Abstract 5006: Correlation between PD-L1 expression and tumor clinicopathologic characteristics in early stage breast cancer
Authors: Assad Hadeel , Cattoni Juan , Arekapudi Subramanyeswara , Jackson Nancy , Cattoni Hugo Macchi , Motahari Sherri , Govil Hema , Drelichman Anibal 
Published: July 2017

Background: Upregulation of Programmed Death-Ligand 1 (PD-L1) in tumor cells results in the deactivation of cytotoxic T cells in the tumor microenvironment and development of tolerance to the malignant cells. We aimed to investigate the role of PD-L1 expression in early stage breast cancer and its correlation with tumor characteristics as well as assess the relationship between PD-L1 membrane protein and gene expression.

Methods: For this single center, retrospective study, women (age &gt;18 years) with early stage breast cancer diagnosed between January 2005 and December 2005 were enrolled. Key inclusion criteria for enrollment were pathologic diagnosis of DCIS or invasive ductal/lobular carcinoma, stage 0-2, with local resection done in 2005. Patients had to have adequate formalin-fixed paraffin-embedded tumor specimens for PD-L1 testing. We hypothesized that higher levels of PD-L1 expression correlates with more aggressive disease and worse prognosis. We used histopathological analysis, medical chart review, and PD-L1 expression via immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) for data analysis. Chi Square and one way ANOVA analyses were used to compare clinical and pathological characteristics of patients with high and low PD-L1 expression.

Results In 2005, 368 women were diagnosed with breast cancer at Providence-Providence Park Hospital of which 31 pathological specimens were obtained for exploratory analysis. PD-L1 protein expression was determined to be positive if more than 1% of the tumor cells showed partial or complete membrane staining for PD-L1 by IHC. All patients with DCIS (n=7) were negative for PDL-1 expression although 3 showed gene expression by PCR. After excluding the DCIS specimens, 17% (4/24) of early stage breast cancer was found to express PD-L1 protein. Seven of 24 specimens (excluding DCIS) were positive for PD-L1 RNA by RT-PCR. There was no relationship between PD-L1 protein and mRNA expression (p=0.552). 75% of the PD-L1 positive specimens by IHC were also ER positive although this was not statistically significant (p=0.312). There was a trend toward larger tumors for those expressing PD-L1 on the cell surface (mean size of 2.7 cm vs 1.7 cm, p= 0.07). All the PD-L1 positive specimens had increased lymphocyte infiltration, although no statistical significance was observed. At 10 years from initial diagnosis, all-cause mortality rate was 29% (7/24). The rate of death in PD-L1 positive patients was 2/4 (50%) compared to 5/20 (25%) in PD-L1 negative group.

Conclusion: Expression of PD-L1 in early stage breast cancer could be an important indicator for more aggressive disease and supports investigating checkpoint inhibitors in this population. Further investigation is needed to determine its applicability in clinical decisions and effects on treatment.

Citation Format: Hadeel Assad, Juan Cattoni, Subramanyeswara Arekapudi, Nancy Jackson, Hugo Macchi Cattoni, Sherri Motahari, Hema Govil, Anibal Drelichman. Correlation between PD-L1 expression and tumor clinicopathologic characteristics in early stage breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5006. doi:10.1158/1538-7445.AM2017-5006