PD-L1 expression in tumor lesions and soluble PD-L1 serum levels in patients with breast cancer: TNBC versus TPBC

2021 ◽  
pp. 1-9
Author(s):  
Parvaneh Yazdanpanah ◽  
Ali Alavianmehr ◽  
Abbas Ghaderi ◽  
Ahmad Monabati ◽  
Mehdi Montazer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Healthy Women ◽  
Grade 3 ◽  
Anti Tumor Activity ◽  
Tnbc Subtype ◽  
Cell Death Protein

BACKGROUND: Block of programmed cell death protein 1 (PD-1) interaction with its ligand, PD-L1, enhances anti-tumor activity. OBJECTIVES: We aimed to assess the association between PD-L1 expression in tumor cells and CD8+ tumor infiltrating T cells (TILs) as well as soluble (s)PD-L1 serum levels in patients with triple negative breast cancer (TNBC) compared to triple positive (TPBC). METHODS: A total of 113 tumor sections and 133 serum samples were available from 144 patients with breast cancer (72 TNBC and 72 TPBC). Dual immunohistochemistry staining was applied to determine differential PD-L1 expression in tumor cells and CD8+ TILs. Soluble PD-L1 serum levels were also evaluated in patients compared to 40 healthy women by ELISA method. RESULTS: Despite TPBC patients which were mostly grades 1/2, TNBC patients were grade 3 (72% versus 66.7%, P < 0.001). Most of the TNBC patients were stages I/II, whereas most of the TPBC patients were stages III/IV (57.3% versus 68.3%,P = 0.005). There was no difference in tumor size and metastasis between TNBC and TPBC patients, although the number of involved lymph nodes was significantly more in TPBC patients (P = 0.0012). PD-L1 expression was detected in 11.5% of samples mostly in TNBC subtype and was associated with advanced grades (P = 0.039). There was no relationship between PD-L1 expression and tumor stage. PD-L1 expression in CD8+ TILs was nonsignificantly higher than tumor cells. Serum levels of sPD-L1 showed no difference between patients and healthy women. We found no correlation between PD-L1 expression in tumor lesions and serum levels of sPD-L1 in patients. CONCLUSION: PD-L1 expression was more detected in our patients with TNBC. It seems that, these patients who are resistant to standard chemotherapy regimens may get benefit from PD-L1 inhibition therapy and because of its low serum levels, sPD-L1 cannot interfere with this therapy.

Transforming Growth Factor Beta 1 Serum Levels in Patients with Preinvasive and Invasive Lesions of the Breast

2004 ◽  
Vol 19 (3) ◽  
pp. 236-239 ◽  
Author(s):  
A. Lebrecht ◽  
C. Grimm ◽  
G. Euller ◽  
E. Ludwig ◽  
E. Ulbrich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Serum Levels ◽  
Breast Carcinogenesis ◽  
Receptor Status ◽  
Healthy Women ◽  
Growth Factor Beta ◽  
Tgf Β1

Transforming growth factor beta (TGF-β)1 is thought to be involved in breast carcinogenesis. TGF-β1 acts in an antiproliferative manner in the early stages of breast carcinogenesis, but promotes tumor progression and metastases in the advanced stages of the disease. No data have been published on serum TGF-β1 in breast cancer. We investigated TGF-β1 serum levels in patients with breast cancer (n=135), ductal carcinoma in situ (DCIS) I to III (n=67) or fibroadenoma (n=35), and in healthy women (n=40) to determine its value as a differentiation marker between malignant, pre-invasive and benign diseases and as a predictive marker for metastatic spread. Median (range) TGF-β1 serum levels in patients with breast cancer, DCIS I-III or benign breast lesions and in healthy women were 48.8 (18–82.4) pg/mL, 45.3 (26.9–58.3) pg/mL, 47.2 (17.2–80.5) pg/mL and 51.6 (30.9–65.1) pg/mL, respectively (p=0.2). In breast cancer patients TGF-β1 serum levels showed no statistically significant correlation with tumor stage, lymph node involvement, histological grade, estrogen receptor status and progesterone receptor status. Our data fail to indicate any correlation between serum TGF-β1 levels and clinicopathological parameters of breast diseases. Serum TGF-β1 levels do not provide clinical information in addition to established tumor markers.

scholarly journals Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer

2019 ◽  
Vol 8 (5) ◽  
pp. 612 ◽  
Author(s):  
Renaud Sabatier ◽  
Emmanuelle Charafe-Jauffret ◽  
Jean-Yves Pierga ◽  
Hervé Curé ◽  
Eric Lambaudie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.

Comparison of CA 15-3 and CEA in diagnosis and monitoring of breast cancer

1989 ◽  
Vol 4 (4) ◽  
pp. 207-214 ◽  
Author(s):  
F. Safi ◽  
I. Kohler ◽  
E. Röttinger ◽  
P. Suhr ◽  
H. G. Beger
Keyword(s):  
Breast Cancer ◽  
Serum Levels ◽  
Tumor Stage ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Benign Diseases ◽  
Breast Cancer Metastases ◽  
Normal Limits ◽  
Cancer Metastases ◽  
Tumor Associated Antigen

In order to assess the utility of the tumor-associated antigen CA15-3 in the diagnosis of breast cancer, this new tumor marker was measured pre-operatively in 1342 patients. This group comprised 509 patients with malignant disease (134 with breast cancer and 375 with other malignancies not involving the breast) and 833 patients with benign surgical diseases (95 patients with fibroadenoma of the breast, 738 with other benign diseases). The results were compared with those for carcino-embryonic antigen (CEA) in the diagnosis of breast cancer. CA15-3 was above the normal limits of 25 U/ml in 31% of the patients with breast cancer, in 22% of patients with other malignancies, and in 9% of patients with benign diseases. CEA was elevated in 26% of patients with breast cancer (> 3ng/ml). CA15-3 levels were above 50 U/ml in 13% of the breast cancer patients, in 6%) of patients with other malignancies, and in 0.2% of the patients with benign diseases. There was a good correlation between CA 15-3 level and tumor stage in breast cancer. CA 15-3 serum levels were over 50 U/ml in respectively 0%, 2%, 13%, and 73% of the patients with stages I, II, III, and IV. CA 15-3 and CEA were also determined in 671 patients who had received initial curative surgery of breast cancer, and who regularly attended our follow-up clinic. CA15-3 was found to be more sensitive than CEA in detecting recurrences of breast cancer. In the post-care period, carcinoma recurred in 205 patients. Of these 73% had CA15-3 concentrations above 25 U/ml, whereas only 50% had CEA values above 3 ng/ml (p< 0.0001). Although neither CA15-3 nor CEA are sensitive enough for the screening and diagnosis of early breast cancer, CA 15-3 is superior to CEA in the detection of breast cancer metastases.

Evaluation of Chromogranin a Expression in Serum and Tissues of Breast Cancer Patients

2001 ◽  
Vol 16 (4) ◽  
pp. 268-272 ◽  
Author(s):  
L. Giovanella ◽  
M. Marelli ◽  
L. Ceriani ◽  
G. Giardina ◽  
S. Garancini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chromogranin A ◽  
Neuroendocrine Differentiation ◽  
Serum Levels ◽  
Tumor Stage ◽  
Lymph Node Status ◽  
Ca 15.3 ◽  
Tumor Histology ◽  
The Relationship ◽  
Extent Of Disease

Human chromogranin A (CgA) is a member of the granin family and is widely distributed in large dense core granules of endocrine and neuroendocrine cells. A variety of non-neuroendocrine carcinomas arising in various tissues show patterns of neuroendocrine differentiation. Expression of CgA has been documented in epithelial cells of normal mammary gland as well as in breast cancers, and elevation of serum CgA has been detected in patients with breast cancer. Our study was undertaken to evaluate the relationship between serum CgA levels and neuroendocrine features in breast cancer. In addition, we evaluated the expression of serum CgA in patients affected by breast cancer compared to controls and the relationship between serum CgA and tumor histology, extent of disease, lymph node status, tumor stage and serum CA 15.3 levels. We enrolled 266 patients with infiltrating ductal or lobular breast carcinoma and a group of 100 age-matched healthy women serving as controls. Serum CgA and CA 15.3 were assayed by specific immunoradiometric methods. The overall sensitivity of CgA and CA 15.3 was 0.06 and 0.34, respectively (χ219.1, p<0.0005). No relationship was found between serum levels of CgA and tumor histology, extent of disease, lymph node status or tumor stage while serum levels of CA 15.3 were strongly correlated with all these variables but tumor histology. No relationship was found between serum levels of CgA and CA 15.3. Immunostaining against CgA, CgB, NSE and synaptophysin was performed on primary tumor tissue of 14 serum CgA-positive and 24 serum CgA-negative patients and was negative in all cases. We also evaluated eight cases of pathologically-proven neuroendocrine breast cancer: only four and two of these showed positive CgA immunostaining and increased serum CgA concentration, respectively. In conclusion, serum CgA assay offers no additional information regarding the presence, the extent and the histology of breast cancer compared to the CA 15.3 assay. Moreover, serum CgA was not an accurate marker to identify or exclude the rare neuroendocrine differentiation of breast cancer. We therefore conclude that CgA is not useful as a serum marker in breast cancer.

Proteomics: A panel of seven serum biomarkers as a promising diagnostic tool for breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22019-e22019
Author(s):  
R. Lastra ◽  
A. Monasterio ◽  
I. Alvarez-Busto ◽  
J. Mayordomo ◽  
J. Algorta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Serum Proteins ◽  
Simultaneous Detection ◽  
Serum Biomarkers ◽  
Protein Chip ◽  
Differentially Expressed ◽  
Clinical Validation ◽  
Serum Samples ◽  
Screening Programs ◽  
Healthy Women

e22019 Background: Conventionals serum biomarkets have a low sensibility in breast cancer diagnosis. Proteomic is a promising tool to identify new proteins profiles to be used in screening and early diagnosed. Methods: 1)Biomarker identification: Serum proteins from 114 women were separated and analysed by bidimensional gel electrophoresis; data from 72 patients (p) were compared with those from 42 control women to search for differentially expressed proteins. Several comparisons were performed between controls and p regarding clinical parameters such as histological type, tumour stage and lymph node affection (-/+). A total of 53 spots were found to be differentially expressed and identified by mass spectrometry (MS) as potential breast cancer biomarkers.2) Protein Chip development: A Protein Chip was developed with antibodies against six biomarkers and three control proteins (an antibody for the detection of a spiked control, for data normalization and two proteins as positive and negative controls). An antibody against CA15–3 antigen was also included as a reference breast tumour marker to be compared with our biomarker panel. 3) Clinical validation of the Protein Chip: A clinical validation study was carried out with 75 healthy women and 125 breast cancer p. After multivariate statistical analysis of the biomarker data, CA15–3 was discarded due to its low significance while a panel of 5 biomarkers was obtained as the best predictive model to discriminate p from healthy subjects. Results: 53 diferentially expressed proteins have been identified as potential breast cancer serum biomarkers after analysing 114 serum samples by 2DE Technology. A Protein Chip has been developed for the simultaneous detection of five serum biomarkers and three control proteins. After clinical validation with 200 p and healthy women, the sensitivity of the Protein Chip to detect breast cancer was 95% and its specificity was 27%. Conclusions: The high sensitivity of the Protein Chip suggests that it could be a valid tool to complement mammography (sensitivity < 80%) in breast cancer screening programs, specially when its sensitivity tends to decrease, as it happens in young women and dense breast cases. Larger clinical validation trials are being developed. This work is supported by INDAS BIOTECH. No significant financial relationships to disclose.

Serum HER2 in the context of circulating tumor cells in patients with metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10599-10599 ◽  
Author(s):  
Volkmar Mueller ◽  
Sabine Riethdorf ◽  
Brigitte Kathrin Rack ◽  
Wolfgang Janni ◽  
Peter A. Fasching ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Elevated Serum ◽  
Metastatic Breast ◽  
Serum Levels ◽  
Her2 Status ◽  
Cellsearch System ◽  
Prognostic Information

10599 Background: Circulating tumor cells (CTC) reflect an aggressive tumor behavior by hematogenous tumor cell dissemination. Overexpression of HER2 in breast cancer (BC) is associated with increased angiogenesis and therefore potentially linked to increased hematogenous tumor cell spread. The aim of the analysis was to investigate whether concentrations of serum HER2 (sHER2) deliver prognostic information in the context of CTC detection in metastatic BC patients. Methods: Blood was obtained in a prospective multicenter setting from 254 patients with metastatic BC at the time of disease progression. sHER2 was determined using a commercial ELISA-kit (Wilex). CTC were detected with the CellSearch system (Veridex). Patients received systemic treatment according to national and international guidelines including HER2-targeted treatment. Results: Five or more CTC were detected in 122 of 245 evaluable patients (49.8%).119 of 251 (47%) metastatic patients had serum sHER2 levels above 15ng/mL. Median PFS was 9.2 months (95%-CI: 9.9 – 13.0 mths) with elevated sHER2 versus 11.4 mths (9.9 – 13.0 mths) with non-elevated levels (p=0.07). OS was 17.4 mths (14.6 – 20.3 mths) vs. 26.5 mths (23.1-29.8 mths; p<0.01). In patients with 5 or more CTC, serum levels were above the cut-off for sHER2 in 61% vs. 33% in those with less than 5 CTC (p< 0.01). Patients with elevated sHER and 5 or more CTC hat a PFS of 9.1 mths (7.2 – 11.1 mths) and a OS of 14.5 mths (11.8 – 17.2 mths), those with non-elevated sHER2 and less than 5 CTC a PFS of 12.1 (10.1 – 14.1 mths) and a OS of 29.5 month (25.4 – 33.6 mths) (p=0.15 for PFS and p< 0.01 for OS). Including sHER2, CTC and established prognostic factors in the multivariate analysis, the presence of CTC, line of therapy, ER and HER2 status of the primary tumor remained independent predictors of OS. Conclusions: Elevated serum levels of sHER2 are associated with the presence of CTC and indicate poor clinical outcome. However, sHER2 has no independent prognostic value when presence of CTC were taken into account.

Circulating exosomal microRNAs as novel detection biomarkers in pancreatic cancer

2020 ◽  
Author(s):  
Lun Wu(Former Corresponding Author) ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Ying Wei ◽  
Hong-Mei Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Rna Isolation ◽  
Serum Levels ◽  
Tumor Stage ◽  
Serum Samples ◽  
Expression Levels ◽  
Transmission Electron ◽  
Significant Difference ◽  
Novel Biomarkers ◽  
Exosomal Mirna

Abstract Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantified using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P<0.001). However, no significant difference in the relative serum levels of free miR-21 and miR-210 was observed between these two groups (both P>0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.

scholarly journals Prognostic Value of RANKL/OPG Serum Levels and Disseminated Tumor Cells in Nonmetastatic Breast Cancer

2018 ◽  
Vol 25 (4) ◽  
pp. 1369-1378 ◽  
Author(s):  
Tilman D. Rachner ◽  
Sabine Kasimir-Bauer ◽  
Andy Göbel ◽  
Kati Erdmann ◽  
Oliver Hoffmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Prognostic Value ◽  
Disseminated Tumor Cells ◽  
Serum Levels
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