Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

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Title
Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer
Author(s)
S G Ahn; Seon-Kyu Kim; J H Shepherd; Y J Cha; S J Bae; C Kim; J Jeong; C M Perou
Bibliographic Citation
Breast Cancer Research and Treatment, vol. 188, no. 1, pp. 165-178
Publication Year
2021
Abstract
Purpose: The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods: Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results: Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions: We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.
Keyword
Triple-negative breast cancerSP142 PD-L1Tumor-infltrating lymphocytesImmune-check point inhibitors
ISSN
0167-6806
Publisher
Springer
DOI
http://dx.doi.org/10.1007/s10549-021-06193-9
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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