Abstract
BACKGROUND: Malignant phyllodes tumor of the breast (MPTB) is a rare interstitial neoplasm, accounting for less than 1% of all types of breast tumors. It has the tendency for local recurrence and distant metastasis compared to benign PTB. A number of patients with MPTB experience repeated recurrences, which are associated with dismal long-term survival. Therefore, there is an urgent need to screen out MPTB patients with poor prognosis and implement intensified treatment in early stage. However, there is no biomarkers available to predict prognosis accurately so far. METHODS: We retrospectively collected patients with MPTB between January 2010 and December 2023 across three institutions. Clinicopathological features and follow-up findings were collected and evaluated. The Ki-67 cut‑off was determined using maximally selected rank statistics. Survival outcomes were assessed using Kaplan‑Meier analysis. Univariate and multivariate Cox regression with Firth’s penalized likelihood correction was applied to disease-free survival (DFS) and overall survival (OS) to adjust for potential biases related to cohort size and event rates. RESULTS: A total of 125 patients were included in the study with a median follow-up of 64.0 months. As of 31st October, 2024, 53 patients developed local recurrences, 35 had distant metastases and 24 died. Ki-67 index was demonstrated to be an independent prognostic factor for MPTB with the cut-off value of 30%. Kaplan-Meier analysis revealed that high Ki-67 expression was significantly associated with worse overall survival (P < 0.001) and showed a non-significant trend toward shorter DFS (P = 0.154). Notably, multivariate Cox analysis identified high Ki-67 expression as an independent predictor of shorter OS (HR = 3.66, 95% CI = 1.17–11.47; P = 0.026). Besides, diagnosed at older age and received adjuvant radiotherapy were identified as independent protective factors for DFS, with p-values of 0.014, and 0.011 in the multivariate analysis, respectively. CONCLUSIONS: Elevated Ki-67 expression (>30%) identifies a high-risk subset of MPTB patients with poorer survival. This supports future prospective trials investigating whether intensified management can improve outcomes in this population.