Expression of PD-L1 using SP142 CDx in triple negative breast cancer

Al-Jussani, Ghada N.; Dabbagh, Tamara Z.; Al-Rimawi, Dalia; Sughayer, Maher A.

doi:10.1016/j.anndiagpath.2021.151703

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…These findings point to a potential beneficial role for T-regs and infiltration of GITR expressing TILs in modulating immune activity for patient survival. Similarly, our observation that tumour cell PD-L1 expression in TNBC is positively associated with improved OS is consistent with published findings ( 15 , 40 ). Furthermore, PD-L1 positive disease displayed improved OS in response to anti-PD-L1 immunotherapy in phase III IMpassion130 trial ( 41 ), and has subsequently shown improved outcome in response to combination therapies ( 18 ).…”

Section: Discussionsupporting

confidence: 93%

Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

et al. 2022

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Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that has few effective treatment options due to its lack of targetable hormone receptors. Whilst the degree of tumour infiltrating lymphocytes (TILs) has been shown to associate with therapy response and prognosis, deeper characterization of the molecular diversity that may mediate chemotherapeutic response is lacking. Here we applied targeted proteomic analysis of both chemotherapy sensitive and resistant TNBC tissue samples by the Nanostring GeoMx Digital Spatial Platform (DSP). By quantifying 68 targets in the tumour and tumour microenvironment (TME) compartments and performing differential expression analysis between responsive and non-responsive tumours, we show that increased ER-alpha expression and decreased 4-1BB and MART1 within the stromal compartments is associated with adjuvant chemotherapy response. Similarly, higher expression of GZMA, STING and fibronectin and lower levels of CD80 were associated with response within tumour compartments. Univariate overall-survival (OS) analysis of stromal proteins supported these findings, with ER-alpha expression (HR=0.19, p=0.0012) associated with better OS while MART1 expression (HR=2.3, p=0.035) was indicative of poorer OS. Proteins within tumour compartments consistent with longer OS included PD-L1 (HR=0.53, p=0.023), FOXP3 (HR=0.5, p=0.026), GITR (HR=0.51, p=0.036), SMA (HR=0.59, p=0.043), while EPCAM (HR=1.7, p=0.045), and CD95 (HR=4.9, p=0.046) expression were associated with shorter OS. Our data provides early insights into the levels of these markers in the TNBC tumour microenvironment, and their association with chemotherapeutic response and patient survival.

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Section: Discussionsupporting

confidence: 93%

Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

et al. 2022

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“… 29 In TNBC, PD-L1-IC expression by SP142 was reported from 28 to 56% while a range of 5-37% was reported for its TC expression. 12 , 13 , 23 , 30 In our cohort, the PD-L1 expression rates on TNBC IC and TC were 57.5% and 11.6%, respectively, similar to those reported previously. These figures were close to the upper boundary of the reported range, higher than that in the IMpassion130 trial.…”

Section: Discussionsupporting

confidence: 90%

Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes

Tsang

Shao

et al. 2022

The Oncologist

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Background PD-L1 has been used as a biomarker to select patients for treatment of PD-1/PD-L1 inhibitors. Materials and Methods In this study, we assessed the clinicopathological features of breast cancers that are associated with PD-L1 expression, as well as its relationship with other immune components and its prognostic significance. Results Totally 1752 cases were included in this cohort. PD-L1 expression in tumor-infiltrating immune cells (PD-L1-IC) expression and in tumor cells (PD-L1-TC) expression were identified in 34.2% and 10.1% of cases, respectively, and they showed a positive correlation with higher tumor grade, morphological apocrine features, presence of necrosis, and higher stromal tumor-infiltrating lymphocytes (sTIL). PD-L1-IC and PD-L1-TC expression correlated positively with each other, and both of them were negatively associated with estrogen receptor and progesterone receptor and positively associated with Ki67, HER2, EGFR, p63, and p-cadherin. In survival analysis, PD-L1-IC expression was associated with better disease-free survival (DFS) and breast cancer-specific survival (BCSS) in HER2-overexpressed (HER2-OE) cancers and high–grade luminal B cancers. In triple–negative breast cancers (TNBC) and HER2–OE cancers, compared with sTIL low PD-L1-IC negative cases, sTIL high cases showed significantly better DFS independent of PD-L1-IC status. sTIL low PD-L1-IC positive cases also demonstrated a better DFS in HER2–OE cancers. In high–grade luminal B cancers, sTIL high PD-L1-IC positive cases showed the best BCSS. Conclusion The data suggested that the combining analysis of sTIL and PD-L1-IC expression refined the prognostication of breast cancer subtypes. Cases with high TIL and PD-LI-IC expression appear to be more immune active.

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“…The proportion of pCR, baseline neutrophil, lymphocyte count and platelet count was recorded. The median cut-off value for high NLR was taken as 3.0 and for platelet lymphocyte ratio (PLR) it was 185 based on a published meta-analysis [ 14 , 15 ]. The pCR was defined either by the complete absence from both breast tissue and nodes or only the presence of in situ components [ 16 ].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, tumours with a high degree of infiltrating lymphocytes (TILs) have a higher probability of achieving a pCR [ 12 ]. Immune checkpoint inhibitors (ICIs) such as atezolizumab have shown better outcomes when combined with chemotherapy in metastatic TNBC, more so in the programmed death ligand 1 (PDL1)-positive subset [ 13 , 14 ]. Pembrolizumab, another ICI, has also been studied in the neoadjuvant setting and has showed significantly higher pCR [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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

Ghosh

Chatterjee

Ganguly

et al. 2021

ecancer

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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.

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Expression of PD-L1 using SP142 CDx in triple negative breast cancer

Cited by 9 publications

References 22 publications

Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

Spatial Profiling Identifies Prognostic Features of Response to Adjuvant Therapy in Triple Negative Breast Cancer (TNBC)

Combining Analysis of Tumor-infiltrating Lymphocytes (TIL) and PD-L1 Refined the Prognostication of Breast Cancer Subtypes

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

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