Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm, and the role of postoperative radiotherapy (PORT) remains controversial. Our team has previously established a molecular subtyping system for PT, classifying patients into four subtypes. Among them, the malignant novel 1/2 (MN1/MN2) subtypes exhibit extremely high risk of local recurrence, and retrospective data suggest that PORT may significantly improve local control in these subtypes. This study aims to evaluate the efficacy and safety of molecular subtype-guided postoperative radiotherapy (PORT) in patients with MN-subtype phyllodes tumor of the breast. This prospective, multicenter, open-label, randomized controlled trial plans to enroll 160 patients with molecularly confirmed MN1 or MN2 subtype who have undergone R0 resection. Patients will be randomized in a 1:1 ratio to either the PORT group or the observation-only group, with stratification by negative margin width (<1 cm vs. ≥1 cm) and molecular subtype (MN1 vs. MN2). The primary endpoint is 2-year local recurrence-free survival (LRFS). Secondary endpoints include distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), and the incidence of acute and late radiotherapy-related toxicities. By using an innovative molecular subtyping system to precisely select the target population, this study seeks to assess the benefit and safety of PORT in MN-subtype phyllodes tumors. The results are expected to provide the highest level of evidence for this specific subgroup, advance treatment strategies toward "molecular subtype-guided precision radiotherapy," improve patient outcomes, and inform future clinical guidelines.

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years.
2. Histologically confirmed breast phyllodes tumor (PT) by the central laboratory, with molecular classification as MN1 or MN2 subtype via transcriptome sequencing or IHC;
3. Primary or ipsilateral local recurrence following R0 resection (negative margins) before enrollment;
4. Pathologically confirmed borderline or malignant PT;
5. No evidence of distant metastasis (M0);
6. ECOG performance status 0-1;
7. Signed informed consent before treatment;
8. Expected randomization and study entry within 8-12 weeks (no later than 16 weeks) after surgery.

Exclusion Criteria:

1. Previous radiation to the same-side breast or chest;
2. women, or those of childbearing potential refusing effective contraception; Pregnancy, lactation, or refusal of contraception by fertile subjects;
3. Grade III-IV bone marrow suppression: WBC≤1.9*109/L，ANC≤0.9*109/L，PLT≤49*109/L，AST, ALT≥2*ULN;
4. Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF < 50%;
5. Significant diarrhea, severe active infection, uncontrolled systemic disease, interstitial lung disease, active connective tissue disease, or LVEF < 50%;
6. Prior or planned systemic anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, or investigational agents) during the study;
7. Participation in other clinical trials that precludes study inclusion;
8. Any other condition that, in the opinion of the investigator, renders the patient unsuitable for the trial.