scholarly journals Clinical Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer

2021 ◽  
Author(s):  
Yuka Asano ◽  
Shinichiro Kashiwagi ◽  
Sae Ishihara ◽  
Koji Takada ◽  
Wataru Goto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Cell Activity ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Breast Cancers ◽  
Malignant Breast ◽  
Immune Response To Cancer ◽  
Infiltrating Lymphocytes

Abstract Purpose Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3, and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC). Methods A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry. Results There were 47 (26.6%) patients with high LAG-3 expression, 31 (17.5%) patients had high TIM-3 expression, and 32 (18.1%) patients had high OX-40 expression. The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p = 0.038) and HER2-enriched breast cancer (HER2BC) (p = 0.021), and the total number of pathological complete response (pCR) patients was greater (p < 0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p < 0.001) (p = 0.020). Moreover, on multivariate analysis also showed that low-LAG-3 expression status was an independent factor to predict the favorable prognosis (p = 0.014, HR = 8.124) (p = 0.048, HR = 10.400). Conclusions Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

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 Patient Age Associates With Tumor-Infiltrating Lymphocytes Density In Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Sae Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Patients ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

Abstract Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

scholarly journals Patient Age Associates with Tumor-Infiltrating Lymphocytes Density in Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Sae Ishihara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Patients ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

Abstract Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

scholarly journals Patient Age Associates with Tumor-Infiltrating Lymphocytes Density in Breast Cancer

2021 ◽  
Author(s):  
Koji Takada ◽  
Shinichiro Kashiwagi ◽  
Yuka Asano ◽  
Wataru Goto ◽  
Tamami Morisaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Patients ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Therapeutic Effects ◽  
Significant Difference ◽  
Pre Treatment ◽  
Infiltrating Lymphocytes

Abstract Background: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.

scholarly journals Practical Approach to Triple-Negative Breast Cancer

2017 ◽  
Vol 13 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Vijayakrishna K. Gadi ◽  
Nancy E. Davidson
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Management Strategies ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Epidermal Growth ◽  
Proven Method

Triple negative is a term applied to breast cancers that do not meaningfully express the estrogen or progesterone hormone receptors or overexpress the human epidermal growth factor receptor 2 tyrosine kinase. At present, the only proven method for systemic management of triple-negative breast cancer for both early-stage and metastatic settings is cytotoxic chemotherapy. Here, we provide a comprehensive review of management strategies that are best supported by available data. We also review recent advances most likely to affect treatment of triple-negative breast cancer in the coming years with particular emphasis on targeted agents, biologics, and immunotherapy.

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