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

Oncologist. 2023 Apr 6;28(4):319-326. doi: 10.1093/oncolo/oyad025.


Background: In 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.

Methods: PD-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.

Results: Of 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.

Conclusions: The 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.

Keywords: PD-L1; biomarkers; breast cancer; comprehensive genomic profiling; immunotherapy; triple-negative breast cancer.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms* / pathology
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / pathology


  • CD274 protein, human
  • B7-H1 Antigen
  • Biomarkers, Tumor