Tumor-infiltrating lymphocytes as a prognostic factor in patients with stage I to III breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12042-e12042
Author(s):  
Eduardo Richardet ◽  
Luciana Paola Acosta ◽  
Martin Paradelo ◽  
Martin Pairola ◽  
Cecilia Di Tada ◽  
...  

e12042 Background: Current evidence makes reference to the potential role that tumor-infiltrating lymphocytes (TILs) as a prognostic factor in breast cancer and numerous types of tumors. Different studies have shown that the interaction with the immune response of the host is relevant to the response to chemotherapy. TILs are cell phenotype T CD3 +, which can, in turn, stratify in cytotoxic T lymphocytes (CD8), and regulatory T cells (CD4+ CD25+ FOXP3+).Our aim was to identify whether there was a relationship between TILs and SLE in patients with stage I to III breast cancer who have undergone chemotherapy adjuvant treatment. The secondary endpoint was to analyze the association between subtype infiltrating lymphocytes (CD4 and CD8) and SLE. Methods: Retrospective and analytical study in our institution IONC. Patients with stage I to III breast cancer was analized which had standard risk factors and required adjuvant treatment with chemotherapy. 87 patients completed with the selection criteria. The infiltration degree by H/E was evaluated and CD4 and CD8 by IHQ was marked. SLE was analyzed through the Kaplan-Meier method. Results: 87 samples were analyzed, in 46 patients (52,8 %) evidenced TILs and in 41 patients (47.12%) there were no TILs in their tumor samples. SLE was higher for those patients who had TILs with respect to those patients who did not have any TILs, 45.3 months as opposed to 30.85 months respectively (p: 0,038) and these differences were statistically different. In the TILi analysis, it could observed that 91% patients not revealed infiltrations in their tumor samples.When correlating CD4 and CD8 was carried out, 33% of the patients showed CD4 TILs in their tumor samples and 49.4% evidenced CD8 TILs. There were no SLE differences regarding the presence or the absence of CD4. The high number of CD8 was associated to a higher SLE; 39.06 months as opposed to 37.5 months, but these differences were not statistically different. Conclusions: We could conclude that patients who had showed TILs in their tumor samples had a higher SLE with respect to those who did not show any infiltration and this was statistically significant. There were no differences when samples were analyzed on the presence or absence of CD4 and CD8.

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4883
Author(s):  
Marcus Schmidt ◽  
Anne-Sophie Heimes

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Farzin Negahbani ◽  
Rasool Sabzi ◽  
Bita Pakniyat Jahromi ◽  
Dena Firouzabadi ◽  
Fateme Movahedi ◽  
...  

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.


2013 ◽  
Vol 31 (7) ◽  
pp. 860-867 ◽  
Author(s):  
Sherene Loi ◽  
Nicolas Sirtaine ◽  
Fanny Piette ◽  
Roberto Salgado ◽  
Giuseppe Viale ◽  
...  

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.


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