scholarly journals Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis

Oncotarget ◽  
2016 ◽  
Vol 7 (28) ◽  
pp. 44288-44298 ◽  
Author(s):  
Ke Wang ◽  
Jianjun Xu ◽  
Tao Zhang ◽  
Dan Xue
Keyword(s):  
Breast Cancer ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Survival Outcome ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

Tumor infiltrating lymphocytes (TIL) to predict response to neoadjuvant chemotherapy in breast cancer: A systemic review and meta-analysis.

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 138-138 ◽  
Author(s):  
Yan Mao ◽  
Qing Qu ◽  
Yuzi Zhang ◽  
Junjun Liu ◽  
Kunwei Shen
Keyword(s):  
Breast Cancer ◽  
T Lymphocytes ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Pathological Response ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes ◽  
The Relationship

138 Background: Whether tumor-infiltrating lymphocytes (TILs) predict response to neoadjuvant chemotherapy (NAC) remains elusive. Methods: A systematic review and meta-analysis was undertook to establish the relationship between TIL and pathological complete response (pCR) rate in NAC of breast cancer. A PubMed and Web of Science literature search was designed. Studies were included, in which the predictive significance of intratumoral and/or stromal TIL, and/or CD3+, CD4+, CD8+, and FOXP3+ lymphocytes were determined . Pooled ORs and publication bias was evaluated by STATA software. Results: A total of 13 published studies (including 3,555 patients) were eligible. In pooled analysis, higher number of TIL in pre-treatment biopsy was correlated with higher pCR rate of neoadjuvant chemotherapy, and odds ratio (OR) was 3.82 (95% confidence interval (CI), 3.10-4.70), no matter tested in intratumor (OR=3.32, 95% CI: 2.52-4.37), in stroma (OR=4.15,95% CI: 2.94-5.86), or in combined sites (OR=8.98, 95% CI: 3.79,21.30). Moreover, TIL predicts higher pCR rate in triple negative (OR=5.03,95% CI: 2.31-10.97) and HER2+ (OR=5.54,95% CI: 1.39-22.12) patients, but not in hormonal receptor (HR) +/HER2- patients (OR=2.57, 95% CI: 0.20-33.24). For TIL subsets, CD8+ T-lymphocytes predict better pathological response to NAC no matter in pre- (OR=3.36,95%CI: 1.15-9.85) or post-NAC (OR=4.71,95%CI: 1.29-17.27) tissue, while FOXP3+ T-lymphocytes have similar predictive roles only when tested after NAC (OR=4.26, 95%CI: 1.83-9.92).With limited study, the predictive role of CD3+ and CD4+T-lymphoctes were unclear, more perspective studies were needed in future to establish the relationship. Conclusions: High level of TIL in pre-treatment biopsy could be a good marker indicates better pathological response to NAC in triple-negative and HER2+ breast cancer patients. Different subsets have different predictive roles in the pCR rate to NAC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes and different subtypes of breast cancer to increase the robustness of the analyses.

scholarly journals Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4883
Author(s):  
Marcus Schmidt ◽  
Anne-Sophie Heimes
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes

The role of the immune system in breast cancer has been debated for decades. The advent of technologies such as next generation sequencing (NGS) has elucidated the crucial interplay between somatic mutations in tumors leading to neoantigens and immune responses with increased tumor-infiltrating lymphocytes and improved prognosis of breast cancer patients. In particular, triple-negative breast cancer (TNBC) has a higher mutational burden compared to other breast cancer subtypes. In addition, higher levels of tumor-associated antigens suggest that immunotherapies are a promising treatment option, specifically for TNBC. Indeed, higher concentrations of tumor-infiltrating lymphocytes are associated with better prognosis and response to chemotherapy in TNBC. An important target within the cancer immune cell cycle is the “immune checkpoint”. Immune checkpoint inhibitors (ICPis) block the interaction of certain cell surface proteins that act as “brakes” on immune responses. Recent studies have shown that ICPis improve survival in both early and advanced TNBC. However, this comes at the price of increased toxicity, particularly immune-mediated toxicity. As an alternative approach, individualized mRNA vaccination strategies against tumor-associated neoantigens represent another promising approach leading to neoantigen-specific immune responses. These novel strategies should help to improve treatment outcomes, especially for patients with triple negative breast cancer.

scholarly journals PathoNet introduced as a deep neural network backend for evaluation of Ki-67 and tumor-infiltrating lymphocytes in breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Farzin Negahbani ◽  
Rasool Sabzi ◽  
Bita Pakniyat Jahromi ◽  
Dena Firouzabadi ◽  
Fateme Movahedi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Deep Learning ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Detection ◽  
Ki 67 ◽  
Link Type ◽  
Proposed Model ◽  
Response To Chemotherapy ◽  
Individual Variations ◽  
Infiltrating Lymphocytes

AbstractThe nuclear protein Ki-67 and Tumor infiltrating lymphocytes (TILs) have been introduced as prognostic factors in predicting both tumor progression and probable response to chemotherapy. The value of Ki-67 index and TILs in approach to heterogeneous tumors such as Breast cancer (BC) that is the most common cancer in women worldwide, has been highlighted in literature. Considering that estimation of both factors are dependent on professional pathologists’ observation and inter-individual variations may also exist, automated methods using machine learning, specifically approaches based on deep learning, have attracted attention. Yet, deep learning methods need considerable annotated data. In the absence of publicly available benchmarks for BC Ki-67 cell detection and further annotated classification of cells, In this study we propose SHIDC-BC-Ki-67 as a dataset for the aforementioned purpose. We also introduce a novel pipeline and backend, for estimation of Ki-67 expression and simultaneous determination of intratumoral TILs score in breast cancer cells. Further, we show that despite the challenges that our proposed model has encountered, our proposed backend, PathoNet, outperforms the state of the art methods proposed to date with regard to harmonic mean measure acquired. Dataset is publicly available in http://shiraz-hidc.com and all experiment codes are published in https://github.com/SHIDCenter/PathoNet.

Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes in a Phase III Randomized Adjuvant Breast Cancer Trial in Node-Positive Breast Cancer Comparing the Addition of Docetaxel to Doxorubicin With Doxorubicin-Based Chemotherapy: BIG 02-98

2013 ◽  
Vol 31 (7) ◽  
pp. 860-867 ◽  
Author(s):  
Sherene Loi ◽  
Nicolas Sirtaine ◽  
Fanny Piette ◽  
Roberto Salgado ◽  
Giuseppe Viale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Lymphocytic Infiltration ◽  
Phase Iii ◽  
Cancer Trial ◽  
Risk Of Death ◽  
Node Positive ◽  
Response To Chemotherapy ◽  
Infiltrating Lymphocytes ◽  
Reduced Risk

Purpose Previous preclinical and clinical data suggest that the immune system influences prognosis and response to chemotherapy (CT); however, clinical relevance has yet to be established in breast cancer (BC). We hypothesized that increased lymphocytic infiltration would be associated with good prognosis and benefit from immunogenic CT—in this case, anthracycline-only CT—in selected BC subtypes. Patients and Methods We investigated the relationship between quantity and location of lymphocytic infiltrate at diagnosis with clinical outcome in 2009 node-positive BC samples from the BIG 02-98 adjuvant phase III trial comparing anthracycline-only CT (doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil [CMF] or doxorubicin plus cyclophosphamide followed by CMF) versus CT combining doxorubicin and docetaxel (doxorubicin plus docetaxel followed by CMF or doxorubicin followed by docetaxel followed by CMF). Readings were independently performed by two pathologists. Disease-free survival (DFS), overall survival (OS), and interaction with type of CT associations were studied. Median follow-up was 8 years. Results There was no significant prognostic association in the global nor estrogen receptor (ER) –positive/human epidermal growth factor receptor 2 (HER2) –negative population. However, each 10% increase in intratumoral and stromal lymphocytic infiltrations was associated with 17% and 15% reduced risk of relapse (adjusted P = .1 and P = .025), respectively, and 27% and 17% reduced risk of death in ER-negative/HER2-negative BC regardless of CT type (adjusted P = .035 and P = .023), respectively. In HER2-positive BC, there was a significant interaction between increasing stromal lymphocytic infiltration (10% increments) and benefit with anthracycline-only CT (DFS, interaction P = .042; OS, P = .018). Conclusion In node-positive, ER-negative/HER2-negative BC, increasing lymphocytic infiltration was associated with excellent prognosis. Further validation of the clinical utility of tumor-infiltrating lymphocytes in this context is warranted. Our data also support the evaluation of immunotherapeutic approaches in selected BC subtypes.

scholarly journals Prognostic value of tumor-infiltrating lymphocytes in patients with triple-negative breast cancer: a systematic review and meta-analysis

2019 ◽  
Author(s):  
Guoxuan Gao ◽  
Zihan Wang ◽  
Xiang Qu ◽  
Zhongtao Zhang
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Triple Negative ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Risk Of Bias ◽  
Statistical Association ◽  
Long Term Prognosis ◽  
Infiltrating Lymphocytes

Abstract Objective The objective of this systematic review and meta-analysis is to determine prognostic roles of the total tumor-infiltrating lymphocytes (TILs) or subtypes of TILs (CD4+, CD8+, and FOSP3+) for patients with triple-negative breast cancer (TNBC).Methods A systematic literature search was conducted in the databases of MEDLINE, EMBASE, and Web of Science to identified eligible articles before August 2019. Study screening, data extraction, and risk of bias were performed by two independent reviewers. Risk of bias on study level was assessed using an approach based on the ROBINS I tool and the Quality In Prognosis Studies (QUIPS) tool. We performed meta-analyses to obtain a pooled estimate of the prognostic role of TILS using Review Manager 5.3.Results There was total of 37 studies included in the final analysis. Compared to TNBC patients with poor TILs, TNBC patients with rich TILs had a higher pCR to treatments (OR 2.14, 95% CI 1.43-3.19). Along with per 10% increase of the TILs, patients with TNBC had an increased pCR (OR 1.09, 95% CI 1.02-1.16). Compared to TNBC patients with poor TILs, patients with rich TILs had a better OS (HR 0.58, 95% CI 0.48-0.71) and DFS (HR 0.66, 95% CI 0.57-0.76). Addition to, along with a continuous increase of the TILs, patients with TNBC had improved OS (HR 0.90, 95% CI 0.87-0.93) and DFS (HR 0.92, 95% CI 0.90-0.95) as well. CD4+TILs subgroup (rich vs. poor) showed a better OS (HR 0.49, 95%CI 0.32-0.76) and DFS (HR 0.54, 95%CI 0.36-0.80). CD8+TILs subgroup (rich vs. poor) showed a better DFS (HR 0.55, 95% CI 0.38-0.81), but no statistical association was found with OS (HR 0.70, 95% CI 0.46-1.06). FOXP3+TILs subgroup (rich vs. poor) showed a better DFS (HR 0.50, 95% CI 0.33-0.75), but no statistical association was found with OS (HR 1.28, 95% CI 0.24-6.88).Conclusion TNBC with higher levels of TILs showed better short-term and long-term prognosis. The phenotypes of TILs (CD4+TILs, CD8+TILs, and FOXP3+TILs) had positive prediction for long-term prognosis for TNBC.

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