The Correlation Between PD-L1 Expression in Metaplastic Breast Cancer and Clinical-Pathological Features and...

Background and Objectives: Metaplastic breast carcinoma (MBC) is a rare, aggressive malignancy that is often resistant to conventional chemotherapy and characterized by a triple-negative phenotype. While immune checkpoint inhibition shows promise, the prognostic significance and distribution of programmed death-ligand 1 (PD-L1) expression within the heterogeneous architecture of MBC remain poorly understood. This study aimed to evaluate PD-L1 expression and the density of tumor-infiltrating lymphocytes (TILs) to clarify their roles in patient stratification and overall survival (OS). Materials and Methods: We retrospectively analyzed 48 MBC cases diagnosed between 2010 and 2025. PD-L1 expression was quantified using the Combined Positive Score (CPS) with the 22C3 antibody clone across diverse histological components. The density of stromal TIL density was assessed following internationally standardized guidelines. Clinical outcomes and clinicopathological parameters, including metastasis, lymphovascular invasion (LVI), and histological subtype, were correlated with biomarker status using Kaplan-Meier survival analysis and Cox proportional hazards regression models. Results: PD-L1 positivity (CPS ≥1) was identified in 72.9% of cases, one of the highest rates documented in literature. Notably, an inverse relationship was observed with PD-L1-negative tumors, which exhibited significantly higher rates of distant metastasis (46.2% vs. 17.1%; p = 0.039). Multivariate analysis confirmed that low density of TILs (HR = 9.66; p = 0.016), metastasis (HR = 4.40; p = 0.023), and the presence of LVI (HR = 3.84; p = 0.047) were strong independent predictors of mortality. While PD-L1 status alone did not directly dictate overall survival, mean overall survival was markedly reduced in the low TILs cohort (32.2 months) compared to the high TILs group (114.2 months). Conclusions: The high prevalence of PD-L1 expression supports routine screening for immunotherapy eligibility in MBC. Our findings suggest that PD-L1-negative cases represent a high-risk biological subset driven by alternative immune evasion mechanisms. Integrating TIL density with conventional pathological parameters provides a more robust prognostic framework, enabling personalized therapeutic strategies for this challenging malignancy.