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

被引:7
作者
Danziger, Natalie [1 ]
Sokol, Ethan S. [1 ]
Graf, Ryon P. [1 ]
Hiemenz, Matthew C. [1 ]
Maule, Jake [1 ]
Parimi, Vamsi [1 ]
Palmieri, Carlo [2 ,3 ]
Pusztai, Lajos [4 ]
Ross, Jeffrey S. [1 ,5 ]
Huang, Richard S. P. [1 ,6 ]
机构
[1] Fdn Med Inc, Cambridge, MA USA
[2] Univ Liverpool, Dept Mol & Clin Canc Med, Liverpool, England
[3] Natl Hlth Serv NHS Fdn Trust, Clatterbridge Canc Ctr, Liverpool, England
[4] Yale Sch Med, Yale Canc Ctr, Breast Med Oncol, New Haven, CT USA
[5] SUNY Upstate Med Univ, Dept Pathol & Urol, Syracuse, NY USA
[6] 150 Second St, Cambridge, MA 02141 USA
关键词
breast cancer; immunotherapy; PD-L1; triple-negative breast cancer; biomarkers; comprehensive genomic profiling; DOUBLE-BLIND; OVARIAN-CARCINOMA; CANCER; RUCAPARIB;
D O I
10.1093/oncolo/oyad025
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The objective of this study was to determine the landscape of PD-L1 protein expression in breast cancer using the DAKO 22C3 assay and to compare PD-L1-positive and PD-L1-negative cancers by comprehensive genomic profiling to determine if these populations differ in clinical or genomic characteristics. 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.
引用
收藏
页码:319 / 326
页数:8
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