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

Inclusion Criteria: 1. Age ≥18 years. 2. Spontaneous, unilateral, single-duct pathologic nipple discharge, predominantly bloody or serosanguinous, raising clinical suspicion of intraductal disease. 3. 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. 4. Study sampling (nipple discharge and one peripheral blood tube) feasible before surgery/invasive diagnostics without delaying standard care. 5. Able and willing to provide written informed consent and allow access to surgical pathology and relevant clinical data. Exclusion Criteria: 1. Physiologic or non-pathologic discharge (typically bilateral, multiduct, expressible only with manipulation; milky/clear/green) or galactorrhea due to endocrine/drug causes. 2. Active breast infection/inflammatory disease (e.g., abscess) as the source of discharge. 3. Prior diagnosis and treatment of breast cancer (surgery/radiation/systemic therapy). 4. Recent invasive ductal manipulation likely to confound analysis (e.g., ductoscopy, duct cannulation/irrigation), per investigator judgment. 5. Pregnant or lactating patients. 6. Significant hematologic disease/coagulopathy precluding safe sampling. 7. Inability to complete preoperative study sampling, refusal/withdrawal of consent, or poor compliance. 8. Any condition judged by investigators to compromise sample quality, data interpretation, or participant safety.