An observational study in Breast Cancer and Nipple Discharge, sponsored by Hubei Cancer Hospital. Recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-17.
Sponsored by Hubei Cancer Hospital · Observational
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.
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's planned enrollment of 60 is below the median of 184 across 3,235 observational studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Hubei Cancer Hospital is the lead sponsor of 25 studies on the registry; 17 are open to participants now.
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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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
Time frame: From preoperative sampling to receipt of final surgical pathology (per participant); primary analysis at validation lock (≈0-3 months post-enrollment).
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.
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)
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.
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)
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.
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)
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.
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
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.
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
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.
Time frame: Baseline (Day 0): sample collection; laboratory QC and adequacy assessed up to 14 days post-collection.
Differential genomic and methylation features associated with malignancy
Number and list of significant copy-number variation (CNV) regions, fragmentomic indices, and differentially methylated regions (DMRs) that distinguish malignant vs benign, declared at FDR \< 0.05; report effect sizes (e.g., log2 fold-change or odds ratios) with 95% confidence intervals. Features derived from baseline biospecimens in the training cohort. Reference standard: final surgical pathology.
Time frame: Baseline (Day 0): preoperative biospecimen collection; analysis completed within 30 days post-collection; summarized at study completion (database lock), an average of 12 months.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: 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.
Started Dec 2025 (actual). Primary completion is estimated for Jun 2027, 18 months after the start.
Of 1,191 non-industry observational studies under Breast Neoplasms, half reached primary completion within 58 months of starting (the median), counting those still running; a quarter within 25 and three quarters within 139. This study's planned 18 months is below that.
Counting every sponsor, half of 1,380 studies reached it within 55 months; a quarter within 25 and three quarters within 126.
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Hubei Cancer Hospital