Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer

2015 ◽  
Vol 69 (5) ◽  
pp. 422-430 ◽  
Author(s):  
Hee Jin Lee ◽  
In Ah Park ◽  
In Hye Song ◽  
Su-Jin Shin ◽  
Joo Young Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Prognostic Significance ◽  
Lymphocytic Infiltration ◽  
Prognostic Information ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures ◽  
Infiltrating Lymphocytes ◽  
Disease Free

BackgroundTumour-infiltrating lymphocytes (TILs) have a strong prognostic significance, particularly in triple-negative breast cancer (TNBC). One important source of TILs in breast cancer is tertiary lymphoid structures (TLSs).ObjectiveTo carry out a histological analysis of surgically resected TNBC to identify the location of TLSs, the relationship between TLSs and TILs and their prognostic significance in TNBC.MethodsWe retrospectively analysed 769 patients with TNBC.ResultsTILs were defined as the percentage of stroma of invasive carcinoma infiltrated by lymphocytes. TLSs were mainly present within adjacent terminal duct lobular units and around in situ components. TNBC with higher levels of TILs showed a higher nuclear grade, lower lymphovascular invasion, less accompanying in situ component, a homogeneous growth pattern, necrosis in invasive areas, low levels of tumour stroma, high levels of peritumoral lymphocytic infiltration and moderate to abundant TLSs in adjacent tissue. TILs, the degree of peritumoral lymphocytic infiltration and adjacent TLSs were prognostic factors for disease-free and overall survival. Although the TIL level did not have a prognostic value in stage I, it added significant prognostic information for stages II and III. Conversely, patients with high levels of TILs did not show prognostic differences according to the pTNM stage. Patients with high levels of TILs (>60%) and moderate to abundant TLSs had significantly better disease-free survival than those with high levels of TILs but none or few TLSs.ConclusionsTLSs are frequently present in TNBC and are closely associated with TILs. TILs provide additional prognostic information in patients with TNBC with a higher pTNM stage.

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.

The prognostic significance of peritumoral tertiary lymphoid structures in breast cancer

2019 ◽  
Vol 68 (11) ◽  
pp. 1733-1745 ◽  
Author(s):  
Michael Sofopoulos ◽  
Sotirios P. Fortis ◽  
Christoforos K. Vaxevanis ◽  
Nectaria N. Sotiriadou ◽  
Niki Arnogiannaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Significance ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

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

2021 ◽  
Author(s):  
Ana Tečić Vuger ◽  
Robert Šeparović ◽  
Sanda Šitić ◽  
Ljubica Vazdar ◽  
Mirjana Pavlović ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Androgen Receptors ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Clinically Significant ◽  
Infiltrating Lymphocytes

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.

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