Abstract
Purpose
The interaction of the programmed cell death 1 (PD-1) receptor on tumor-infiltrating lymphocytes with programmed death ligand 1 (PD-L1) on tumor cells downregulates anti-tumor immunity. This study evaluated associations between PD-1 and PD-L1 expression in primary breast cancer, clinical characteristics, and patient outcomes.
Methods
Microarray data from the Investigation of Serial Studies to predict your therapeutic response with imaging and molecular analysis (I-SPY 1) study (n = 149) was used to evaluate PD-1 and PD-L1 expression. Associations with clinical features and chemotherapy response were determined using Kruskal–Wallis and Wilcoxon rank sum tests, respectively. Recurrence-free survival (RFS) associations were determined with the Cox proportional hazard model. Associations of PD-1 and PD-L1 and selected genes associated with breast cancer, as well as a predictor of olaparib response (PARPi-7), were determined in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817), using Pearson correlations.
Results
In I-SPY 1, PD-1 expression was higher in triple-negative breast cancer (TNBC) and HER2 + breast cancer (p = 0.003), and grade 2/3 tumors (p = 0.043), and was associated with pathologic complete response (p = 0.006). PD-L1 expression in the lowest quintile was associated with worse RFS, even after subtype adjustment (HR 2.33, p = 0.01). PD-1 and PD-L1 gene expression correlated with the expression of immune-related genes and PARPi-7.
Conclusions
PD-1 expression is higher in breast cancers with aggressive features such as TNBC. Low PD-L1 expression may be an adverse prognostic factor. PD-1 and PD-L1 gene expression correlates with the expression of immune-related and DNA damage repair genes.
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Data availability
The datasets used for this study (I-SPY 1, METABRIC, and TCGA) are publically available. I-SPY 1 datasets were accessed in NCBI Gene Expression Omnibus (GEO) (https://identifiers.org/geo:GSE22226), METABRIC data in European Genome-phenome Archive (EGA) (https://identifiers.org/ega.dataset:EGAD00010000210 and https://identifiers.org/ega.dataset:EGAD00010000211), and TCGA data in cBioPortal for CancerGenomics (https://identifiers.org/cbioportal:brca_tcga_pub2015).
Abbreviations
- PD-1:
-
Programmed cell death 1
- PD-L1:
-
Programmed death ligand 1
- TNBC:
-
Triple-negative breast cancer
- HR positive disease:
-
Hormone receptor positive disease
- pCR:
-
Pathologic complete response
- RFS:
-
Recurrence-free survival
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Acknowledgements
The authors would like to acknowledge the I-SPY 1 study participants and staff. The authors would like to acknowledge the Conquer Cancer Foundation of the American Society of Clinical Oncology for providing Dr. Vidula with a Merit Award (2015) for presenting a portion of this work at the 2015 Annual Meeting. They would also like to acknowledge ABC3-Advanced Breast Cancer Third International Consensus Conference for a travel award for Dr. Vidula to present a portion of this work at this conference. While this study was not funded, the I-SPY 1 clinical trial (CALGB 150007/150012; ACRIN 6657) was funded through the Alliance Grant U10CA180821.
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Vidula, N., Yau, C. & Rugo, H.S. Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) gene expression in primary breast cancer. Breast Cancer Res Treat 187, 387–395 (2021). https://doi.org/10.1007/s10549-021-06234-3
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DOI: https://doi.org/10.1007/s10549-021-06234-3