PD-1 protein and gene expression in early breast cancer: Prognostic implications.

Authors

null

Ioannis Zerdes

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden

Ioannis Zerdes , Alexios Matikas , John Lövrot , Emmanouil G. Sifakis , François Richard , Christos Sotiriou , George Z. Rassidakis , Jonas C. S. Bergh , Antonios Valachis , Theodoros Foukakis

Organizations

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden, Karolinska Institutet and University Hospital, Stockholm, Sweden, Department of Oncology, KU Leuven, Leuven, Belgium, Institut Jules Bordet, Brussels, Belgium, Örebro University Hospital, Örebro, Sweden

Research Funding

Other
Swedish Cancer Society, Cancer Society in Stockholm, Swedish Breast Cancer Association

Background: We have previously shown the prognostic value of PD-L1 protein and gene expression in early breast cancer (BC), however, the prognostic role of PD-1 expression remains unclear. Methods: The prognostic value of PD-1 in early BC was investigated using three different approaches: i) evaluation of PD-1 at the protein (IHC, immunohistochemistry in tissue microarrays) and mRNA levels in a retrospective patient cohort of 586 patients treated for early BC in Stockholm, Sweden between 1997-2005, ii) systematic review and trial-level meta-analysis of studies published in Medline, Embase, Cochrane Library and Web of Science Core Collection libraries on the prognostic value of PD-1 IHC expression, and iii) pooled analysis of transcriptomic data from 39 publicly available datasets for the prognostic capacity of PD-1 gene expression. Univariate and multivariable Cox regression models were used. Results: In the retrospective study cohort, PD-1 protein was significantly associated with biologically high-risk characteristics. PD-1 protein, but not gene expression, was correlated with improved overall survival (OS) (adjusted HR = 0.73, 95% CI 0.55 – 0.96, p = 0.023 and adjusted HR = 0.88, 95% CI 0.68 – 1.13, p = 0.307, respectively). In the trial-level meta-analysis, 4736 entries were initially identified and 15 studies, including our original cohort, fulfilled the predefined eligibility criteria. PD-1 IHC expression was not prognostic in unselected patients. However, a significant correlation to improved disease-free survival was seen within the triple-negative subtype (pooled multivariate HR = 0.57, 95% CI 0.29 – 0.90, p = 0.02). In the pooled gene expression analysis, PD-1 gene expression was associated with improved OS in the entire population (adjusted HR = 0.89, 95% CI 0.80 – 0.99, p = 0.025) and in basal-like (adjusted HR = 0.77, 95% CI 0.63 – 0.95, p = 0.014) tumors. Conclusions: PD-1 expression at the RNA and protein levels represent promising prognostic factors, especially in the triple-negative and basal-like subtypes. Standardization and further validation are needed prior to clinical implementation.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Breast Cancer—Local/Regional/Adjuvant

Track

Breast Cancer

Sub Track

Adjuvant Therapy

Citation

J Clin Oncol 38: 2020 (suppl; abstr 545)

DOI

10.1200/JCO.2020.38.15_suppl.545

Abstract #

545

Poster Bd #

37

Abstract Disclosures

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