Breast CancerNCT07250204
A Study on Combined Low-pass Whole-genome and Methylome Testing of Bloody Nipple Discharge Specimens for Benign-Malignant Differentiation.
An observational study of Breast Cancer and Nipple Discharge, run by Hubei Cancer Hospital at 1 site in China.
Trial summary
This is a prospective, single-center diagnostic study testing whether a new, minimally invasive analysis of nipple fluid can distinguish benign from malignant causes of pathologic nipple discharge. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Nipple Discharge
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 21 Dec 2025to Aug 2027
- How long will I take part?
- 1 Month
- 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: Prospective, single-center consecutive series at Hubei Cancer Hospital. Adults presenting with spontaneous, unilateral, single-duct bloody/serosanguinous nipple discharge and scheduled for diagnostic surgery/biopsy will undergo preoperative nipple-discharge collection for low-coverage whole-genome sequencing and methylome profiling. Postoperative pathology serves as the gold standard to classify benign vs malignant lesions. Enrollment is not restricted by gender identity; individuals with relevant breast anatomy who meet criteria may be included. Excludes physiologic discharge, infection, prior treated breast cancer, pregnancy/lactation, recent duct manipulation, and unsafe sampling conditions. Target sample size ≈30; no healthy volunteers.
Who may be able to join
- Age ≥18 years.
- Spontaneous, unilateral, single-duct pathologic nipple discharge, predominantly bloody or serosanguinous, raising clinical suspicion of intraductal disease.
- Planned diagnostic breast surgery/biopsy after specialist assessment (e.g., duct excision/microdochectomy, lumpectomy); patients who had ductoscopy but are still scheduled for surgery remain eligible.
- Study sampling (nipple discharge and one peripheral blood tube) feasible before surgery/invasive diagnostics without delaying standard care.
- Able and willing to provide written informed consent and allow access to surgical pathology and relevant clinical data.
Who cannot join
- Physiologic or non-pathologic discharge (typically bilateral, multiduct, expressible only with manipulation; milky/clear/green) or galactorrhea due to endocrine/drug causes.
- Active breast infection/inflammatory disease (e.g., abscess) as the source of discharge.
- Prior diagnosis and treatment of breast cancer (surgery/radiation/systemic therapy).
- Recent invasive ductal manipulation likely to confound analysis (e.g., ductoscopy, duct cannulation/irrigation), per investigator judgment.
- Pregnant or lactating patients.
- Significant hematologic disease/coagulopathy precluding safe sampling.
- Inability to complete preoperative study sampling, refusal/withdrawal of consent, or poor compliance.
- Any condition judged by investigators to compromise sample quality, data interpretation, or participant safety.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
This is a prospective, single-center diagnostic study testing whether a new, minimally invasive analysis of nipple fluid can distinguish benign from malignant causes of pathologic nipple discharge. Many patients with bloody or blood-tinged nipple discharge undergo surgery to make a diagnosis, yet most are ultimately found to have benign disease. The investigators aim to develop a laboratory test that analyzes DNA in nipple fluid to help avoid unnecessary operations while still identifying cancers.
Approximately 30 adults with spontaneous, single-duct, unilateral bloody or serosanguinous nipple discharge who are already scheduled for standard diagnostic surgery will be enrolled at Hubei Cancer Hospital. Before surgery, the investigators will collect a small sample of nipple fluid (or gently obtain nipple aspirate fluid using a soft suction cup if needed) and one tube of blood. The investigators will analyze the fluid's DNA using two approaches: low-pass whole-genome analysis to look for copy number changes and fragmentation patterns, and genome-wide DNA methylation profiling. Surgical pathology will serve as the reference standard. Using these data, the investigators will build and validate a model to classify lesions as benign or malignant.
The primary outcome is diagnostic accuracy (area under the ROC curve, sensitivity, and specificity). Secondary outcomes include positive and negative predictive values, model calibration, subgroup performance (e.g., ductal carcinoma in situ vs invasive cancer), and an estimate of potential clinical impact (for example, how many benign cases might safely avoid surgery at a high-sensitivity threshold). Study test results will not affect current clinical care; all participants will receive usual evaluation and surgery. Risks are minimal and may include brief nipple discomfort or skin irritation from gentle suction and routine blood-draw risks (bruising, lightheadedness). There is no direct benefit to participants, but the findings may support a future noninvasive test to guide care and reduce unnecessary surgery. Data will be de-identified and stored securely. Expected enrollment is from September 2025 to May 2026.
- Conditions
- Breast Cancer, Nipple Discharge
- Keywords
- Nipple Discharge, Bloody nipple discharge, Nipple aspirate fluid (NAF), Pathologic nipple discharge (PND), Breast cancer
- Medical subject headings
- Breast Neoplasms, Galactorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Malignant Cohort - Pathologic Nipple Discharge (DCIS/IDC) | Adults (≥18 years) with unilateral, spontaneous, single-duct pathologic nipple discharge who undergo clinically indicated diagnostic surgery. Group assignment is based on postoperative breast pathology confirming malignant disease (e.g., ductal carcinoma in situ or invasive ductal carcinoma). Preoperative nipple discharge is collected for low-coverage whole-genome sequencing (fragmentomics/CNV) and genome-wide DNA methylation profiling. Usual care only; research testing does not alter management. Followed through surgery and receipt of final pathology; no protocol-mandated long-term follow-up. | |
| Benign Cohort - Pathologic Nipple Discharge (Papilloma/Duct Ectasia) | Adults (≥18 years) with unilateral, spontaneous, single-duct pathologic nipple discharge who undergo clinically indicated diagnostic surgery. Group assignment is based on postoperative breast pathology confirming benign disease (e.g., intraductal papilloma, duct ectasia, other benign lesions). Preoperative nipple discharge is collected for low-coverage whole-genome sequencing (fragmentomics/CNV) and genome-wide DNA methylation profiling. Usual care only; research testing does not alter management. Followed through surgery and receipt of final pathology; no protocol-mandated long-term follow-up. |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC of the combined lcWGS-methylome model for distinguishing malignant vs benign lesions
Area under the ROC curve (AUC) with 95% CI in the independent validation cohort. Reference standard is postoperative pathology. Model integrates preoperative nipple discharge features (CNV/fragmentomics from low-coverage WGS and genome-wide DNA methylation) with a locked threshold selected on training.
Measured: From preoperative sampling to receipt of final surgical pathology (per participant); primary analysis at validation lock (≈0-3 months post-enrollment).
Secondary outcomes (6)
Sensitivity and specificity at a prespecified threshold (target sensitivity ≥95%)
Sensitivity (true positive rate) and specificity (true negative rate), with 95% confidence intervals, estimated in the independent validation cohort at a threshold fixed on the training set to target ≥95% sensitivity. Surgical pathology is the reference standard.
Measured: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Positive and negative predictive values (PPV, NPV)
PPV and NPV, with 95% confidence intervals, calculated in the independent validation cohort at the prespecified decision threshold, using surgical pathology as the reference standard.
Measured: preoperative sampling (Day 0); outcome assessed at final surgical pathology, up to 30 days after surgery.
Model calibration (calibration slope, intercept, and Hosmer-Lemeshow test)
Agreement between predicted probabilities and observed outcomes in the independent validation cohort; report calibration slope and intercept (with 95% confidence intervals) from logistic calibration, and Hosmer-Lemeshow goodness-of-fit p-value (by deciles). Reference standard: final surgical pathology.
Measured: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Proportion of model-negative results in benign cases at a prespecified decision threshold (independent validation cohort)
Among participants with benign final surgical pathology, calculate the proportion with a model-negative result when applying a decision threshold prespecified on the training set to achieve >=95% sensitivity for malignancy. Report the percentage and 95% confidence interval. Reference standard: final surgical pathology.
Measured: Preoperative sampling (Day 0); outcome assessed at the time of the final surgical pathology report, up to 30 days postoperatively.
Subgroup performance by pathology subtype and imaging status
Area under the ROC curve (AUC), sensitivity, and specificity (with 95% confidence intervals) in the independent validation cohort, stratified by pathology subtype (DCIS vs IDC) and by presence vs absence of preoperative imaging abnormalities (mammography/ultrasound/MRI). Sensitivity and specificity estimated at a prespecified threshold fixed on the training set to target ≥95% sensitivity. Reference standard: final surgical pathology.
Measured: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Technical success rate and sample adequacy
Proportion of nipple discharge samples yielding sequencing libraries that pass prespecified QC thresholds and are analyzable; report percentage and 95% confidence interval. Summarize cfDNA yield (ng) and sequencing depth metrics (aligned reads and mean unique coverage) with medians and interquartile ranges.
Measured: Baseline (Day 0): sample collection; laboratory QC and adequacy assessed up to 14 days post-collection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2025
- Study start21 Dec 2025
- Primary completionJun 2027 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 60 participants (estimated)
- Target duration
- 1 Month
Sponsor and investigators
- Lead sponsor
- Hubei Cancer Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xinhong Wu, PhD, Hubei Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07250204
- Sponsor's protocol ID
- LLHBCH2025YN-072
- Status last verified
- Sep 2025
- First submitted
- 19 Sep 2025
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: We do not plan to share individual participant data (IPD). The informed consent for this study and institutional/regulatory constraints do not permit external sharing of participant-level datasets. Aggregate results will be posted on ClinicalTrials.gov and reported in peer-reviewed publications. The study protocol, statistical analysis plan, and a CSR synopsis will be made available upon publication.
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study on Combined Low-pass Whole-genome and Methylome Testing of Bloody Nipple Discharge Specimens for Benign-Malignant Differentiation.
- ClinicalTrials.gov ID
- NCT07250204
- Acronym / sponsor ID
- LLHBCH2025YN-072
- Conditions
- Breast Cancer, Nipple Discharge
- Keywords
- Nipple Discharge, Bloody nipple discharge, Nipple aspirate fluid (NAF), Pathologic nipple discharge (PND), Breast cancer
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Hubei Cancer HospitalUniversity, hospital or other
- Study start
- 21 Dec 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 26 Nov 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.
This is a prospective, single-center diagnostic study testing whether a new, minimally invasive analysis of nipple fluid can distinguish benign from malignant causes of pathologic nipple discharge. Many patients with bloody or blood-tinged nipple discharge undergo surgery to make a diagnosis, yet most are ultimately found to have benign disease. The investigators aim to develop a laboratory test that analyzes DNA in nipple fluid to help avoid unnecessary operations while still identifying cancers.
Approximately 30 adults with spontaneous, single-duct, unilateral bloody or serosanguinous nipple discharge who are already scheduled for standard diagnostic surgery will be enrolled at Hubei Cancer Hospital. Before surgery, the investigators will collect a small sample of nipple fluid (or gently obtain nipple aspirate fluid using a soft suction cup if needed) and one tube of blood. The investigators will analyze the fluid's DNA using two approaches: low-pass whole-genome analysis to look for copy number changes and fragmentation patterns, and genome-wide DNA methylation profiling. Surgical pathology will serve as the reference standard. Using these data, the investigators will build and validate a model to classify lesions as benign or malignant.
The primary outcome is diagnostic accuracy (area under the ROC curve, sensitivity, and specificity). Secondary outcomes include positive and negative predictive values, model calibration, subgroup performance (e.g., ductal carcinoma in situ vs invasive cancer), and an estimate of potential clinical impact (for example, how many benign cases might safely avoid surgery at a high-sensitivity threshold). Study test results will not affect current clinical care; all participants will receive usual evaluation and surgery. Risks are minimal and may include brief nipple discomfort or skin irritation from gentle suction and routine blood-draw risks (bruising, lightheadedness). There is no direct benefit to participants, but the findings may support a future noninvasive test to guide care and reduce unnecessary surgery. Data will be de-identified and stored securely. Expected enrollment is from September 2025 to May 2026.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 1 Month
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Malignant Cohort - Pathologic Nipple Discharge (DCIS/IDC) | – | –Adults (≥18 years) with unilateral, spontaneous, single-duct pathologic nipple discharge who undergo clinically indicated diagnostic surgery. Group assignment is based on postoperative breast pathology confirming malignant disease (e.g., ductal carcinoma in situ or invasive ductal carcinoma). Preoperative nipple discharge is collected for low-coverage whole-genome sequencing (fragmentomics/CNV) and genome-wide DNA methylation profiling. Usual care only; research testing does not alter management. Followed through surgery and receipt of final pathology; no protocol-mandated long-term follow-up. |
| Benign Cohort - Pathologic Nipple Discharge (Papilloma/Duct Ectasia) | – | –Adults (≥18 years) with unilateral, spontaneous, single-duct pathologic nipple discharge who undergo clinically indicated diagnostic surgery. Group assignment is based on postoperative breast pathology confirming benign disease (e.g., intraductal papilloma, duct ectasia, other benign lesions). Preoperative nipple discharge is collected for low-coverage whole-genome sequencing (fragmentomics/CNV) and genome-wide DNA methylation profiling. Usual care only; research testing does not alter management. Followed through surgery and receipt of final pathology; no protocol-mandated long-term follow-up. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Prospective, single-center consecutive series at Hubei Cancer Hospital. Adults presenting with spontaneous, unilateral, single-duct bloody/serosanguinous nipple discharge and scheduled for diagnostic surgery/biopsy will undergo preoperative nipple-discharge collection for low-coverage whole-genome sequencing and methylome profiling. Postoperative pathology serves as the gold standard to classify benign vs malignant lesions. Enrollment is not restricted by gender identity; individuals with relevant breast anatomy who meet criteria may be included. Excludes physiologic discharge, infection, prior treated breast cancer, pregnancy/lactation, recent duct manipulation, and unsafe sampling conditions. Target sample size ≈30; no healthy volunteers.
Key inclusion criteria (5 listed)
- Age ≥18 years.
- Spontaneous, unilateral, single-duct pathologic nipple discharge, predominantly bloody or serosanguinous, raising clinical suspicion of intraductal disease.
- Planned diagnostic breast surgery/biopsy after specialist assessment (e.g., duct excision/microdochectomy, lumpectomy); patients who had ductoscopy but are still scheduled for surgery remain eligible.
- Study sampling (nipple discharge and one peripheral blood tube) feasible before surgery/invasive diagnostics without delaying standard care.
- Able and willing to provide written informed consent and allow access to surgical pathology and relevant clinical data.
Key exclusion criteria (8 listed)
- Physiologic or non-pathologic discharge (typically bilateral, multiduct, expressible only with manipulation; milky/clear/green) or galactorrhea due to endocrine/drug causes.
- Active breast infection/inflammatory disease (e.g., abscess) as the source of discharge.
- Prior diagnosis and treatment of breast cancer (surgery/radiation/systemic therapy).
- Recent invasive ductal manipulation likely to confound analysis (e.g., ductoscopy, duct cannulation/irrigation), per investigator judgment.
- Pregnant or lactating patients.
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
AUC of the combined lcWGS-methylome model for distinguishing malignant vs benign lesions
Time frame: From preoperative sampling to receipt of final surgical pathology (per participant); primary analysis at validation lock (≈0-3 months post-enrollment).
Area under the ROC curve (AUC) with 95% CI in the independent validation cohort. Reference standard is postoperative pathology. Model integrates preoperative nipple discharge features (CNV/fragmentomics from low-coverage WGS and genome-wide DNA methylation) with a locked threshold selected on training.
6 secondary outcomes
Sensitivity and specificity at a prespecified threshold (target sensitivity ≥95%)
Time frame: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Positive and negative predictive values (PPV, NPV)
Time frame: preoperative sampling (Day 0); outcome assessed at final surgical pathology, up to 30 days after surgery.
Model calibration (calibration slope, intercept, and Hosmer-Lemeshow test)
Time frame: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Proportion of model-negative results in benign cases at a prespecified decision threshold (independent validation cohort)
Time frame: Preoperative sampling (Day 0); outcome assessed at the time of the final surgical pathology report, up to 30 days postoperatively.
Subgroup performance by pathology subtype and imaging status
Time frame: Perioperative/Periprocedural: preoperative sampling (Day 0); outcome assessed at final surgical pathology report, up to 30 days postoperatively.
Technical success rate and sample adequacy
Time frame: Baseline (Day 0): sample collection; laboratory QC and adequacy assessed up to 14 days post-collection.
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 17 Jul 2026.
- Individual participant dataSharing planned: No. We do not plan to share individual participant data (IPD). The informed consent for this study and institutional/regulatory constraints do not permit external sharing of participant-level datasets. Aggregate results will be posted on ClinicalTrials.gov and reported in peer-reviewed publications. The study protocol, statistical analysis plan, and a CSR synopsis will be made available upon publication.
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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 Nipple Discharge, run by Hubei Cancer Hospital 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 5 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 17 Jul 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 Xinhong Wu Principal Investigator (+8618602726300, wuxinhong_9@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AUC of the combined lcWGS-methylome model for distinguishing malignant vs benign lesions (time frame: From preoperative sampling to receipt of final surgical pathology (per participant); primary analysis at validation lock (≈0-3 months post-enrollment).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jul 2026.