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

Sung Gwe Ahn, Seon Kyu Kim, Jonathan H. Shepherd, Yoon Jin Cha, Soong June Bae, Chungyeul Kim, Joon Jeong, Charles M. Perou

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)165-178
Number of pages14
JournalBreast Cancer Research and Treatment
Volume188
Issue number1
DOIs
Publication statusPublished - 2021 Jul

Bibliographical note

Funding Information:
This work was supported by funds from the Basic Science Research Program through the NRF (NRF-2019R1C1C1002830), a Grant (HI14C3396) by Ministry of Health & Welfare, Republic of Korea, and by the Susan G. Komen Foundation (CMP) and the Breast Cancer Research Foundation (CMP).

Funding Information:
This work was supported by funds from the Breast Cancer Research Foundation, the Basic Science Research Program through the NRF (NRF-2019R1C1C1002830), a grant (HI14C3396) by Ministry of Health & Welfare, Republic of Korea, and by the Susan G. Komen Foundation.

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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