Diagnostic Accuracy of PD-L1 Immunohistochemistry Evaluation in Triple Negative Breast Cancer Biopsy

Background: Programmed Death-Ligand 1 (PD-L1) evaluation is essential for predicting response to immune checkpoint inhibitors in advanced Triple-Negative Breast Cancer (TNBC) and determining eligibility for immunotherapy. However, spatial intratumoral heterogeneity raises concerns regarding the representativeness of PD-L1 assessment performed on core needle biopsies (CNBs), potentially leading to the exclusion of eligible patients from effective treatments. Methods:We compared the concordance of PD-L1 expression between CNBs and matched surgical specimens in a TNBC cohort. Immunohistochemical (IHC) evaluations were conducted using the SP142 clone evaluated with the immune cell (IC) score (the atezolizumab eligibility test) and the E1L3N clone, as a surrogate of the 22C3 clone, valuated with the combined positive score (CPS) (the pembrolizumab eligibility test). Additionally, we developed two novel selection methods to identify the optimal IHC protocol for E1L3N staining. Results:The analysis confirmed that PD-L1 expression is frequently underestimated on CNBs compared to surgical specimens. Agreement was "fair" (κ = 0.371) for the SP142 clone (IC score) and "substantial" (κ = 0.610) for the E1L3N clone (CPS). Notably, applying the IC score to the E1L3N clone on biopsy specimens yielded a high Negative Predictive Value (NPV) of 93.3% for predicting SP142/IC status, and an NPV of 100% for predicting E1L3N/CPS status. Conclusions:PD-L1 assessment limited to CNB presents significant challenges in TNBC, particularly with the SP142 assay, due to a high rate of false-negative results that may preclude access to immunotherapy. Our findings suggest that the E1L3N clone (assessed via IC score) could serve as an effective "rule-out" screening test on biopsy material. However, in cases of negative biopsy results, we suggest testing all available archival TNBC tissue and considering a re-biopsy of the primary and metastatic tumor to ensure appropriate therapeutic stratification.