PDL1 expression and its correlation with outcomes in non-metastatic triple-negative breast cancer (TNBC)

Abstract

Purpose: Triple-negative breast cancer (TNBC) has a poor outcome compared to other subtypes, even in those with early disease. Immune checkpoint inhibitors (ICIs) have been approved in metastatic diseases and are being tested as a neoadjuvant strategy also. The response to ICIs is largely determined by the programmed death ligand 1 (PDL1) score, which also acts as a prognostic marker for outcomes. Here, we report the proportion of PDL1 expression in non-metastatic TNBC and its correlation with response to chemotherapy and outcomes. Methods:We included all patients who had non-metastatic TNBC treated with neoadjuvant chemotherapy, followed by surgery with/without adjuvant radiotherapy between September 2011 and November 2017. PDL1 testing was carried out on pre-treatment tumour cells with immunohistochemistry (Ventana SP142) and was correlated with pathological response, relapse-free survival (RFS) and overall survival (OS). PDL1 staining was interpreted as negative or positive (more than 1% staining).Results: A total of 107 patients were included for analysis with a median age of 47 years (28-65 yrs). The PDL1 expression of more than 1% was seen in 31 (28.97%) patients. After a median follow-up of 55 months (range: 4-93 months), median RFS and OS were not reached. PDL1 expression did not affect the achievement of pathological complete response (pCR). However, PDL1 expression improved OS (p = 0.016) and trend towards RFS (p = 0.05). Patients who achieved pCR had better RFS and OC compared to those who did not. Conclusion:Our study shows PDL1 expression in 29% of the cases. PDL1 expression leads to better RFS and OS. Also, pCR improves survival.

Programmed Death-Ligand 1 (PD-L1) as Immunotherapy Biomarker in Breast Cancer

“…In early TNBC, previous studies have found that PD-L1 is overexpressed in around 45 to 55% of the tumor cells, whereas, in the advanced disease, the expression of PD-L1 is about 35% [ 61 , 73 ].…”

“…Some studies have examined the expression of PD-L1 and PD-L2 in patients with early TNBC, showing that about 55% and 50%, respectively, were positive [ 16 ]. Unexpectedly, despite a higher relapse rate in PD-L1-positive patients, their OS was better than in PD-L1-negative subgroups [ 57 , 73 ], a fact that could be linked to a stronger underlying antitumor immune response secondary to treatment [ 55 ]. Moreover, PD-L1 expression in TNBC has been positively associated with the expression of other immune system regulators, such as indoleamine 2,3-dioxygenase 1 (IDO1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in addition to BRCA1 gene mutations [ 17 ].…”

The PD-L1 Expression Among Triple-Negative Breast Cancer Patients in Universitas Sumatera Utara Teaching Hospital, Indonesia

“…Cut-off value of PD-L1 as measured by different assays e.g., SP142, SP263, and 22C3 as proved by Lee et al, also proved to be significant in determining PD-L1 expression rate in its TNBC populations; with the value of 5% in tumor cell component analysis showed the positivity rate of 6-43% in those assays. Ghosh et al, in 2021 also had reported that the rate of PD-L1 expression among non-metastatic TNBC was 31.3% ( 13 – 15 ). Therefore, we believe our findings in Indonesia is concordant and similar to the global study specifically in Asian region since both latter studies were conducted on South Korea, China, and India respectively.…”

Clinicopathological and Prognostic Significance of Programmed Death Ligand-1 SP142 Expression in 132 Patients With Triple-negative Breast Cancer

“…In published data using E1L3N antibody in TNBC, the relationship between positive PD-L1 expression and patient outcome varied from better (39)(40)(41) to worse (42,43) or insignificant (44,45). Similarly, some previous studies regarding the SP142 antibody on TNBC revealed an association between positive PD-L1 expression and better outcomes (21,26,46), whereas a recent study on 223 patients with TNBC showed that PD-L1 SP142 expression in ICs was independently prognostic of worse overall survival (47). Similarly, the cutoff scores for positive or high PD-L1 expression vary among studies.…”