A Study on Predicting the Risk of Distant Metastasis in Breast Cancer Using AI-Generated Spatial Pathological Maps (ARGUS project)

February 11, 2026 updated by: Second Affiliated Hospital, School of Medicine, Zhejiang University

The goal of this observational study is to develop and validate an artificial intelligence (AI) model for predicting the risk of distant metastasis in patients with primary breast cancer. The main question it aims to answer is:

Can a multimodal AI model, trained on routinely available histopathological images, accurately predict the long-term risk of breast cancer metastasis?

Researchers will analyze existing hematoxylin and eosin (H&E) and immunohistochemistry (IHC) stained tissue slides from patients who underwent surgery between 2015 and 2025. Clinical data will be used to train the AI model and evaluate its performance in predicting metastasis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Jilin
      • Changchun, Jilin, China, 130000
        • Not yet recruiting
        • Jilin Cancer Hospital
        • Contact:
    • Tianjin Municipality
      • Tianjin, Tianjin Municipality, China, 300060
        • Not yet recruiting
        • Cancer Institute and Hospital, Tianjin Medical University, China
        • Contact:
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • 2nd Affiliated Hospital, School of Medicine, Zhejiang University, China
        • Contact:
      • Hangzhou, Zhejiang, China
        • Not yet recruiting
        • The Fourth Affiliated Hospital of Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

The study participants will be selected from a case-control cohort of adult female patients diagnosed with primary invasive breast cancer who underwent curative surgery at participating centers (e.g., The Second Affiliated Hospital of Zhejiang University) between January 2015 and December 2025.

Eligible individuals must have available, high-quality archived primary tumor tissue samples, specifically H&E-stained whole-slide images and consecutive sections for multiplex immunohistochemistry, coupled with complete clinicopathological data and long-term follow-up information documenting distant metastasis status.

The final study sample will consist of patients from this source population who meet all predefined inclusion and exclusion criteria, ensuring data integrity and cohort homogeneity for AI model development.

Description

Inclusion Criteria:

  1. Female patients aged 18 years or older.
  2. Histologically confirmed primary invasive breast carcinoma.
  3. Underwent curative surgical resection (mastectomy or breast-conserving surgery) between January 2015 and December 2025.
  4. Before initiating the neoadjuvant therapy, there was a retention of the primary tumor specimen.
  5. Availability of high-quality, digitizable Hematoxylin and Eosin (H&E) stained whole-slide images (WSIs).
  6. Availability of consecutive tissue sections from the same tumor block for multiplex immunohistochemistry (mIHC) staining (including markers such as Pan-CK, CD3, CD20).
  7. Complete clinicopathological data and follow-up information must be available, including but not limited to: TNM stage, histological grade, molecular subtype (ER, PR, HER2 status), adjuvant treatment records, and clearly documented distant metastasis-free survival (DMFS) data.
  8. A minimum follow-up of 5 years for patients with detailed information for distant metastasis events.

Exclusion Criteria:

  1. Pure ductal carcinoma in situ (DCIS) without an invasive component.
  2. Special histological subtypes of invasive carcinoma (e.g., metaplastic carcinoma) with distinct biological behaviors.
  3. No original lesion samples were retained before neoadjuvant therapy.
  4. Presence of contralateral breast cancer or a history of any other prior malignancy (except for cured non-melanoma skin cancer or carcinoma in situ of the cervix).
  5. H&E or IHC slides with significant technical artifacts (e.g., fading, folds, heavy knife marks, tissue tearing, uneven staining) that preclude reliable image analysis.
  6. Low tumor cellularity (e.g., tumor area < 10% in the scanned field of view).
  7. Unavailable or unalignable consecutive tissue sections, preventing spatial registration of H&E and mIHC images.
  8. Lack of essential clinicopathological or follow-up data required for model training or validation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Patients with primary breast cancer who have experienced distant metastasis outcomes within 5 years
Other: Diagnostic Test: AI-Based Spatial Pathomic Analysis
This is an observational study with no therapeutic or procedural interventions. The "intervention" refers to the analytical method applied to existing data. Archived tissue samples (H&E and IHC stained slides) will be digitally scanned and analyzed by a multimodal artificial intelligence (AI) model to develop a risk prediction tool for distant metastasis. Patients' clinical data will be collected for model training and validation. No direct interaction with patients occurs, and no treatment decisions are influenced by this study.
Patients with primary breast cancer who have not experienced distant metastasis for at least 5 years
Other: Diagnostic Test: AI-Based Spatial Pathomic Analysis
This is an observational study with no therapeutic or procedural interventions. The "intervention" refers to the analytical method applied to existing data. Archived tissue samples (H&E and IHC stained slides) will be digitally scanned and analyzed by a multimodal artificial intelligence (AI) model to develop a risk prediction tool for distant metastasis. Patients' clinical data will be collected for model training and validation. No direct interaction with patients occurs, and no treatment decisions are influenced by this study.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Predictive accuracy for distant metastasis risk assessed by Time-dependent Area Under the Receiver Operating Characteristic Curve (Time-dependent AUC)
Time Frame: From the date of initial surgery up to 5 years post-operatively, with the occurrence of distant metastasis defined as the event of interest.
The Area Under the Receiver Operating Characteristic Curve (AUC) will be used to evaluate the model's binary classification performance in discriminating between patients with and without distant metastasis at the 5-year post-operative time point. This metric reflects the model's classification accuracy at a specific time.
From the date of initial surgery up to 5 years post-operatively, with the occurrence of distant metastasis defined as the event of interest.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sensitivity and Specificity
Time Frame: Assessed at the 5-year post-operative time point.
Sensitivity and Specificity will be calculated at the optimal cut-off point of the model's risk score to evaluate its binary classification performance. Sensitivity measures the model's ability to correctly identify patients who develop distant metastasis (true positive rate), while Specificity measures its ability to correctly identify patients who do not (true negative rate).
Assessed at the 5-year post-operative time point.
Concordance Index (C-index)
Time Frame: From the time of the initial surgical treatment until distant metastasis occurs or until the end of the follow-up (the longest duration can be up to 10 years).
Harrell's Concordance Index (C-index) will be employed to assess the model's overall prognostic discrimination ability throughout the follow-up period. It evaluates the consistency of the model's risk scores in correctly ranking the time to distant metastasis-free survival among individual patients.
From the time of the initial surgical treatment until distant metastasis occurs or until the end of the follow-up (the longest duration can be up to 10 years).
Model calibration assessed by calibration curve
Time Frame: From the time of the initial surgical treatment until distant metastasis occurs or until the end of the follow-up (the longest duration can be up to 10 years).
The agreement between the model-predicted probability of distant metastasis and the observed actual incidence will be visualized and assessed using a calibration curve.
From the time of the initial surgical treatment until distant metastasis occurs or until the end of the follow-up (the longest duration can be up to 10 years).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 15, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 7, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 24, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2025-1104

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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