Abstract 4977: Programmed cell death ligand 1 (PD-L1) expression across molecular subtypes of human high-grade ductal carcinoma in situ (DCIS) of the breast

Abstract Background: The expression of PD-L1 in tumor-infiltrating lymphocytes (TILs) in tumor microenvironment (TME) of high-grade breast DCIS is currently unknown. Methods: Formalin-fixed paraffin-embedded specimens from 494 female patients diagnosed with DCIS between 1996-2018 were available to routine diagnostic immunohistochemical (IHC) staining. ER and PR IHC positivity was defined as ≥1% positive tumor cells, and HER2 IHC was scored based on the updated guidelines of the American Society of Clinical Oncology and the College of American Pathologists, as in routine diagnostic procedures. HER2 silver in situ hybridization was performed when the IHC score was 2+. We calculated the Ki67 ratio by counting 200 intraductal epithelial cells in two separate hotspot foci. DCIS cases were classified as Luminal A (LumA), LumB HER2ˉ, LumB HER2+, HER2-enriched, or triple-negative (TPN) subtypes according to the 2013 St. Gallen guidelines, which is used for molecular subtyping of invasive breast carcinoma. Each subtype was sorted into “Pure”: without an invasive component and “W/invasive”: with an invasive component. We calculated the PD-L1 IHC ratio by counting (up to) 1000 immune cells divided by positive PD-L1 cells. PD-L1 expression was dichotomized at a threshold of 1%. We assessed the associations between PD-L1 status, subtype, and other variables, including age, Ki67, DCIS extension, and invasiveness. Results: We identified a significant proportion of TILs in 149/484 (31%) cases. 100% of these cases were high-grade DCIS. We successfully stained 118/149 cases with PD-L1 IHC, and 73/118 (63%) expressed PD-L1 ≥1%. In 92/149 (62%) cases with TILs, strong membrane-positive HER2 overexpression was observed (25% LumB HER2+ and 37% HER2-enriched subtype, p 0.0001). A significant number (31/60; 52%) of the “W/invasive” cases contained TILs, compared to “Pure” (118/362; 32%) (p 0.0055). PD-L1 ≥1% was most prevalent in HER2-enriched (48.6%) and LumB HER2+ (25%) subtypes, with lower representation in LumA (12.5%), LumB HER2ˉ (9.7%), and TPN (4.2%) subtypes. However, comparison of the PD-L1 ≥1% status across subtypes yielded a non-significant chi-square result (p = 0.2734). PD-L1 expression was not significantly associated with “W/invasive” cases (p = 0.0765). Significant differences were observed across subtypes among cases expressing PD-L1 ≥1% for Ki67 (p = 0.0325) and DCIS extension (p = 0.0323), but not for age (p = 0.4329) or invasive status (p = 0.6722). Conclusions: PD-L1 ≥1% was more common in HER2-driven subtypes, but its distribution was not subtype-dependent. PD-L1 expression also lacked a significant association with invasiveness. These findings demonstrated strong PD-L1 expression in high-grade DCIS, although the utility of PD-L1 as a standalone biomarker for subtype stratification or prediction of invasive potential in DCIS patients could be limited. Citation Format: Hossein Schandiz, Lorant Farkas, Berit Gravdehaug, Elin Edda Seland Agustsdottir, Torill Sauer, Jürgen Geisler. Programmed cell death ligand 1 (PD-L1) expression across molecular subtypes of human high-grade ductal carcinoma in situ (DCIS) of the breast abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4977.