scholarly journals Intraobserver and Interobserver Agreement in the Scoring of PD-L1 (SP142) and Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancers

2021 ◽  
Vol 6 (2) ◽  
pp. 30-36
Author(s):  
David Jerome Ong ◽  
◽  
Pier Angeli Medina ◽  
Sarah Jane Datay-Lim ◽  
Elizabeth Ann Alcazaren
Keyword(s):  
Interobserver Agreement ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancers ◽  
Infiltrating Lymphocytes

scholarly journals Immunotherapeutic Approaches in Triple-Negative Breast Cancer: State of the Art and Future Perspectives

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Karima Oualla ◽  
Loay Kassem ◽  
Lamiae Nouiakh ◽  
Lamiae Amaadour ◽  
Zineb Benbrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Poor Outcomes ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It accounts for 15%–20% of all breast cancers and is associated with an aggressive evolution and poor outcomes with the majority of recurrences and deaths occurring in the first 5 years. Chemotherapy remains the mainstay of treatment in the absence of effective targets, but the good understanding of immune tumor microenvironment, the identification of immune-related targets, and the role of tumor-infiltrating lymphocytes (TILs) in TNBC has allowed to develop promising immunotherapeutic strategies for this unique subset of breast cancer. Recently, immunotherapy is being extensively explored in TNBC and clinical trials have shown promising results. In this article, we tried to explain the rationale and mechanisms of targeting the immune system in TNBC, to report the results from recent clinical trials that put immunotherapy as a new standard of care in TNBC in addition to ongoing trials and future directions in the next decade.

scholarly journals The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease

Oncotarget ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 6201-6212 ◽  
Author(s):  
Gero Brockhoff ◽  
Stephan Seitz ◽  
Florian Weber ◽  
Florian Zeman ◽  
Monika Klinkhammer-Schalke ◽  
...  
Keyword(s):  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Favorable Outcome ◽  
Breast Cancers ◽  
Infiltrating Lymphocytes

scholarly journals Automated Quantification of sTIL Density with H&E-Based Digital Image Analysis Has Prognostic Potential in Triple-Negative Breast Cancers

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3050
Author(s):  
Jeppe Thagaard ◽  
Elisabeth Specht Stovgaard ◽  
Line Grove Vognsen ◽  
Søren Hauberg ◽  
Anders Dahl ◽  
...  
Keyword(s):  
Image Analysis ◽  
Digital Image ◽  
Digital Image Analysis ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Cancer Type ◽  
Tumor Type ◽  
Breast Cancers ◽  
Automated Quantification ◽  
Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is an aggressive and difficult-to-treat cancer type that represents approximately 15% of all breast cancers. Recently, stromal tumor-infiltrating lymphocytes (sTIL) resurfaced as a strong prognostic biomarker for overall survival (OS) for TNBC patients. Manual assessment has innate limitations that hinder clinical adoption, and the International Immuno-Oncology Biomarker Working Group (TIL-WG) has therefore envisioned that computational assessment of sTIL could overcome these limitations and recommended that any algorithm should follow the manual guidelines where appropriate. However, no existing studies capture all the concepts of the guideline or have shown the same prognostic evidence as manual assessment. In this study, we present a fully automated digital image analysis pipeline and demonstrate that our hematoxylin and eosin (H&E)-based pipeline can provide a quantitative and interpretable score that correlates with the manual pathologist-derived sTIL status, and importantly, can stratify a retrospective cohort into two significant distinct prognostic groups. We found our score to be prognostic for OS (HR: 0.81 CI: 0.72–0.92 p = 0.001) independent of age, tumor size, nodal status, and tumor type in statistical modeling. While prior studies have followed fragments of the TIL-WG guideline, our approach is the first to follow all complex aspects, where appropriate, supporting the TIL-WG vision of computational assessment of sTIL in the future clinical setting.

Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy With or Without Carboplatin in Human Epidermal Growth Factor Receptor 2–Positive and Triple-Negative Primary Breast Cancers

2015 ◽  
Vol 33 (9) ◽  
pp. 983-991 ◽  
Author(s):  
Carsten Denkert ◽  
Gunter von Minckwitz ◽  
Jan C. Brase ◽  
Bruno V. Sinn ◽  
Stephan Gade ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Infiltrating Lymphocytes ◽  
Mrna Markers

Purpose Modulation of immunologic interactions in cancer tissue is a promising therapeutic strategy. To investigate the immunogenicity of human epidermal growth factor receptor 2 (HER2) –positive and triple-negative (TN) breast cancers (BCs), we evaluated tumor-infiltrating lymphocytes (TILs) and immunologically relevant genes in the neoadjuvant GeparSixto trial. Patients and Methods GeparSixto investigated the effect of adding carboplatin (Cb) to an anthracycline-plus-taxane combination (PM) on pathologic complete response (pCR). A total of 580 tumors were evaluated before random assignment for stromal TILs and lymphocyte-predominant BC (LPBC). mRNA expression of immune-activating (CXCL9, CCL5, CD8A, CD80, CXCL13, IGKC, CD21) as well as immunosuppressive factors (IDO1, PD-1, PD-L1, CTLA4, FOXP3) was measured in 481 tumors. Results Increased levels of stromal TILs predicted pCR in univariable (P < .001) and multivariable analyses (P < .001). pCR rate was 59.9% in LPBC and 33.8% for non-LPBC (P < .001). pCR rates ≥ 75% were observed in patients with LPBC tumors treated with PMCb, with a significant test for interaction with therapy in the complete (P = .002) and HER2-positive (P = .006), but not the TNBC, cohorts. Hierarchic clustering of mRNA markers revealed three immune subtypes with different pCR rates (P < .001). All 12 immune mRNA markers were predictive for increased pCR. The highest odds ratios (ORs) were observed for PD-L1 (OR, 1.57; 95% CI, 1.34 to 1.86; P < .001) and CCL5 (OR, 1.41; 95% CI, 1.23 to 1.62; P < .001). Conclusion Immunologic factors were highly significant predictors of therapy response in the GeparSixto trial, particularly in patients treated with Cb. After further standardization, they could be included in histopathologic assessment of BC.

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