Tumor-Infiltrating Lymphocyte Volume Is a Better Predictor of Disease-Free Survival Than Stromal Tumor-Infiltrating Lymphocytes in Invasive Breast Carcinoma

2019 ◽  
Vol 152 (5) ◽  
pp. 656-665 ◽  
Author(s):  
Elmira Vaziri Fard ◽  
Yasir Ali ◽  
Xiaohong I Wang ◽  
Karan Saluja ◽  
Michael H Covinsky ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Stroma ◽  
Invasive Breast Carcinoma ◽  
Free Survival ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Abstract Objectives Tumor-infiltrating lymphocytes (TILs) have recently emerged as a prognostic factor in breast cancer. In our previous study, we proposed that tumor stroma should also be considered in the calculation of TILs and we introduced tumor infiltration lymphocyte volume (TILV) in triple-negative breast cancer. Methods We assessed the disease-free survival predictive value of TILV in all subtypes of invasive breast carcinoma and compared the predictive value of TILV with TILs. Differences between disease-free survival curves were determined by using the log-rank test, and Kaplan-Meier survival plots were generated for both groups. Results TILV was significantly correlated with disease-free survival in both invasive ductal carcinoma (P = .03) and all subtypes of invasive breast carcinoma (P = .043), whereas TILs failed to show a statistical significance. Conclusions Tumor-stroma ratio needs to be considered in estimation of tumor immunity, and TILV adds more predictive power to TILs.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

scholarly journals Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

2019 ◽  
Vol 37 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Sherene Loi ◽  
Damien Drubay ◽  
Sylvia Adams ◽  
Giancarlo Pruneri ◽  
Prudence A. Francis ◽  
...  
Keyword(s):  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Proportional Hazards ◽  
Prognostic Information ◽  
Free Survival ◽  
Node Negative ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

scholarly journals Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

2020 ◽  
Author(s):  
Pooja Vaid ◽  
Anirudha Puntambekar ◽  
Rituja Banale ◽  
Ruhi Reddy ◽  
Rohini Unde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Stromal Tumor ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Transglutaminase II expression in invasive ductal carcinomas.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 34-34
Author(s):  
Jasmeet Sunny Assi ◽  
Gunjan Srivastava ◽  
Ajay Matta ◽  
Martin Chang ◽  
Ranju Ralhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Tumor Stroma ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Ductal Carcinomas ◽  
Disease Free

34 Background: Molecular markers for predicting breast cancer patients at high risk of recurrence are urgently needed for more effective disease management. The impact of alterations in extracellular matrix components on tumor aggressiveness is under intense investigation. Overexpression of Transglutaminase 2 (TG2), a multifunctional enzyme, in cancer cells impacts epithelial mesenchymal transition and cancer stem cell phenotype, growth, invasion and interactions with tumor microenvironment. The objective of our study is to determine the clinical relevance of stromal TG2 overexpression and explore its potential to identify which IDCs are at high risk of recurrence. Methods: This retrospective study is based on immunohistochemical analysis of TG2 expression in 168 invasive ductal carcinomas with clinical, pathological and follow-up data available for up to 12 years. TG2 expression was correlated with clinical and pathological parameters as well as disease free survival (DFS) of breast cancer patients. Results: Stromal TG2 overexpression was observed in 97/168 (57.7%) invasive ductal carcinomas (IDC). Notably, IDC patients showing stromal TG2 accumulation had significantly reduced disease free survival (mean DFS = 110 months) in comparison with patients showing low expression (mean DFS = 130 months), as revealed by Kaplan-Meier survival analysis (p <0.001). In Cox multivariate regression analysis, TG2 accumulation in tumor stroma emerged as an independent risk factor for recurrence in IDC (p = 0.006, Hazard’s ratio, H.R. = 3.79). Conclusions: Accumulation of TG2 in tumor stroma is an independent risk factor for identifying breast cancer patients at high risk of recurrence. TG2 overexpression in tumor stroma may serve as a predictor of poor prognosis for IDC of the breast.

scholarly journals Prognostic Value of Tumor Infiltrating Lymphocytes in Nasopharyngeal Carcinoma Patients: Meta-Analysis

2021 ◽  
Vol 20 ◽  
pp. 153303382110342
Author(s):  
Birhanu Aberha Berele ◽  
Yuxiang Cai ◽  
Guifang Yang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cd4 Cells ◽  
Free Survival ◽  
Registration Number ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objective: To evaluate the prognostic value of tumor infiltrating lymphocytes (TILs) in nasopharyngeal carcinoma (NPC) patients. Method: Meta-analysis was performed on eligible studies that was identified by systematic searching of Google scholar, MEDLINE, CNKI, Scopus, PubMed, PMC, Embase and Web of Science databases. The study protocol was registered in International Platform of Registered Systematic Review and Meta-Analysis Protocols-INPLASY (registration number: INPLASY202160014). Databases were searched from inception to January 20, 2020 to identify eligible studies. Those studies that evaluated survival in the form of hazard ratio (HR) in TILs of NPC patients was analyzed. All statistical analysis was performed by using STATA version 16.0 software. Result: Fourteen studies with a total of 3025 patients was analyzed. The pooled result showed that high TILs was significantly associated with favorable overall survival (OS) (HR = 0.55; 95%CI = 0.39-0.77; P = 0.001) and disease free survival (DFS) (HR = 0.60; 95%CI = 0.44-0.81; P = 0.04). Interestingly, high intratumoral TILs had relatively better OS (HR = 0.45; 95%CI = 0.35-0.58; P = 0.006) than stromal TILs (HR = 0.59; 95%CI = 0.36-0.97; P = 0.03). Moreover, an increased level of CD4+ cells infiltration was correlated with favorable OS (HR = 0.4; 95%CI = 0.18-0.85; P = 0.01). CD3+, CD8+ and FoxP3+ lymphocyte’s better prognosis was not statistically significant for OS ( P = 0.09; P = 0.07; P = 0.52) and for DFS ( P = 0.13; P = 0.29) respectively. However, subgroup analysis of intratumoral CD3+ (HR = 0.48; 95%CI = 0.33-0.70; P = 0.05) and intratumoral CD8+ (HR = 0.32; 95%CI = 0.16-0.62; P = 0.001) was significantly associated with improved OS, but not significant in stromal CD3+ (HR = 0.66; 95%CI = 0.20-2.20; P = 0.62). Conclusion: TILs were variably correlated with better prognosis depending on their microanatomic location and subset of TILs in NPC patients. CD4+, intratumoral CD3+ and intratumoral CD8+ lymphocytes could predict favorable patient outcome which suggest that their role in mediating antitumor immune response could potentially be exploited in the treatment of NPC patients. Future large study on the prognostic value of microanatomic location of TILs is needed for confirmation.

scholarly journals Intratumoral immune cells expressing PD-1/PD-L1 and their prognostic implications in cancer: a meta-analysis

2018 ◽  
Vol 33 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Younghoon Kim ◽  
Xianyu Wen ◽  
Nam Yun Cho ◽  
Gyeong Hoon Kang
Keyword(s):  
Overall Survival ◽  
Immune Cells ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Survival ◽  
Tissue Sections ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Background: The prognostic value of immune cells expressing programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) in cancer are controversial, and the potential differential impact of using tissue microarrays and whole tissue sections to assess the positivity of immune cells has not been addressed. Methods: The current study included 30 eligible studies with 7251 patients that evaluated the relationship between tumor-infiltrating lymphocytes expressing PD-1/PD-L1 and overall survival and disease-free survival, or progression-free survival. Subgroup analysis was based on the tissue type of cancer and the type of tissue sampling (tissue microarray or whole tissue section). Results: In the meta-analysis, PD-1-positive and PD-L1-positive tumor-infiltrating lymphocytes had a positive effect on disease-free survival or progression-free survival (hazard ratio [HR] 0.732; 95% confidence interval [CI] 0.565, 0.947; and HR 0.727; 95% CI 0.584, 0.905, respectively). PD-L1-positive tumor-infiltrating lymphocytes had a positive impact on overall survival in studies using tissue microarray (HR 0.586; 95% CI 0.476, 0.721), but had a poor impact when only whole tissue sections were considered (HR 1.558; 95% CI 1.232, 1.969). Lung cancer was associated with good overall survival and disease-free survival (HR 0.639; 95% CI 0.491, 0.831; and HR 0.693; 95% CI 0.538, 0.891, respectively) for PD-1-positive tumor-infiltrating lymphocytes, and colorectal cancer showed favorable disease-free survival (HR 0.471; 95% CI 0.308, 0.722) for PD-L1-positive tumor-infiltrating lymphocytes. Conclusion: Immune cells expressing PD-1 and PD-L1 within tumors are associated with the prognosis. However, the correlation may vary among different tumor types and by the type of tissue sampling used for the assessment.

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