Breast CancerPRO-TuFEst-LNNCT07304934
A Prospective Multicenter Study of the TuFEst-LN Model for Axillary Lymph Node Status Assessment in Breast Cancer
An observational study of Breast Cancer and Axillary Lymph Node Metastasis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
Through the research of this project, we expect to validate the clinical utility of the TuFEst-LN model in assessing axillary lymph node status in breast cancer patients. Specifically, we aim to prospectively validate its ability to identify pathologically node-negative patients among clinically and radiologically… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Axillary Lymph Node Metastasis
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 1 Aug 2025to 31 Dec 2027
- How long will I take part?
- 1 Year
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Breast cancer patients receiving care across the six participating centers who fulfill the eligibility criteria for either the cN0 cohort undergoing upfront surgery or the initially cN+ cohort after neoadjuvant systemic therapy.
Who may be able to join
None listed.
Who cannot join
- Participants meeting any of the following criteria will be excluded:
- Pregnancy or breastfeeding.
- Prior surgical removal of the primary breast lesion before enrollment, resulting in inability to obtain the required preoperative blood samples.
- Presence of confirmed distant metastasis.
- Presence of supraclavicular, internal mammary, or other lymph node lesions that cannot be adequately assessed by planned surgery and pathological evaluation.
- History of another active malignancy within the previous 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, or other malignancies considered by investigators unlikely to affect study outcomes.
Show all 10Show fewer
- Receipt of whole blood, plasma, or other blood product transfusion within 30 days prior to enrollment.
- Insufficient plasma sample volume, severe hemolysis, or failure to meet cfDNA sequencing quality control requirements determined by the central laboratory.
- Absence of evaluable axillary surgical pathological results.
- Any other condition considered by the investigator to make the patient unsuitable for participation in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Second affiliated hospital of Medical school, Zhejiang university
Hangzhou, Zhejiang
Yao Dr, +8613989463951, drnichao@zju.edu.cn
About this study
Official title: A Prospective Multi-center Cohort Study Based on Deep Learning-based cfDNA Fragment Omics to Verify the TuFEst Model for Axillary Lymph Node Status Assessment in Breast Cancer Patients Undergoing Primary Surgery or Neoadjuvant Therapy
Through the research of this project, we expect to validate the clinical utility of the TuFEst-LN model in assessing axillary lymph node status in breast cancer patients. Specifically, we aim to prospectively validate its ability to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients undergoing upfront surgery ，and explore the predictive value of the TuFEst-LN model combined with preoperative MRI for ypN status assessment in initially node-positive patients following neoadjuvant therapy.
Read the detailed description
Through the research of this project, we aim to prospectively validate the locked TuFEst-LN model, a cfDNA fragmentomics-based liquid biopsy model, for axillary lymph node status assessment in patients with breast cancer. This study will evaluate the ability of the TuFEst-LN model to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients with cT1-3 invasive breast cancer undergoing upfront surgery without neoadjuvant therapy. In addition, this study will explore the predictive value of the TuFEst-LN model combined with preoperative magnetic resonance imaging (MRI) for post-neoadjuvant pathological axillary lymph node status (ypN) in initially node-positive breast cancer patients. Peripheral blood samples and clinical data will be prospectively collected from multiple centers, and model predictions will be compared with final surgical pathology as the reference standard. This study aims to validate the clinical utility of cfDNA fragmentomics-based liquid biopsy for noninvasive axillary lymph node assessment and provide evidence for individualized axillary management in breast cancer.
- Conditions
- Breast Cancer, Axillary Lymph Node Metastasis
- Being tested
- No Intervention: Observational Cohort
- Keywords
- breast cancer, cfDNA, TuFEst model, Fragmentomics, Axillary lymph node, Sentinel lymph node biopsy, Neoadjuvant therapy, Magnetic resonance imaging, Diagnostic accuracy, Machine learning
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No Intervention: Observational CohortOther
No Intervention: Observational Cohort
| Study group | Role | What they receive |
|---|---|---|
| 1 | Invasive breast cancer patients with cT1-3N0M0 disease who have received no prior neoadjuvant therapy or radiotherapy and undergo SLNB and/or ALND for axillary evaluation. A total of 300 participants are planned to be enrolled in Cohort 1 Receives: Other: No Intervention: Observational Cohort | |
| 2 | Patients with newly diagnosed invasive breast cancer and biopsy-confirmed axillary lymph node metastasis without distant metastasis, who are scheduled to receive standard neoadjuvant systemic therapy followed by breast and axillary surgery . Patients who complete or prematurely discontinue neoadjuvant therapy for clinical reasons but proceed to surgery are eligible.At least 100 participants are planned to be enrolled in Cohort 2. Receives: Other: No Intervention: Observational Cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological axillary lymph node positivity rate among TuFEst-LN-negative patients
Defined as the proportion of patients with pathological axillary lymph node positivity (pN1mi or higher) among patients predicted as negative by the locked TuFEst-LN model in Cohort 1. FOR = FN/(TN+FN) = 1-NPV.
Measured: up to 2 weeks
Secondary outcomes (7)
Negative Predictive Value (NPV) of the TuFEst-LN Model
The proportion of patients with negative pathological axillary lymph node status (pN0 or pN0(i+)) among patients classified as negative by the locked TuFEst-LN model.
Measured: 2 weeks
Sensitivity and False Negative Rate (FNR) for Detecting Pathological Axillary Lymph Node Positivity
The ability of the locked TuFEst-LN model to identify patients with pathological axillary lymph node metastasis (pN1mi or higher). FNR is defined as 1-sensitivity.
Measured: 2 weeks
Specificity of the TuFEst-LN Model
The proportion of patients with true pathological node-negative status (pN0 or pN0(i+)) who are correctly classified as negative by the locked TuFEst-LN model.
Measured: 2 weeks
Positive Predictive Value (PPV), Overall Accuracy, and Discrimination Performance
Evaluation of the predictive performance of the locked TuFEst-LN model, including PPV, overall accuracy, area under the receiver operating characteristic curve (ROC-AUC), area under the precision-recall curve (PR-AUC), and likelihood ratios.
Measured: 2 weeks
Proportion of Patients Classified as Negative by the TuFEst-LN Model
The proportion of evaluable patients in Cohort 1 who are classified as negative by the locked TuFEst-LN model, used to estimate the potential rate of sentinel lymph node biopsy (SLNB) omission.
Measured: 2 weeks
Calibration and Net Clinical Benefit of the TuFEst-LN Model
Assessment of model calibration and clinical utility using Brier score, calibration intercept, calibration slope, calibration curve, and decision curve analysis.
Measured: 2 weeks
Pathological Burden of Missed Positive Cases
Evaluation of pathological characteristics among false-negative patients, including the number of micrometastatic and macrometastatic lymph node cases, extranodal extension, and other adverse pathological features.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2025
- Study start1 Aug 2025
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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
- Prospective
- Enrolment
- 400 participants (estimated)
- Target duration
- 1 Year
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Shandong Cancer Hospital and Institute, Suzhou Municipal Hospital, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, First People's Hospital of Hangzhou, Ningbo Medical Center Lihuili Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07304934
- Sponsor's protocol ID
- 2025-1028
- Acronym
- PRO-TuFEst-LN
- Status last verified
- Oct 2025
- First submitted
- 19 Nov 2025
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bruhm DC, Vulpescu NA, Foda ZH, Phallen J, Scharpf RB, Velculescu VE. Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection. Nat Rev Cancer. 2025 May;25(5):341-358. doi: 10.1038/s41568-025-00795-x. Epub 2025 Mar 4.
PubMed 40038442Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, Luini A, Viale G, Cassano E, Peradze N, Toesca A, Massari G, Sacchini V, Munzone E, Leonardi MC, Cattadori F, Di Micco R, Esposito E, Sgarella A, Cattaneo S, Busani M, Dessena M, Bianchi A, Cretella E, Ripoll Orts F, Mueller M, Tinterri C, Chahuan Manzur BJ, Benedetto C, Veronesi P; SOUND Trial Group. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial. JAMA Oncol. 2023 Nov 1;9(11):1557-1564. doi: 10.1001/jamaoncol.2023.3759.
PubMed 37733364Reimer T, Stachs A, Veselinovic K, Kuhn T, Heil J, Polata S, Marme F, Muller T, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Zahm DM, Thill M, Golatta M, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025 Mar 13;392(11):1051-1064. doi: 10.1056/NEJMoa2412063. Epub 2024 Dec 12.
PubMed 39665649Zhu Y, Zheng S, Shao Y, Zhou J, Gu X, Shen L, Li X, Liu W, Xue W, Lu H, Zhou J, Ding J, Deng H, Chen J, Yu Z, Yao Y, Xia W, Chen W, Sun S, Wang Z, Qian T, Yu X, Liu J, Chen Y, Lin Z, Huang J, Ni C. Fragmentomic liquid biopsy enables early breast cancer detection, molecular subtyping and lymph node assessment. Nat Commun. 2026 Mar 6;17(1):2276. doi: 10.1038/s41467-026-70204-w.
PubMed 41792156
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Multi-center Cohort Study Based on Deep Learning-based cfDNA Fragment Omics to Verify the TuFEst Model for Axillary Lymph Node Status Assessment in Breast Cancer Patients Undergoing Primary Surgery or Neoadjuvant Therapy
- ClinicalTrials.gov ID
- NCT07304934
- Acronym / sponsor ID
- PRO-TuFEst-LN / 2025-1028
- Conditions
- Breast Cancer, Axillary Lymph Node Metastasis
- Keywords
- breast cancer, cfDNA, TuFEst model, Fragmentomics, Axillary lymph node, Sentinel lymph node biopsy, Neoadjuvant therapy, Magnetic resonance imaging
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Collaborators
- Shandong Cancer Hospital and Institute, Suzhou Municipal Hospital, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, First People's Hospital of Hangzhou, Ningbo Medical Center Lihuili Hospital
- Study start
- 1 Aug 2025 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 26 Dec 2025 (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.
Through the research of this project, we expect to validate the clinical utility of the TuFEst-LN model in assessing axillary lymph node status in breast cancer patients. Specifically, we aim to prospectively validate its ability to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients undergoing upfront surgery ，and explore the predictive value of the TuFEst-LN model combined with preoperative MRI for ypN status assessment in initially node-positive patients following neoadjuvant therapy.
Detailed description
Through the research of this project, we aim to prospectively validate the locked TuFEst-LN model, a cfDNA fragmentomics-based liquid biopsy model, for axillary lymph node status assessment in patients with breast cancer. This study will evaluate the ability of the TuFEst-LN model to identify pathologically node-negative patients among clinically and radiologically assessed cN0 patients with cT1-3 invasive breast cancer undergoing upfront surgery without neoadjuvant therapy. In addition, this study will explore the predictive value of the TuFEst-LN model combined with preoperative magnetic resonance imaging (MRI) for post-neoadjuvant pathological axillary lymph node status (ypN) in initially node-positive breast cancer patients. Peripheral blood samples and clinical data will be prospectively collected from multiple centers, and model predictions will be compared with final surgical pathology as the reference standard. This study aims to validate the clinical utility of cfDNA fragmentomics-based liquid biopsy for noninvasive axillary lymph node assessment and provide evidence for individualized axillary management in breast cancer.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Year
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Other: No Intervention: Observational CohortInvasive breast cancer patients with cT1-3N0M0 disease who have received no prior neoadjuvant therapy or radiotherapy and undergo SLNB and/or ALND for axillary evaluation. A total of 300 participants are planned to be enrolled in Cohort 1 |
| 2 | – | Other: No Intervention: Observational CohortPatients with newly diagnosed invasive breast cancer and biopsy-confirmed axillary lymph node metastasis without distant metastasis, who are scheduled to receive standard neoadjuvant systemic therapy followed by breast and axillary surgery . Patients who complete or prematurely discontinue neoadjuvant therapy for clinical reasons but proceed to surgery are eligible.At least 100 participants are planned to be enrolled in Cohort 2. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Breast cancer patients receiving care across the six participating centers who fulfill the eligibility criteria for either the cN0 cohort undergoing upfront surgery or the initially cN+ cohort after neoadjuvant systemic therapy.
Key inclusion criteria (0 listed)
Key exclusion criteria (10 listed)
- Pregnancy or breastfeeding.
- Prior surgical removal of the primary breast lesion before enrollment, resulting in inability to obtain the required preoperative blood samples.
- Presence of confirmed distant metastasis.
- Presence of supraclavicular, internal mammary, or other lymph node lesions that cannot be adequately assessed by planned surgery and pathological evaluation.
- History of another active malignancy within the previous 5 years, except for cured non-melanoma skin cancer, cervical carcinoma in situ, or other malignancies considered by investigators unlikely to affect study outcomes.
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 |
|---|---|---|
| No Intervention: Observational CohortNo Intervention: Observational Cohort | Other | 1, 2 |
Primary outcome
Pathological axillary lymph node positivity rate among TuFEst-LN-negative patients
Time frame: up to 2 weeks
Defined as the proportion of patients with pathological axillary lymph node positivity (pN1mi or higher) among patients predicted as negative by the locked TuFEst-LN model in Cohort 1. FOR = FN/(TN+FN) = 1-NPV.
7 secondary outcomes
Negative Predictive Value (NPV) of the TuFEst-LN Model
Time frame: 2 weeks
Sensitivity and False Negative Rate (FNR) for Detecting Pathological Axillary Lymph Node Positivity
Time frame: 2 weeks
Specificity of the TuFEst-LN Model
Time frame: 2 weeks
Positive Predictive Value (PPV), Overall Accuracy, and Discrimination Performance
Time frame: 2 weeks
Proportion of Patients Classified as Negative by the TuFEst-LN Model
Time frame: 2 weeks
Calibration and Net Clinical Benefit of the TuFEst-LN Model
Time frame: 2 weeks
Pathological Burden of Missed Positive Cases
Time frame: 2 weeks
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 10 Aug 2026.
- Background: PubMed 40038442Bruhm DC, Vulpescu NA, Foda ZH, Phallen J, Scharpf RB, Velculescu VE. Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection. Nat Rev Cancer. 2025 May;25(5):341-358. doi: 10.1038/s41568-025-00795-x. Epub 2025 Mar 4.
- Background: PubMed 37733364Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, Luini A, Viale G, Cassano E, Peradze N, Toesca A, Massari G, Sacchini V, Munzone E, Leonardi MC, Cattadori F, Di Micco R, Esposito E, Sgarella A, Cattaneo S, Busani M, Dessena M, Bianchi A, Cretella E, Ripoll Orts F, Mueller M, Tinterri C, Chahuan Manzur BJ, Benedetto C, Veronesi P; SOUND Trial Group. Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial. JAMA Oncol. 2023 Nov 1;9(11):1557-1564. doi: 10.1001/jamaoncol.2023.3759.
- Background: PubMed 39665649Reimer T, Stachs A, Veselinovic K, Kuhn T, Heil J, Polata S, Marme F, Muller T, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Zahm DM, Thill M, Golatta M, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025 Mar 13;392(11):1051-1064. doi: 10.1056/NEJMoa2412063. Epub 2024 Dec 12.
- Background: PubMed 41792156Zhu Y, Zheng S, Shao Y, Zhou J, Gu X, Shen L, Li X, Liu W, Xue W, Lu H, Zhou J, Ding J, Deng H, Chen J, Yu Z, Yao Y, Xia W, Chen W, Sun S, Wang Z, Qian T, Yu X, Liu J, Chen Y, Lin Z, Huang J, Ni C. Fragmentomic liquid biopsy enables early breast cancer detection, molecular subtyping and lymph node assessment. Nat Commun. 2026 Mar 6;17(1):2276. doi: 10.1038/s41467-026-70204-w.
- 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.
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 and Axillary Lymph Node Metastasis, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
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 0 inclusion and 10 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 10 Aug 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 China. 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 Chao Ni (+8613989463951, drnichao@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological axillary lymph node positivity rate among TuFEst-LN-negative patients (time frame: up to 2 weeks). 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 NCT07304934, which also lists 4 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 10 Aug 2026.