Dynamic ctDNA Monitoring in Advanced Malignant Phyllodes Tumors of the Breast

Malignant phyllodes tumor of the breast is a rare fibroepithelial tumor. Patients with metastatic or unresectable disease have limited systemic treatment options, and there remains a need for biomarkers that can dynamically reflect disease changes during treatment. Circulating tumor DNA (ctDNA) may provide additional information on tumor burden and disease progression through a minimally invasive blood-based approach. This prospective, multicenter, observational cohort study will enroll approximately 50 patients with advanced malignant phyllodes tumors of the breast who have distant metastases or are currently not candidates for curative surgery and are planning to start systemic therapy. Peripheral blood samples will be collected before treatment and at predefined time points during the current systemic treatment line, including time points corresponding to routine imaging assessments. Individualized tumor-informed ctDNA monitoring panels will be established using patient-specific somatic variants identified from tumor whole-exome sequencing obtained during routine clinical care. The study will primarily evaluate the relationship between dynamic changes in ctDNA during the current systemic treatment line and progression-free survival (PFS), and will explore the potential value of longitudinal ctDNA monitoring for disease monitoring and prognostic assessment in advanced malignant phyllodes tumors. Study ctDNA results will not be used independently to guide clinical treatment decisions.

Inclusion Criteria: * Female patients aged 18 years or older. * Pathologically confirmed malignant phyllodes tumor of the breast. * Distant metastatic disease, or disease considered unsuitable for curative surgery based on multidisciplinary discussion or investigator assessment. * Planning to start the current line of systemic therapy and able to complete baseline ctDNA blood collection and the required baseline assessments before initiation of that treatment line. * At least one lesion available for imaging follow-up and assessment of disease progression. * No prior tumor tissue whole-exome sequencing (WES), with WES independently determined by the treating physician to be clinically indicated based on the patient's own diagnostic and treatment needs; the patient must be able to undergo clinical WES and provide the resulting WES data and the necessary authorized molecular data required for establishment of an individualized ctDNA monitoring panel. * Estimated life expectancy greater than 3 months, with clinical status considered adequate by the investigator to complete study-related blood collection, imaging assessments, and follow-up. * The participant voluntarily agrees to participate in the study and provides written informed consent. Exclusion Criteria: * 1.Insufficient candidate somatic variants available for individualized tracking in the clinical WES results, or molecular data that do not meet the requirements for establishment of an individualized ctDNA monitoring panel. * Presence of another active malignancy that may affect assessment of the study endpoints, except for cured carcinoma in situ, non-melanoma skin cancer, or a prior malignancy judged by the investigator not to affect study endpoint assessment. * Severe active infection, severe cardiac, pulmonary, hepatic, or renal dysfunction, uncontrolled systemic disease, or any other clinical condition that, in the investigator's judgment, makes the patient unsuitable for study participation. * Pregnant or breastfeeding women. * Inability to understand the study, provide informed consent, or comply with follow-up because of psychiatric, cognitive, social, or other factors. * Any other condition that, in the investigator's judgment, makes the patient unsuitable for enrollment. * The current systemic treatment line has already started and baseline ctDNA blood collection could not be completed before initiation of that treatment line.