Abstract Background. To determine the appropriate surgical margin and identify predictive factors for recurrence and prognosis of borderline and malignant phyllodes tumor (PT) of the breast. Methods. A retrospective review of patients with borderline and malignant PT treated from March 2011 to December 2022 at the First Affiliated Hospital of Chongqing Medical University were conducted. The main endpoints of this research were local recurrence-free survival (LRFS) and disease-free survival (DFS). Univariate and multivariate Cox proportional hazard models were used to examine the impacts of different variables on LRFS and DFS, and to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results. Of 155 patients with phyllodes tumors, 87 (56.1%) were classified as borderline while 68 (43.9%) were malignant. All patients included underwent operation, with a median age of 47 years (range,12-66 years) and a median tumor size of 60 mm (range,15-300 mm). Initial surgical margins < 1cm in 72 (46.5%) patients, of which 28 (38.9%) underwent reoperation, resulting in 45 (28.4%) patients with a margin < 1cm and 111 (71.6%) patients with a margin ≥1cm. At a median follow-up period of 66 months (range 3-146 months), local recurrence was observed in 36 patients (23.2%), and distant metastasis occurred in 10 patients (6.5%). In this cohort, the rates of 5-year LRFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin < 1 cm group (83.8% vs 50.4%, log-rank P< 0.001), both for the borderline (log-rank P=0.010) and the malignant PT (log-rank P< 0.001).Similarly, for both borderline (log-rank P=0.019) and malignant PT (log-rank P< 0.001), the rates of 5-year DFS was significantly higher in the surgical margin ≥1 cm group than in the surgical margin < 1 cm group (80.3% vs 47.5%, log-rank P=0.002). For 72 patients with the initial margin < 1 cm, 5-year DFS for undergoing reoperation to achieve a margin ≥1 cm and remaining with a margin < 1 cm were84.1% and 47.5%, respectively (P=0.008). In univariate analysis of the entire cohort, age, fibroadenoma surgery history, surgical methods, and surgical margins emerged as predictive factors for LRFS (P=0,003, 0.019, 0.026, and0.001, respectively), whereas age, reproductive history, fibroadenoma surgery history, tumor size and surgical margins were predictors of DFS (P= 0,011, 0.025, 0.039, 0.022, and0.002, respectively).In multivariate analysis, age< 45 years (HR=2.186, 95%CI:1.105-4.328, P=0.025)and surgical margins< 1cm (HR=2.181, 95%CI:1.021-4.659, P=0.044) were independent risk factors of LRFS. Independent risk factors for DFS included tumor size>5cm (HR=2.265, 95%CI:1.113-4.606, P=0.024) and surgical margins < 1cm (HR=2.689, 95%CI:1.438-5.027, P=0.002). Conclusion. For borderline and malignant PT, surgical margins of at least 1 cm should be achieved for a better prognosis. Patients aged < 45 years with a high risk of local recurrence and larger tumor patients with poor prognosis, multiple therapy modalities may be required for these high-risk patients. Survival curves for impact of variables on LRFS and DFS Table 1 Univariate and multivariate analysis of LRFS of PTs of the breast (n=155) Table 2 Univariate and multivariate analysis of DFS of PTs of the breast (n=155) Citation Format: lu Gan, Jialin Su. Surgical Margins and prognosis of borderline and malignant phyllodes tumors of breast [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-01.