Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival. (2nd December 2018)

• Record Type: Journal Article
• Authors: Sobral-Leite, Marcelo; Van de Vijver, Koen; Michaut, Magali; van der Linden, Rianne; Hooijer, Gerrit K.J.; Horlings, Hugo M.; Severson, Tesa M.; Mulligan, Anna Marie; Weerasooriya, Nayana; Sanders, Joyce; Glas, Annuska M; Wehkamp, Diederik; Mittempergher, Lorenza; Kersten, Kelly; Cimino-Mathews, Ashley; Peters, Dennis; Hooijberg, Erik; Broeks, Annegien; van de Vijver, Marc J.; Bernards, Rene; Andrulis, Irene L.; Kok, Marleen; de Visser, Karin E.; Schmidt, Marjanka K.
• Is Part Of: Oncoimmunology. Volume 7:Number 12(2018)
• Publication Date: 2018-12-02
• Subjects: Breast cancer -- PD-L1 -- TILs -- mutations -- BRCA1-like; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1509820
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: To better understand the expression pattern of programmed death-ligand 1 (PD-L1) expression in different breast cancer types, we characterized PD-L1 expression in tumor and tumor-infiltrating immune cells, in relation to mutation rate, BRCA1 -like status and survival. We analyzed 410 primary treatment-naive breast tumors comprising 162 estrogen receptor-positive (ER+) and HER2−, 101 HER2+ and 147 triple-negative (TN) cancers. Pathologists quantified tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in tumor cells and TILs using whole slides and tissue microarray. Mutation rate was assessed by DNA sequencing, BRCA1 -like status using multiplex ligation-dependent probe amplification, and immune landscape by multiplex image analyses of CD4, CD68, CD8, FOXP3, cytokeratin, and PD-L1. Half of PD-L1 scores evaluated by tissue microarray were false negatives compared to whole slide evaluations. We observed at least 1% of PD-L1-positive (PD-L1+) cells in 53.1% of ER+HER2−, 73.3% of HER2+, and 84.4% of TN tumors. PD-L1 expression was higher in ductal compared to lobular carcinomas, also within ER+HER2− tumors (p = 0.04). High PD-L1+ TILs score (> 50%) was independently associated with better outcome in TN tumors (HR = 0.27; 95%CI = 0.10–0.69). Within TN tumors, PD-L1 and TIL scores showed a modest but significant positive association with the number of silent mutations, but no association with BRCA1 -like status. Multiplex image analyses indicated that PD-L1 is expressed on multiple immune cells (CD68+ macrophages, CD4+, FOXP3+, and CD8+ T cells) in the breast tumor microenvironment, independent of the PD-L1 status of the tumor cells. We found no evidence that levels of PD-L1+ TILs in TN breast cancer are driven by high mutation rate or BRCA1 -like status.