Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with high recurrence rates, a high incidence of distant metastases and poor overall survival. The aim of this study was to investigate the role of PD-L1, EGFR and AR expression in TNBC promotion and progression. To that end, we analyzed the immunohistochemical expression of these genes in 125 TNBC patients and their relation to clinicopathological parameters and survival. An elevated expression of PD-L1 was significantly correlated with higher tumor and nuclear grade, while a low expression was correlated with loco-regional recurrence without any influence on survival. Contrary to this, the expression of AR showed a positive impact on the DFI and a negative association with tumor grade. Furthermore, PD-L1 and AR demonstrated simultaneous expression, and further co-expression analysis revealed that a positive expression of PD-L1/AR notably correlates with tumor and nuclear grade and has a significant impact on a longer DFI and OS, while a negative PD-L1/AR expression is significantly associated with metastases. Therefore, our results suggest that positive PD-L1/AR expression is beneficial for TNBC patients. In addition, an elevated expression of EGFR contributes to metastases and a worse DFI and OS. In conclusion, we think that low PD-L1/low AR/high EGFR expression followed by high Ki67 expression constitutes a ‘high risk’ profile of TNBC.

Background/Objectives: Triple-negative breast cancer (TNBC) is characterized by the absence of the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2. As there are no specific targeted therapies, TNBC patients often face an aggressive clinical course. The expression of the androgen receptor (AR) has been found in up to 30% of TNBC cases, but the association between the AR status and survival rates in TNBC remains controversial. The aim of this study was to explore the association of AR expression with the disease outcome in patients with early TNBC within a 5-year follow-up. Methods: AR expression was determined by immunohistochemistry in a cohort of 124 early-TNBC patients treated at the Institute for Oncology and Radiology of Serbia. The cut-off value used for the positive AR status was >10% tumor cells. The association of the AR status with clinicopathological factors (age, stage, tumor diameter, lymph node invasion, metastatic spread, Ki-67 score, EGFR score, and cytokeratin 5/6 score) and the disease outcome (disease-free survival—DFS—and overall survival—OS) was investigated. Results: Our analysis showed that the AR-positive status was associated with a significantly lower Ki-67 score compared to the AR-negative samples. A univariate analysis indicated that the age, tumor size, nodal status, and EGFR score significantly influenced both 5-year DFS and OS. Multivariate Cox analysis suggested that a smaller tumor size, lower nodal status, and AR expression were independent predictors of longer survival rates in TNBC patients. Conclusions: The results of this study suggest that the positive AR status may be a favorable prognostic factor in TNBC patients within the first five years after surgery.

Breast cancer is the most frequent and lethal type of cancer that affects women worldwide. Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, having high rate of recurrence, metastasis, and mortality, with very limited options for treatment, and a tendency to develop resistance to conventional therapy. These circumstances mean that it is necessary to develop effective therapies for TNBC patients which would circumvent resistance mechanisms. The PAM and Wnt signaling pathways are among those responsible for therapy resistance in TNBC, as they also have major roles in different cellular processes such as metabolism, proliferation, metastasis, stemness, and survival. We analysed the expression of GSK3β and S6K1 as interacting components of the two pathways in order to examine the relation between them and determine whether they could be used as predictive markers in TNBC. The expression of mRNA was examined with real-time PCR and protein expression with immunohistochemistry. Our results showed that protein expression is in line with mRNA expression. We found a positive correlation between the mRNA expressions of GSK3β and S6K1, showing their coordinated transcription. We also showed that their simultaneous low expression is unfavorable for TNBC patients and could possibly be used as a predictive marker.