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 Case Report: A Case Study Documenting the Activity of Atezolizumab in a PD-L1-Negative Triple-Negative Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Fara Brasó-Maristany ◽  
Miriam Sansó ◽  
Nuria Chic ◽  
Débora Martínez ◽  
Blanca González-Farré ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Genomic Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Durable Response ◽  
Tumor Mutational Burden

The immune checkpoint inhibitor atezolizumab is approved for PD-L1-positive triple-negative breast cancer (TNBC). However, no activity of atezolizumab in PD-L1-negative TNBC has been reported to date. Here, we present the case study of a woman with TNBC with low tumor infiltrating lymphocytes and PD-L1-negative disease, which achieved a significant response to atezolizumab monotherapy and durable response after the combination of atezolizumab and nab-paclitaxel. The comprehensive genomic analysis that we performed in her tumor and plasma samples revealed high tumor mutational burden (TMB), presence of the APOBEC genetic signatures, high expression of the tumor inflammation signature, and a HER2-enriched subtype by the PAM50 assay. Some of these biomarkers have been shown to independently predict response to immunotherapy in other tumors and may explain the durable response in our patient. Our work warrants further translational studies to identify biomarkers of response to immune checkpoint inhibitors in TNBC beyond PD-L1 expression and to better select patients that will benefit from immunotherapy.

The Use of Atezolizumab + Nab-Paclitaxel for Women with PD- L1 Positive Advanced Triple-Negative Breast Cancer

2021 ◽  
Vol 8 (7) ◽  
pp. 36-43
Author(s):  
Vahideh Beygi Rezagholi ◽  
Sheby Elsa George ◽  
Gouthami. U
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Growth Factor Receptor ◽  
Progesterone Receptors ◽  
Tumor Infiltrating Lymphocytes

Triple-negative breast cancer (TNBC) is an uncommon subtype of breast cancer that constitutes 15-20% of cases which has a poorer prognosis and lower survival rates (approximately 18 months or less with available treatments) compared to other types of breast cancer. As the name suggests, TNBC is immunohistologically marked by the lack of expression of factors namely estrogen receptors (ER), progesterone receptors (PR), and lack of overexpression and/or amplification of the human epidermal growth factor receptor 2 (HER2)/NEU gene. TNBC is characterized by high grades of Tumor-Infiltrating lymphocytes (TILs), programmed-death ligand 1 (PD-L1) expression, and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as observed in other cancers too. Hence, metastatic TNBC (mTNBC) therapy focuses on the advancement of immune checkpoint inhibitors which block the above immune checkpoint proteins. The use of Atezolizumab (anti-PD-L1) in combination with nab-paclitaxel (chemotherapy agent) has been marked as a relevant advance in the treatment of metastatic, PD-L1-positive TNBC. It is better to consider advanced and approved diagnostic (VENTANA PD-L1 SP142 assay) in patients who get benefit from treatment with Atezolizumab plus nab-paclitaxel. Keywords: Triple Negative Breast Cancer (TNBC), Atezolizumab, Nab-paclitaxel, Chemotherapy.

Tumor infiltrating lymphocytes (TILs) and the expression of programmed death ligand 1 (PD-L1) as predictors for the response rate of preoperative systemic therapy (PST) and prognosis in triple-negative breast cancer (TNBC).

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 157-157
Author(s):  
Nobumoto Tomioka ◽  
Manabu Azuma ◽  
Kanako Hagio ◽  
Mayuko Ikarashi ◽  
Masako Satoh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Systemic Therapy ◽  
Immune Checkpoint ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
The Status ◽  
Infiltrating Lymphocytes

157 Background: The status of tumor infiltrating lymphocytes (TILs) is known to be prognostic for triple negative breast cancer (TNBC) due to its correlation with chemosensitivity. Moreover, to regulate the pathway of immune-checkpoint molecules is also expected to improve the prognosis of TNBC. The relevancy of these two factors could be attractive concerning on the immune interaction which might play an important role in the prognosis of TNBC. Methods: Patients with TNBC are 277 among 2371 who were underwent surgery between January 2002 and December 2011. Out of 90 patients received preoperative systemic therapy (PST), 32 patients’ specimens of core needle biopsy were available for review for TILs. The TILs was scored as “% stromal” by pathologist who feels comfortable with through the scan for single whole section according to the recommendations by an International TILs Working Group 2014. The expression of programmed death ligand 1 (PD-L1) was assessed by immunohistochemistry, which was defined 3 stages as negative or positive (weak or strong) by the pathologist in our facility. The statistical analysis for variance was done by Mann-Whitney U-test or Kruskal-Wallis test, and for survival by Kaplan Meier method was evaluated by Logrank test. Results: TILs’ score was defined as follows (%; numbers of patients): (5; 2), (10; 8), (20; 9), (30; 7), (40; 1), (50; 1), (60; 1), (70; 2), (80; 0), (90; 1). Statistical validations for variance of TILs’ score were significant on the regression rate of tumor size: (T-pT)/T; < 2/3 v.s. 2/3 < (p= 0.0097), and pathological therapeutic grade: 1 vs 2 or 3 (p= 0.0285). When we set the threshold at 30% of TILs’ score, DFS with TILs’ score < 30% was worse significantly (p= 0.0383) but not on OS (p= 0.0772). Unfavorable group on DFS (TILs’ score < 30%) was divided again into two groups by the status of PD-L1 significantly (negative or weak v.s. strong; p= 0.0319). Conclusions: The status of TILs and PD-L1 could elucidate the candidate for the therapeutic approaches to immune-checkpoint molecules, which could make improvement of the prognosis of TNBC.

scholarly journals Systemic immune reaction in axillary lymph nodes adds to tumor-infiltrating lymphocytes in triple-negative breast cancer prognostication

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Fangfang Liu ◽  
Thomas Hardiman ◽  
Kailiang Wu ◽  
Jelmar Quist ◽  
Patrycja Gazinska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Responses ◽  
Lymph Nodes ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Her2 Positive ◽  
Local Immunity ◽  
Infiltrating Lymphocytes

AbstractThe level of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative (TNBC) and HER2-positive breast cancers convey prognostic information. The importance of systemic immunity to local immunity is unknown in breast cancer. We previously demonstrated that histological alterations in axillary lymph nodes (LNs) carry clinical relevance. Here, we capture local immune responses by scoring TILs at the primary tumor and systemic immune responses by recording the formation of secondary follicles, also known as germinal centers, in 2,857 cancer-free and involved axillary LNs on haematoxylin and eosin (H&E) stained sections from a retrospective cohort of 161 LN-positive triple-negative and HER2-positive breast cancer patients. Our data demonstrate that the number of germinal center formations across all cancer-free LNs, similar to high levels of TILs, is associated with a good prognosis in low TILs TNBC. This highlights the importance of assessing both primary and LN immune responses for prognostication and for future breast cancer research.

scholarly journals Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes

2021 ◽  
Author(s):  
H. Kuroda ◽  
T. Jamiyan ◽  
R. Yamaguchi ◽  
A. Kakumoto ◽  
A. Abe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cytotoxic T Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Tumor Associated Macrophages ◽  
Free Survival ◽  
Infiltrating Lymphocytes

Abstract Purpose Immune cells such as cytotoxic T cells, helper T cells, B cells or tumor-associated macrophages (TAMs) contribute to the anti-tumor response or pro-tumorigenic effect in triple negative breast cancer (TNBC). The interrelation of TAMs, T and B tumor-infiltrating lymphocytes (TILs) in TNBC has not been fully elucidated. Methods We evaluated the association of tumor-associated macrophages, T and B TILs in TNBC. Results TNBCs with a high CD68+, CD163+ TAMs and low CD4+, CD8+, CD20+ TILs had a significantly shorter relapse-free survival (RFS) and overall survival (OS) than those with low CD68+, CD163+ TAMs and high CD4+, CD8+, CD20+ TILs. TNBCs with high CD68+ TAMs/low CD8+ TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD68+ TAMs/high CD8+ TILs, low CD68+ TAMs/high CD8+ TILs, and low CD68+/low CD8+. TNBCs with high CD163+ TAMs/low CD8+, low CD20 + TILs showed a significantly shorter RFS and OS and a significantly poorer prognosis than those with high CD163+ TAMs/high CD8+ TILs and high CD163+ TAMs /high CD20+ TILs. Conclusions Our study suggests that TAMs further create an optimal tumor microenvironment (TME) for growth and invasion of cancer cells when evasion of immunoreactions due to T and B TILs occurs. In TNBCs, all these events combine to affect prognosis. The process of TME is highly complex in TNBCs and for an improved understanding, larger validation studies are necessary to confirm these findings.

Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer

2015 ◽  
Vol 7 (4) ◽  
pp. 232-241
Author(s):  
Koo Si-Lin ◽  
Loh Kiley ◽  
Sulastri Kamis ◽  
Jabed Iqbal ◽  
Rebecca Dent ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Prognostic Value ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes
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