scholarly journals Increased PD-1 MRNA Expression in Peripheral Blood Cells of ER+ and PR+ Breast Cancer Patients and Its Unfavorable Prognostic Value

2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 207s-207s
Author(s):  
C. Liu ◽  
Y. Yu ◽  
Y. Sun ◽  
D. Guo ◽  
B. Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Prognostic Value ◽  
Metastatic Breast ◽  
Peripheral Blood Cells ◽  
Mrna Levels ◽  
Breast Cancer Patients

Background: The clinical significance of programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) expression on tumor infiltrating lymphocytes in breast cancer patients has been confirmed, while that of peripheral blood cells derived immune molecules remain unclear. Aim: We aimed to investigate the clinical importance of immune molecules, including PD-1 and CTLA-4, expression in peripheral blood cells of breast cancer patients, especially in terms of the relationship between immune molecules and estrogen receptor (ER)/progesterone receptor (PR) status, as well as their prognostic values. Methods: We enrolled 109 breast cancer patients, including 52 cases before surgery and neoadjuvant treatment (PreS group), 18 cases postsurgery and adjuvant chemoradiotherapy (PostS group), 39 metastatic cases presalvage treatment (Met group), and 21 age- and sex-matched healthy volunteers). The mRNA abundance of PD-1, CTLA-4, IL-2 receptor alpha (IL-2Rα), and cluster of differentiation 28 (CD28), forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), and interleukin-10 (IL-10) in pretreatment peripheral blood were analyzed by quantitative real-time PCR. Results: ER+ breast cancer patients showed significant higher mRNA levels of PD-1, CTLA-4, IL-2Rα, and CD28 with fold changes of 10.8, 2.4, 5.0, and 3.8, respectively ( P < 0.05) than that of ER− cases. Similarly, PR+ patients showed increased levels of PD-1, CTLA-4, and CD28 with fold changes of 6.7, 2.0, and 2.5, respectively ( P < 0.05) comparing to that of PR− cases. Patients in PreS group and Met group showed higher mRNA levels of PD-1, CTLA-4, IL-2Rα, CD28, FOXP3, TGF-β, and IL-10 than PostS group and healthy volunteers. Univariable analysis revealed that high PD-1 expression was associated with poorer progression-free survival (PFS) in metastatic breast cancer patients (5.9 vs 14.6 months, HR: 2.47, 95% CI: 1.22-5.02, P = 0.046). Meanwhile, the prognostic value of PD-1 was remained in multivariate analyses (HR: 2.22, 95% CI: 1.04-4.73, P = 0.039). Conclusion: Increased PD-1, CTLA-4, and CD28 mRNA abundance were showed in breast cancer patients and ER+/PR+ cases, which may provide the rationale for combining checkpoint inhibitors with endocrine therapy for breast cancer treatment. Furthermore, PD-1 is a promising prognostic biomarker for metastatic breast cancer.

Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy

2009 ◽  
Vol 24 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Raquel A. Nunes ◽  
Xiaochun Li ◽  
Soonmo Peter Kang ◽  
Harold Burstein ◽  
Lisa Roberts ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Treatment Response ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Her 2

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.

Detection of circulating tumor cells in peripheral blood of heavily treated metastatic breast cancer patients

Breast Cancer ◽  
2011 ◽  
Vol 18 (3) ◽  
pp. 195-202 ◽  
Author(s):  
Nahomi Tokudome ◽  
Yoshinori Ito ◽  
Shunji Takahashi ◽  
Kokoro Kobayashi ◽  
Shinichiro Taira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Breast Cancer Patients

Morphologic variation of circulating tumor cells in metastatic breast cancer patients visualized by immunofluorescent stain pattern.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
Daniel Adams ◽  
Stuart S Martin ◽  
Monica Charpentier ◽  
Olga V Makarova ◽  
Peixuan Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Peripheral Blood ◽  
Metastatic Breast ◽  
Immunofluorescent Staining ◽  
Initial Assessment ◽  
Breast Cancer Patients

e21079 Background: Isolation of circulating tumor cells (CTCs) using microfiltration is a growing utility in the field of CTC detection. The microfiltration approach can be used on peripheral blood as a non-invasive liquid biopsy for cancer detection and subtyping. We present a utilization of the CellSieve microfilter to subtype CTCs based on immunofluorescent staining pattern of cytokeratin filamentation and EpCAM surface marker expression. Our initial study on CTCs in patient blood indicates that disseminated CTC populations have high rates of phenotypic heterogeneity. Further detailed molecular analysis and patient tracking of these phenotypes may lead to individualized patient assessment based on CTC characterization. Methods: 7.5 mL of whole blood collected from metastatic breast cancer patients were diluted in a fixative solution. An 8 µm CellSieve precision microfilter was placed into a filter holder and the samples were passed through the filter (~ 90 seconds). The cells captured on the filter were fixed, permeabilized, and stained with DAPI, cytokeratin (FITC), EpCAM (PE), and CD45 (Cy5). Cells without CD45 staining were classified by their morphology, nuclear integrity and the presence of cytokeratin and EpCAM staining. Results: In our initial assessment, patient samples were found to have a number of phenotypic CTC subtypes. Cytokeratin filamentation was clearly seen on a number of CTCs while other cells presented with spotted patterns, implying CTCs in various stages of apoptosis. Later stage apoptosis, with segmented nuclear signature, was also seen in various samples. Cell clusters and cells in division were DAPI positive, while EpCAM positivity was negligible, 0-3 cells/sample, correlating with established data from the CellSearch CTC assay. Conclusions: In addition to enumeration, phenotypic variation of CTCs may be a valuable tool for the personalized care of cancer patients. We have shown that individual breast cancer patients have overlapping phenotypes of CTCs circulating in their peripheral blood. We have begun categorizing patients based on these phenotypes and plan to correlate them with overall prognosis.

Prognostic value of vitamin-D level in non-metastatic breast cancer patients in Saudi Arabia

The Breast ◽  
2019 ◽  
Vol 44 ◽  
pp. S91
Author(s):  
S. Elsamany ◽  
A. Zeeneldin ◽  
O. Elemam ◽  
S. Elmorsy ◽  
N. Abu Hashish
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Saudi Arabia ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Metastatic Breast ◽  
Breast Cancer Patients

scholarly journals Prognostic value of vitamin-D level in non-metastatic breast cancer patients in Saudi Arabia.

2020 ◽  
Vol 1 (1) ◽  
pp. 9-14
Author(s):  
Shereef Elsamany ◽  
Omaima Elemam ◽  
Ahmed Zeeneldin ◽  
Soha Elmorsy ◽  
Ahmed Khatry ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Saudi Arabia ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Metastatic Breast ◽  
Survival Outcome ◽  
Clinicopathological Factors ◽  
Breast Cancer Patients

Background Deficiency of vitamin-D (Vit-D) was associated with poor survival outcome in several studies across different tumour types. The present study aims to assess the prevalence and prognostic value of Vit-D deficiency among breast cancer patients in a single institution in Saudi Arabia. Methods In this retrospective study, we screened patients who presented with non-metastatic breast cancer to King Abdullah Medical City, Saudi Arabia from June 2011 to December 2015. We checked baseline Vit-D level before starting systemic therapy in addition to other clinicopathological factors. Low Vit-D was defined as Vit-D level less than 30 ng /ml. The relations of Vit-D level (taking the median as the cutoff) with clinicopathological factors were assessed using Chi-Square test. Differences in survival outcome were compared using log rank test. Results We screened 340 patients with non-metastatic breast cancer. Baseline Vit-D levels were available for 189 patients. The median age was 50 years (range: 26- 86 years). Noteworthy, 169 (89.4%) of patients had Vit-D level <30 ng/ml with a median of 14.9 ng/ml (range: 4.0 - 45.0). Low Vit-D level (below the median) was significantly more common in premenopausal (p=0.011) and ER-negative patients (p=0.011). However, lymphovascular invasion (p=0.001), clinically (p=0.023) and pathologically positive axillary LNs (p=0.041) were linked with higher Vit- D level. After a median follow up period of 58.2 months, 14 patients died and 40 relapsed. The 5-year disease-free survival (DFS) rates was 74.8%. The 5-year DFS rate in patients with higher Vit-D level above the median was 78.8% compared to 71.1% in patients with lower Vit-D level with no statistically significance difference (p= 0.22). The 5-year overall survival (OS) rate was 90.2%. Meanwhile, no difference in 5-year OS rate in patients with higher and lower Vit-D levels (90.3% and 89.7% respectively, p=0.6). Conclusion Low Vit-D level was prevalent among the studied breast cancer patients. Low Vit-D level was associated with ER-negative phenotype and premenopausal patients. Baseline Vit-D level was not significantly linked with survival outcome.

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