M, Mau C, Federspiel FK, Bucher S, Ramaker K, Paluchowski P, Bauer L, Riemer S, Langanke D, Leuf TD, Schnabel J, von Abel E, Solbach C, Ovalle SC, Hilmer K, Bjelic-Radisic V, Stahl N, Sanchez-Mendez JI, Hagen V, Hansen MH, Krawczyk N, Sezen BA, Jursik K, Thill M, Kolberg HC, Reimer T, Ruf F, Wihlfahrt K, Rief A, Berger T, Schmidt E, Tauber N, Frohlich S, Kuhn T. Radar reflectors for marking of target lymph nodes in initially node-positive patients receiving neoadjuvant chemotherapy for breast cancer-a subgroup analysis of the prospective AXSANA (EUBREAST-03) trial. Breast Cancer Res Treat. 2025 May;211(1):203-211. doi: 10.1007/s10549-025-07635-4. Epub 2025 Feb 20.
PubMed 39976867Hartmann S, Banys-Paluchowski M, Stickeler E, de Boniface J, Gentilini OD, Kontos M, Seitz S, Kaltenecker G, Warnberg F, Zetterlund LH, Kolberg HC, Frohlich S, Kuhn T. Applicability of magnetic seeds for target lymph node biopsy after neoadjuvant chemotherapy in initially node-positive breast cancer patients: data from the AXSANA study. Breast Cancer Res Treat. 2023 Dec;202(3):497-504. doi: 10.1007/s10549-023-07100-0. Epub 2023 Sep 8.
PubMed 37684426
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multicenter Cohort Study to Evaluate Different Surgical Methods of Axillary Staging (Sentinel Lymph Node Biopsy, Targeted Axillary Dissection, Axillary Dissection) in Clinically Node-positive Breast Cancer Patients Treated With Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT04373655
- Acronym / sponsor ID
- AXSANA / EUBREAST 3
- Conditions
- Breast Cancer
- Keywords
- breast cancer, neoadjuvant chemotherapy, axillary lymph node dissection, targeted axillary dissection, target lymph node, sentinel node biopsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- European Breast Cancer Research Association of Surgical TrialistsResearch network
- Collaborators
- AWOgyn, AGO-B, North Eastern German Society of Gynaecological Oncology, GBG Forschungs GmbH, Claudia von Schilling Foundation for Breast Cancer Research, Ehmann-Stiftung Savognin
- Study start
- 28 Apr 2020 (actual)
- Primary completion
- Apr 2030 (estimated)
- Study completion
- Apr 2030 (estimated)
- First posted
- 4 May 2020 (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 optimal surgical axillary staging technique in patients who convert from the clinically positive to clinically negative lymph node status under neoadjuvant therapy (cN+ → ycN0) remains to be clarified. Different strategies (axillary lymph node dissection, sentinel node biopsy, targeted axillary dissection) are currently used in different countries. A prospective analysis comparing these techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible. Therefore, the EUBREAST study group decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after neoadjuvant therapy.
Detailed description
For many decades, axillary lymph node dissection (ALND) has been considered standard of care in breast cancer (BC) patients. The procedure aimed at assessing the pN status to guide adjuvant therapy decisions as well as ensuring adequate locoregional control. However, ALND is associated with high morbidity and may therefore lead to reduced quality of life in BC patients.
In women undergoing primary surgery, ALND as a staging tool has been replaced by the less invasive sentinel lymph node biopsy (SLNB) without compromising the disease-free or overall survival (DFS, OS). Since then, the therapeutic benefit of ALND in patients with clinically occult metastasis in the sentinel lymph node (SLN) has been challenged as well. According to the current national and international guidelines (e.g. ESMO, NCCN, German S3 guideline and AGO recommendations) completion ALND can be safely omitted in selected patients with 1-2 positive sentinel lymph nodes.
The feasibility and safety of the SLNB after neoadjuvant chemotherapy (NACT) has been controversially discussed, particularly regarding women who initially presented with positive lymph nodes (cN+) and converted to ycN0 following NACT. In these patients, two large prospective multicenter trials reported a false-negative rate (FNR) of 12 and 14%, respectively, thus exceeding the generally accepted (albeit arbitrarily chosen) cutoff of 10%. The clinical relevance of an FNR > 10% and its impact on oncological endpoints (DFS, OS) remains unclear. For this reason, numerous national guidelines still recommend ALND in these patients.
Possible ways to further reduce the FNR in cN+ patients have been extensively discussed in the recent years. In 2016, a novel surgical approach (TAD = targeted axillary dissection) has been reported that consists of inserting a marking (e.g. a clip or a radioactive tracer) into the metastatic lymph node before NACT. In patients in whom the marked lymph node (target lymph node = TLN) and the sentinel node had been successfully removed, the FNR was as low as 1.4%. These retrospectively analyzed data from a prospective register support the hypothesis that TAD can improve the relatively low success rates of SLNB and reduce the long-term morbidity of patients undergoing axillary surgery in the neoadjuvant setting.
Several issues regarding currently used axillary staging techniques remain yet to be clarified. Based on the unclear evidence, the guideline recommendations for the cN+ → ycN0 patients differ strongly. The current ESMO guidelines state that (1) SLNB may be carried out in selected cases, and, if negative, further axillary surgery may be avoided and (2) the FNR of SLNB alone can be improved by marking the biopsied positive node(s) to verify the removal. In Germany, the S3 guideline (last version: 2020) recommends ALND in patients with initial nodal involvement. In contrast, the German Working Group Gynecological Oncology (AGO) changed their recommendations in 2019 and endorsed TAD as a technique of choice for this patient subgroup. In several European countries (Sweden, Norway, Finland) ALND is still considered standard of care for these patients. In others, such as Italy, most patients receive SLNB alone without marking and removing the target lymph node. In the current NCCN guidelines the TAD is considered an optional technique. A prospective analysis comparing different techniques regarding feasibility, safety, morbidity and surgical effort is urgently needed. Due to high complexity and discordant recommendations, a randomized trial comparing different techniques is hardly feasible and therefore would not clarify currently open issues within a reasonable timeframe.
Based on the lack of sufficient evidence and discrepancies between different national and institutional standards, the EUBREAST study group (www.eubreast.com) decided to initiate a prospective cohort study as an international project that aims at comparatively evaluating data on axillary staging after NACT.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 5 Years
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Breast cancer patients with lymph node metastasis undergoing neoadjuvat chemotherapy.
Key inclusion criteria (6 listed)
- Signed informed consent form
- Primary invasive breast cancer (confirmed by core biopsy)
- cN+
- cT1-4c
- Scheduled for neoadjuvant systemic therapy
Key exclusion criteria (8 listed)
- Distant metastasis
- Recurrent breast cancer
- Inflammatory breast cancer
- Extramammary breast cancer
- Supraclavicular lymph node metastasis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Invasive disease-free survival (iDFS)
Time frame: 5 years
iDFS is defined as time from surgery to the first clinical, radiological or histological diagnosis of invasive relapse
Axillary recurrence rate
Time frame: 3 years
Axillary recurrence is defined as radiological and/or histological diagnosis of tumor recurrence in the axilla
Health-related quality of life
Time frame: 5 years
Health-related QoL will be assessed with the EORTC Quality of life questionnaires
Arm morbidity
Time frame: 5 years
Arm morbidity will be assessed with the Lymph IFC questionnaire
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Derived from this study: PubMed 41564379Banys-Paluchowski M, Hartmann S, de Boniface J, Gentilini OD, Ditsch N, Stickeler E, Karadeniz Cakmak G, Hauptmann M, Schroth J, Thill M, di Micco R, Hahn M, Murawa D, Rubio IT, Pinto D, Kontos M, Niinikoski L, Gasparri ML, Nina H, Rebaza LP, Frohlich S, Schmidt E, Wihlfahrt K, Berger T, Basali T, Ruf F, Rief A, Bonci EA, Peintinger F, Schlichting E, Valiyeva Qanimat H, Vanhoeij M, Kadayaprath G, Dostalek L, Kothari A, Perhavec A, Ivanov T, Zippel D, Adamczyk B, Porpiglia M, Gurleyik GM, Untch M, Lux MP, Jursik K, Kolberg HC, Reimer T, Tauber N, Rody A, Matrai Z, Krawczyk N, Thongvitokomarn S, Kuhn T. Marking Techniques for Target Lymph Nodes in Node-Positive Breast Cancer Treated With Neoadjuvant Therapy in the AXSANA/EUBREAST-03/AGO-B-053 Study. J Clin Oncol. 2026 Mar;44(7):575-585. doi: 10.1200/JCO-25-01921. Epub 2026 Jan 21.
- Derived from this study: PubMed 39976867Banys-Paluchowski M, Hartmann S, Basali T, Gasparri ML, de Boniface J, Gentilini OD, Cakmak GK, Ditsch N, Stickeler E, Schlichting E, Rubio I, Peintinger F, Untch M, Mau C, Federspiel FK, Bucher S, Ramaker K, Paluchowski P, Bauer L, Riemer S, Langanke D, Leuf TD, Schnabel J, von Abel E, Solbach C, Ovalle SC, Hilmer K, Bjelic-Radisic V, Stahl N, Sanchez-Mendez JI, Hagen V, Hansen MH, Krawczyk N, Sezen BA, Jursik K, Thill M, Kolberg HC, Reimer T, Ruf F, Wihlfahrt K, Rief A, Berger T, Schmidt E, Tauber N, Frohlich S, Kuhn T. Radar reflectors for marking of target lymph nodes in initially node-positive patients receiving neoadjuvant chemotherapy for breast cancer-a subgroup analysis of the prospective AXSANA (EUBREAST-03) trial. Breast Cancer Res Treat. 2025 May;211(1):203-211. doi: 10.1007/s10549-025-07635-4. Epub 2025 Feb 20.
- Derived from this study: PubMed 37684426Hartmann S, Banys-Paluchowski M, Stickeler E, de Boniface J, Gentilini OD, Kontos M, Seitz S, Kaltenecker G, Warnberg F, Zetterlund LH, Kolberg HC, Frohlich S, Kuhn T. Applicability of magnetic seeds for target lymph node biopsy after neoadjuvant chemotherapy in initially node-positive breast cancer patients: data from the AXSANA study. Breast Cancer Res Treat. 2023 Dec;202(3):497-504. doi: 10.1007/s10549-023-07100-0. Epub 2023 Sep 8.
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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.
Maggie Banys-Paluchowski, PD Dr. contact
Thorsten Kühn, Prof. study chair
European Breast Cancer Research Association of Surgical Trialists
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer, run by European Breast Cancer Research Association of Surgical Trialists at 1 site in Germany.
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 6 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thorsten Kühn, Prof. (+49711 3103-3051 ext. +4971131033051, info@eubreast.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Invasive disease-free survival (iDFS) (time frame: 5 years). The study lists 4 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 NCT04373655, which also lists 3 linked publications.
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 15 Sep 2026.