scholarly journals Prognostic Significance of Tumor–infiltrating Lymphocytes and Androgen Receptors in Patients with Early Triple-negative Breast Cancer

Author(s):  
Ana Tečić Vuger ◽  
Robert Šeparović ◽  
Sanda Šitić ◽  
Ljubica Vazdar ◽  
Mirjana Pavlović ◽  
...  

Abstract Aims This study aimed to investigate the association between tumor-infiltrating lymphocytes (TIL) and androgen receptors (AR) and to assess their impact on early triple-negative breast cancer (TNBC) prognosis. Previous studies analyzed only stromal TIL (sTIL) and intratumoral (ITIL), while this study includes an additional spatial analysis for TIL in central tumor (CT) and invasive margin (IM) compartments and correlation with AR expression and overall survival (OS). Methods A retrospective cohort study encompassing 152 early TNBC tissue samples from patients treated at a tertiary oncologic center between 2009 and 2012. TIL and AR were assessed using formalin-fixed paraffin-embedded samples, using hematoxylin-eosin staining and immunohistochemistry. AR-positive tumors were considered those with ≥ 1% nuclear-stained cells. Results High TIL indicators were found to be positive prognostic factors. Although AR was not an independent prognostic factor, its interactions with sTIL and ITIL at IM impacted OS. Positive AR along with high sTIL and ITIL in IM were associated with favorable OS (HR for sTIL 0.22; 95%CI 0.05–0.97; p = 0.045 and HR for ITIL 0.10; 95%CI 0.01–0.78; p = 0.028). Conclusion Spatial morphological analysis of TIL reveals an additional prognostic value when combined with AR status, and shows a clinically significant impact on OS in early TNBC.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12571-e12571
Author(s):  
Ana Tecic Vuger ◽  
Robert Separovic ◽  
Ljubica Vazdar ◽  
Mirjana Pavlovic ◽  
Sanda Sitic ◽  
...  

e12571 Background: Little is known about correlation of tumor infiltrating lymphocytes (TIL) and androgen receptors (AR) and their joint effect on early triple-negative breast cancer (TNBC) prognosis. Analyzes to date evaluated mostly stromal TIL (sTIL) and intratumoral (iTIL), but not separately in central tumor (CT) and invasive margin (IM). Methods: We retrospectively analyzed consecutive sample of 152 early TNBC patients treated at our institution 2009-2012. TIL and AR were assessed using standard FFPE samples, TIL according to International Working Group for Evaluation of TIL recommendation, sTIL and iTIL in CT and IM, and AR by immunohistochemistry. Results: Median age was 58, 84% NOS, median T 2.2cm, 41% N+, 22%, 59% and 19% in stage I, II and III, respectively. Radical mastectomy was performed in 39%, adjuvant chemotherapy in 88% and radiotherapy in 74% of patients. Positive AR defined as ≥1% nuclear-stained cells, were expressed in 31%, and AR≥10% in 26% of patients. Median TIL content was: sTIL 19%, iTIL 5%, TIL in CT 5%, at IM 18%, sTIL in CT (CTs) 5%, iTIL in CT (CTi) 1%, sTIL at IM (IMs) 30%, and iTIL at IM (IMi) 5%. Prevalence of intermediate or high TIL content, defined as ≥10% was: CTs in 48%, CTi in 23%, IMs in 86%, and IMi in 47% of cases. In bivariable analysis all TIL indicators were significantly associated with longer OS, while AR was not. After adjustment for potential confounders using Cox proportional hazard regression, significant predictors of OS were sTIL (p0.007), IM TIL (p0.002), IMs (p0.001), and IMi (p0.030). In all cases higher TIL content was associated with longer OS. Although AR was not significant predictor of OS, it's interactions with TIL IMs and IMi was. There was no significant difference in OS between patients with high IMs and low IMs and AR0, but those with high IMs and AR≥1 had HR0.22 (p0.045) for death compared to patients with low IMs and AR0. Also, no difference for high IMi and low IMi and AR0, but patients with high IMi and AR≥1 had HR0.10 (p0.028) for death compared to patients with low IMi and AR0. Conclusions: Section analysis reveals frequent intermediate to high density and statistically significant prognostic impact of TIL on IM. That directs question towards role of different tumor compartments. Furthermore, combination of high expression of IMs and IMi with AR≥1 appears to be associated with longer OS than in patients with high IMs and IMi but with AR0. The correlations between AR and all TIL studied are extremely small, indicating their independence, but if so, their interaction in impact on OS is particularly interesting.


Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.


2015 ◽  
Vol 7 (4) ◽  
pp. 232-241
Author(s):  
Koo Si-Lin ◽  
Loh Kiley ◽  
Sulastri Kamis ◽  
Jabed Iqbal ◽  
Rebecca Dent ◽  
...  

2021 ◽  
Vol 49 (1) ◽  
pp. 20-28
Author(s):  
Ana Tečić-Vuger ◽  
◽  
Robert Šeparović ◽  
Ljubica Vazdar ◽  
Mirjana Pavlović ◽  
...  

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