175 Metastatic triple negative breast cancer has distinct tumor immune landscape Article Swipe
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1136/jitc-2023-sitc2023.0175
· OA: W4388042703
<h3>Background</h3> Triple negative breast cancer (TNBC) is considered the most immunogenic breast cancer subtype due to higher levels of tumor infiltrating immune cells (TILS), elevated tumor mutational burden and PD-L1 expression, providing a rationale for immunotherapy. Here we aimed to investigate the differences in the immune microenvironment in TNBC vs. non-TNBC for primary and metastatic sites and their impact on survival. <h3>Methods</h3> Comprehensive immune profiling, including PD-L1 IHC and the expression of 395 immune genes, was performed on 147 real-world FFPE breast cancer samples (32 primary, 115 metastatic). 37 samples were, by definition, triple negative for ER, PR, and HER2 overexpression. PD-L1 (CPS positive ≥1 and CPS positive ≥10) was determined using immunohistochemistry (SP142 and 22C3). mRNA expression signatures of tumor inflammation (TIGS, weak/moderate/strong) and cell proliferation (CP, poor/moderate/high) were determined by RNA-sequencing. Statistical comparisons of biomarkers between group were calculated using the Wilcoxon Rank-Sum test (p<0.05 for significance) and survival differences were quantified by Cox proportional hazards analysis. <h3>Results</h3> Comparing TNBC and non-TNBC cases, TNBC cases were observed to have significantly higher TIGS [p=0.014] and PD-L1 expression [p=4.4×10<sup>-7</sup>]. Additionally, TNBC cases trended toward exhibiting greater cell proliferation [p=0.069]. These differences were found to be driven primarily by metastatic tumors, for which TNBC tumors showed significantly higher TIGS [p=0.015], cell proliferation [p=0.021], and PD-L1 expression [p=2.9×10<sup>-7</sup>] than non-TNBC tumors, while none of these significant associations were observed among primary tumors. For the entire cohort, PD-L1 positivity was significantly associated with worse survival for positivity thresholds of both 1% [HR=1.70, p=0.011] and 10% CPS [HR=1.54, p=0.042]. These trends were also found to be driven by metastatic tumors [1% threshold: HR=1.76, p=0.016; 10% threshold: HR=1.66, p=0.033]. Additionally, high cell proliferation status was significantly associated with worse survival [HR=1.83, p=0.03] regardless of TNBC status. <h3>Conclusions</h3> Our comprehensive biomarker analyses showed that metastatic TNBC has a more inflamed tumor microenvironment and higher checkpoint target expression compared to non-TNBCs. Interestingly, we observed that although metastatic TNBC has a higher median PD-L1 CPS, tumors with lower PD-L1 expression had better overall survival. Further analysis of immune expression by site-specific metastases and correlation with immunotherapy outcomes is warranted to guide clinicians in selection of the ideal metastatic site to biopsy for therapeutic decision making. However, in a collective TNBC context, these data support the use of immunotherapy in metastatic TNBC. <h3>Ethics Approval</h3> Ethics approval for this study was obtained from Roswell Park Comprehensive Cancer Center Institutional Review Board (Study# BDR 162622) and determined to be non-human subject research.
