Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay

Author:

Danziger Natalie1,Sokol Ethan S1,Graf Ryon P1,Hiemenz Matthew C1,Maule Jake1,Parimi Vamsi1,Palmieri Carlo2,Pusztai Lajos3ORCID,Ross Jeffrey S14,Huang Richard S P1ORCID

Affiliation:

1. Foundation Medicine, Inc. , Cambridge, MA , USA

2. Department of Molecular and Clinical Cancer Medicine, University of Liverpool , Liverpool , UK

3. The Clatterbridge Cancer Centre National Health Service (NHS) Foundation Trust , Liverpool , UK

4. Departments of Pathology and Urology, State University of New York Upstate Medical University , Syracuse, NY , USA

Abstract

AbstractBackgroundIn 2020, pembrolizumab was approved as a therapy for triple-negative breast cancer (TNBC) with the companion diagnostic DAKO 22C3 programmed death ligand-1 (PD-L1) immunohistochemistry assay. The study aimed to determine the landscape of PD-L1 expression as detected by the DAKO 22C3 PD-L1 assay in breast cancer subtypes and compare the clinicopathologic and genomic characteristics of PD-L1 positive and negative TNBC.MethodsPD-L1 expression using the DAKO 22C3 antibody was scored using a combined positive score (CPS) and positive status was defined as CPS ≥10. Comprehensive genomic profiling was performed using the FoundationOne CDx assay.ResultsOf the 396 BC patients stained with DAKO 22C3, the majority were HR+/HER2− and TNBC (42% and 36%, respectively). Median PD-L1 expression and frequency of CPS ≥10 was highest in TNBC cases (median: 7.5, 50% CPS ≥10) and lowest in the HR+/HER2− group (median: 1.0, 15.5% CPS ≥10) (P < .0001). A comparison of PD-L1 positive and PD-L1 negative TNBC demonstrated no significant differences in clinicopathologic or genomic characteristics. TNBC tissue samples from the breast did have an observed enrichment for PD-L1 positivity compared to TNBC tissue samples from a metastatic site (57% vs. 44%), but this was not statistically significant (P = .1766). In the HR+/HER2− group, genomic alterations in TP53, CREBBP, and CCNE1 were more prevalent and genomic loss of heterozygosity was higher in the PD-L1(+) group compared to the PD-L1(−) group.ConclusionsThe subtypes of breast cancer have distinct patterns of PD-L1 expression, supporting that further research of immunotherapies may include specific evaluation of optimum cutoffs for non-TNBC patients. In TNBC, PD-L1 positivity is not associated with other clinicopathologic or genomic features and should be integrated into future studies of immunotherapy efficacy.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

Reference43 articles.

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