scholarly journals Histopathological Evaluation of Tumor-Infiltrating Lymphocytes (TILs) as Predictive Biomarker for Hormone Receptors Status, Proliferative Activity and Clinical Outcome in Her-2 Positive Breast Cancer

2021 ◽  
Vol 11 (15) ◽  
pp. 6788
Author(s):  
Giuseppe Angelico ◽  
Giuseppe Broggi ◽  
Rosario Caltabiano ◽  
Angela Santoro ◽  
Saveria Spadola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Biomarker ◽  
Nuclear Staining ◽  
Ki 67 ◽  
Stromal Tissue ◽  
Her 2 ◽  
Infiltrating Lymphocytes ◽  
Positive Breast Cancer

Background: In the present study, we evaluated the prognostic value of TILs as well their relation with clinicopathological factors in patients affected by HER-2 positive breast cancer. Methods: We evaluated 47 patients with a histologically confirmed diagnosis of invasive breast carcinoma showing an immunohistochemically confirmed (score 3+) amplification of the c-erbB-2 gene for the presence of TILs and categorized in three predefined groups of low (0–10% immune cells in stromal tissue within the tumor), intermediate (11–40%), and high TILs (>40%). Results: Low, intermediate and high TILs were found in 17/47 (36%), 23/47 (49%) and 7/47(15%) cases, respectively. It was found that 6/47 cases treated with adjuvant chemotherapy plus trastuzumab underwent progression of the disease; none of these cases exhibited high TILs. It was found that 12/47 patients with a prognostically unfavorable stage of III and IV showed low and intermediate levels of TILs, while high TILs were never observed. A significant association between intermediate/high-levels of TILs, elevated KI 67 index and hormone receptors nuclear staining was observed. High concordance in TILs distribution was observed between preoperative breast biopsies and surgical samples. Conclusions: We observed a positive correlation between the TILs and the response to both adjuvant and neoadjuvant treatments in HER-2 positive BC. High TILs were also related to increased KI-67 index and to the expression of hormone receptors.

Correlation between magnetic resonance imaging and the level of tumor-infiltrating lymphocytes in patients with estrogen receptor-negative HER2-positive breast cancer

2019 ◽  
Vol 61 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Woo Jung Choi ◽  
Youyeon Kim ◽  
Joo Hee Cha ◽  
Hee Jung Shin ◽  
Eun Young Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multiple Logistic Regression Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Multiple Logistic Regression ◽  
Resonance Imaging ◽  
Her2 Positive ◽  
Peak Enhancement ◽  
Her 2 ◽  
Infiltrating Lymphocytes ◽  
Positive Breast Cancer

Background High levels of tumor-infiltrating lymphocytes (TILs) are associated with improved prognosis and response to therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Purpose This study investigated the associations between TIL levels and magnetic resonance imaging (MRI) findings in patients with estrogen receptor (ER)-negative HER-2 positive breast cancer. Material and Methods This study included 110 consecutive patients with surgically confirmed ER-negative HER2-positive breast cancers who underwent preoperative MRI from January to December 2015. Images of all lesions were reviewed in accordance with the BI-RADS lexicon by radiologists blinded to clinicopathologic findings. Tumor kinetic features were acquired by computer-aided diagnosis (CAD). Patients were divided into three TIL groups: low (<10%); intermediate (10–50%); and high (>50%). Associations between TIL levels and clinicopathologic and imaging features were evaluated; independent predictors of high and low TIL were identified by multiple logistic regression analysis. Results The 110 patients included 29 (26.4%) with low, 45 (40.9%) with intermediate, and 36 (32.7%) with high TIL levels. Multiple logistic regression analysis showed that older age (odds ratio [OR] = 1.08; P = 0.017), high peak enhancement (OR = 1.01; P = 0.019), positive CK5/6 (OR = 4.36; P = 0.024), and low Ki-67 (OR = 14.29; P = 0.037) were significantly associated with low TILs; low peak enhancement (OR = 1.01; P = 0.020) was significantly associated with high TILs. Conclusion MRI features may predict TIL levels in patients with ER-negative HER-2 positive breast cancer, enhancing the ability to diagnose and treat these patients.

scholarly journals High expression of E-cadherin and Ki-67 associated with functional/dysfunctional phenotypes of tumor-infiltrating lymphocytes among Chinese patients with operable breast cancer

2018 ◽  
Vol 46 (12) ◽  
pp. 5219-5227 ◽  
Author(s):  
Ruibin Wang ◽  
Feng Shi ◽  
Lin Zhao ◽  
Yanjie Zhao ◽  
Guangjiang Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Infiltrating Lymphocytes ◽  
Cross Sectional Study ◽  
Clinicopathological Features ◽  
Chinese Patients ◽  
Ki 67 ◽  
Cross Sectional ◽  
Cell Counts ◽  
Infiltrating Lymphocytes ◽  
E Cadherin

Objective Breast cancer has become the most common cancer in women in China, and the clinicopathological features differ from those in Western patients. This study was performed to investigate the distribution of programmed cell death protein 1 (PD-1)+/PD-1− tumor-infiltrating lymphocytes (TILs) and its association with clinicopathological features among Chinese patients with breast cancer. Methods In total, 133 consecutive patients with primary breast cancer were recruited into this cross-sectional study from 2012 to 2013. TILs were measured by cell counts under high-power fields (HPFs). Immunohistochemistry was used to detect PD-1 expression on tumor-infiltrating lymphocytes in the microenvironment. Results The median cell counts of the overall TILs, PD-1+ TILs, and PD-1− TILs were 80, 18, and 55/HPF, respectively. The number of PD-1− TILs was significantly lower in older than younger patients (50 vs. 60/HPF). Patients with positive E-cadherin expression had more PD-1− TILs than patients with negative E-cadherin expression (57 vs. 27/HPF). The Ki-67 index was positively correlated with the cell counts of PD-1+ TILs, and the correlation coefficient was 0.29. Conclusions PD-1 expression on TILs had different clinicopathological features in Chinese patients with breast cancer. E-Cadherin expression was associated with PD-1− TILs; however, Ki-67 expression was associated with PD-1+ TILs.

scholarly journals Cell Counts, rather than Proportion, of CD8/PD-1 Tumor-Infiltrating Lymphocytes in a Tumor Microenvironment Associated with Pathological Characteristics of Chinese Invasive Ductal Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Qingkun Song ◽  
Feng Shi ◽  
Maya Adair ◽  
Hong Chang ◽  
Xiudong Guan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Axillary Lymph Node ◽  
Tumor Infiltrating Lymphocytes ◽  
Axillary Lymph Node Metastasis ◽  
Axillary Lymph ◽  
Ki 67 ◽  
Invasive Ductal Breast Cancer ◽  
Cell Counts ◽  
Infiltrating Lymphocytes

Objective. This study is aimed at investigating the association of exhausted CD8+ tumor-infiltrating lymphocytes with clinic-pathological factors. Methods. 133 patients diagnosed with primary invasive ductal breast cancer were recruited into the cross-sectional study consecutively. Immunohistochemistry was used to detect biomarker expression on formalin-fixed and paraffin-embedded sections. Double staining of CD8 and PD-1 was conducted on lymphocytes. Results. The proportion of CD8+/PD-1- TILs was 16% among patients with axillary lymph node metastasis, significantly lower than those without metastasis (24%). The expression of CK7, CK20, or Ki-67 was not related with the proportion of phenotypes of CD8/PD-1 TILs. Younger patients had more cell counts of CD8+/PD-1- TILs than elderly patients (18/HPF vs. 9/HPF, p<0.05). Patients with axillary lymph node metastasis had less CD8+/PD-1- TILs than those without metastasis (11/HPF vs. 27/HPF, p<0.05). Median counts of CD8+/PD-1- TILs among patients with CK20 and E-Cad expression were 33/HPF and 14/HPF, significantly higher than those among patients with negative CK20 (16/HPF) and E-Cad expression (6/HPF). Ki-67 index had a significant correlation with cell counts of CD8+/PD-1+ TILs and CD8+/PD-1- TILs, and the correlation coefficients were 0.19 and 0.21 (p<0.05), respectively. Conclusion. The proportion of CD8+/PD-1- TILs was related with metastatic status of the axillary lymph node but cell counts of CD8+/PD-1- TILs were related with metastatic status of the axillary lymph node and expression of CK7, CK20, E-Cad, and Ki-67. Absolute cell counts, not proportion of CD8/PD-1 TILs, were more likely to distinguish clinic and pathologic characteristics of breast cancer.

scholarly journals Estrogen Receptor Positive Breast Cancer with High Expression of Androgen Receptor has Less Cytolytic Activity and Worse Response to Neoadjuvant Chemotherapy but Better Survival

2019 ◽  
Vol 20 (11) ◽  
pp. 2655 ◽  
Author(s):  
Maiko Okano ◽  
Masanori Oshi ◽  
Ali Linsk Butash ◽  
Mariko Asaoka ◽  
Eriko Katsuta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Cytolytic Activity ◽  
Er Positive ◽  
Infiltrating Lymphocytes ◽  
Response To Neoadjuvant Chemotherapy ◽  
Positive Breast Cancer

Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives (p < 0.001, p < 0.001, respectively) and it correlated with ER expression (R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = −2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC (p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC.

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