Abstract 25P
Background
Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death worldwide. This heterogeneous disease has been historically considered a non-immunogenic type of cancer. However, recent advances in immunotherapy have increased the interest in knowing the role of the immune checkpoints (IC) in this neoplasia. Thus, we analyzed the mRNA expression of CTLA-4, PDCD1 (PD1), CD274 (PD-L1), and PDCD1LG2 (PD-L2) and evaluated the correlation with clinicopathological factors and patient outcome.
Methods
We included 275 non-consecutive BC patients (18.2% Luminal A, 18.2% Luminal B/HER2-, 21.1% Luminal B/HER2+, 20.7% HER2-enriched and 21.8% Triple-Negative/Basal-like). The mRNA expression was analyzed by qRT-PCR using TaqMan® primers and probes. PUM1 and β-actin were used as reference genes, and healthy breast tissue served as a calibrator. The 2-ΔΔCT calculated relative changes in gene expression. Molecular results were correlated with clinicopathological factors (age, tumor size and grade, vascular invasion, necrosis, immunophenotype, tumor-infiltrating lymphocytes -TILs-, lymph node status, Ki67), and prognosis. Significant differences were calculated with χ2 and log-rank test.
Results
Overexpression of at least one IC was found in 95.2% of samples. CTLA-4 and PDCD1 expression were associated with Triple-Negative/Basal-like and Luminal B/HER2+ tumors, respectively (both p=0.046), whereas CD274 and PDCD1LG2 showed no correlation with BC immunophenotypes. High CTLA-4, PDCD1, CD274, and PDCD1LG2 expression were associated with a middle/high proliferation rate (all p≤0.039) and high TILs density (all p≤0.011). In addition, CTLA-4 overexpression correlated with better disease-free survival -DFS- (p=0.037), specifically among HER2-enriched subtype (DFS p=0.033, and overall survival p=0.011).
Conclusions
Our data support that CTLA-4, PDCD1, CD274, and PDCD1LG2 are potential biomarkers of BC aggressiveness. Paradoxically, CTLA-4 stratified a subgroup of HER2-enriched patients with a better outcome. Supported by Grants ISABIAL (NR-180202, UGP-18-231, UGP-19-291, UGP-20-090); Biobank HGUDB (21-154) and HUB-ICO-IDIBELL (PT17/0015/0024).
Legal entity responsible for the study
The authors.
Funding
Supported by Grants ISABIAL (NR-180202, UGP-18-231, UGP-19-291, UGP-20-090); Biobank HGUDB (21-154) and HUB-ICO-IDIBELL (PT17/0015/0024).
Disclosure
All authors have declared no conflicts of interest.