Programmed Death Ligand 1 (PD-L1) Tumor Expression Is Associated with a Better Prognosis and Diabetic Disease in Triple Negative Breast Cancer Patients.
PD-L1 expression was detected in 72% of the cases, and it expressed in a higher percentage and higher intensity in TILs than TCs in TNBC (p = 0.006 and 0.0005, respectively).
A trend toward a higher ORR was seen in patients with PD-L1+ versus PD-L1- tumor-associated immune cells in the overall population (16.7% vs. 1.6%) and in the TNBC subgroup (22.2% vs. 2.6%).
Among the breast cancer subtypes, evaluation of ICB has been of greatest interest in triple-negative breast cancer (TNBC) due to its immunogenicity, as evidenced by the presence of tumor-infiltrating lymphocytes and elevated PD-L1 expression relative to other subtypes.
Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup.
Based on analysis of breast cancer tissue samples deposited in The Cancer Genome Atlas (TCGA), we found a positive correlation between PD-L1 and focal adhesion kinase (FAK) mRNA expression in PD-L1-positive (PD-L1<sup>+</sup>) TNBC, suggesting a functional association of FAK and immune checkpoints.
Based on IMpassion130 clinical trial (NCT02425891), the Food and Drug Administration (FDA) has recently granted an accelerated approval for atezolizumab (TECENTRIQ®), a monoclonal antibody drug targeting PD-L1, plus chemotherapy (Abraxane; nab®-Paclitaxel) for the treatment of adults with PD-L1-positive, unresectable, locally advanced or metastatic TNBC.
Combining the PD-L1 inhibitor atezolizumab with standard chemotherapy improves overall survival among patients with metastatic triple-negative breast cancer relative to chemotherapy alone.
Expert opinion: Atezolizumab, a novel immune checkpoint inhibitors targeting PD-L1, is an effective and well-tolerated treatment option for metastatic TNBC.
For patients with PD-L1 immune cell-positive metastatic triple-negative breast cancer, atezolizumab plus nab-paclitaxel is an important therapeutic option in a disease with high unmet need.
Furthermore, we found that targeting both MHC-I and II restricted tumor epitopes was necessary to decrease the growth of the poorly immunogenic TNBC model 4T1 and that combination with PD-L1 blockade increased the number of responders to checkpoint inhibition.
Higher PD-L1 expression in tumor cell was related to larger tumor size, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor type-2 positivity, and triple-negative breast cancer.
However in the multivariate analysis only PD-L1 expression on tumor cells remained significantly associated with pCR (OR = 1,13; 95% CI 1,01-1,27), suggesting that the expression of this biomarker could be associated with a subpopulation of TNBC more likely to respond to chemotherapy.
Immunohistochemistry and RNAscope were used to semi quantitively evaluate PD1/PDL1 protein and mRNA expression in 195 TNBC cases on tissue microarrays.