62P Evaluation of alternative prognostic thresholds for SP142 and 22C3 immunohistochemical PD-L1 expression in triple-negative breast cancer: Results from a population-based cohort

Immune checkpoint inhibitors are now a part of the treatment arsenal for triple-negative breast cancer (TNBC) but refinement of PD-L1 as a prognostic and predictive biomarker in TNBC is a clinical priority. We aimed to evaluate the relevance of novel PD-L1 immunohistochemical (IHC) thresholds with regards to prognostic value, PD-L1 gene expression and TNBC molecular subtypes. We evaluated PD-L1 on a tissue microarray with the SP142 (immune cell score; IC) and 22C3 (combined positive score; CPS) IHC assays and scored abundance of TILs on H CPS ≥1) was significantly associated with better prognosis compared to zero PD-L1 expression. Importantly however, also patients with intermediate expression (IC >0%, 0, <1) showed a trend towards improved outcome for all the endpoints. Tumors with intermediate IHC expression also had intermediate PD-L1 (CD274) gene expression (mRNA). Patients low in TILs (<30%) and PD-L1 tended to have the poorest prognosis. PD-L1 positive tumors clustered significantly more often as Immunomodulatory-high and Basal-Like 1-high TNBC subtypes. PD-L1-zero tumors were more prevalently of the Luminal-Androgen-Receptor-high, Mesenchymal-high and Mesenchymal Stem-like-high molecular subtypes. PD-L1-intermediate tumors categorized with neither PD-L1-positive nor PD-L1-zero tumors on the hierarchical clustering level, forming thus a unique subgroup. With both SP142 and 22C3, we identified an intermediate IHC PD-L1 group within TNBCs that was supported on the molecular level. Any PD-L1 IHC expression, even though it is <1, tended to have positive prognostic impact. We suggest that the generally accepted threshold of PD-L1 IHC positivity in TNBC should be investigated further.