A Study on Combined Low-pass Whole-genome and Methylome Testing of Bloody Nipple Discharge Specimens for Benign-Malignant Differentiation.

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.

NCT Number	NCT07250204
Lead Sponsor	Hubei Cancer Hospital
Conditions	Breast Cancer, Nipple Discharge
Enrollment	60 participants
Start Date	2025-12-21
Primary Completion	2027-06 (estimated)
Study Completion	2027-08 (estimated)
Updated on ClinicalTrials.gov	2026-07-17