scholarly journals Tamoxifen induces hypercoagulation and alterations in ERα and ERβ dependent on breast cancer sub-phenotype ex vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
K. Pather ◽  
T. N. Augustine
Keyword(s):  
Breast Cancer ◽  
Oestrogen Receptor ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Blood Platelet ◽  
T47d Cell ◽  
Receptor Expression ◽  
Activation Markers ◽  
Blood Constituents ◽  
Increased Risk

Abstract Tamoxifen shows efficacy in reducing breast cancer-related mortality but clinically, is associated with increased risk for thromboembolic events. We aimed to determine whether breast tumour sub-phenotype could predict propensity for thrombosis. We present two ex vivo Models of Tamoxifen-therapy, Model 1 in which treatment recapitulates accumulation within breast tissue, by treating MCF7 and T47D cells directly prior to exposure to blood constituents; and Model 2 in which we recreate circulating Tamoxifen by treating blood constituents prior to exposure to cancer cells. Blood constituents included whole blood, platelet-rich plasma and platelet-poor plasma. Hypercoagulation was assessed as a function of thrombin activity, expression of CD62P and CD63 activation markers defined as an index of platelet activation, and platelet morphology; while oestrogen receptor expression was assessed using immunocytochemistry with quantitative analysis. We determined, in concert with clinical studies and contrary to selected laboratory investigations, that Tamoxifen induces hypercoagulation, dependent on sub-phenotypes, with the T47D cell line capacity most enhanced. We determined a weak positive correlation between oestrogen receptor expression, and CD62P and CD63; indicating an association between tumour invasion profiles and hypercoagulation, however, other yet unknown factors may play a predictive role in defining hypercoagulation.

scholarly journals Identifying Biomarkers to Select Patients with Early Breast Cancer Suitable for Extended Adjuvant Endocrine Therapy

Breast Care ◽  
2017 ◽  
Vol 12 (3) ◽  
pp. 146-151 ◽  
Author(s):  
Ivana Sestak
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Oestrogen Receptor ◽  
Clinical Information ◽  
Late Recurrence ◽  
Correct Identification ◽  
Breast Cancer Therapy ◽  
Increased Risk ◽  
Extended Endocrine Therapy ◽  
Positive Breast Cancer

Postmenopausal women with early oestrogen receptor-positive breast cancer who have received 5 years of endocrine therapy are at increased risk of developing a recurrence. An important clinical question is how to identify women who are at highest (or lowest) risk of a recurrence. The use of prognostic biomarkers allows individualised breast cancer therapy but correct identification of patients who will benefit most from extended endocrine therapy is essential. Several multigene assays have been developed to determine the likelihood of overall recurrence but so far none exist specifically for the prediction of late recurrence. Recent results from large clinical trials have shown that biomarker assays that include clinical information in their tests might be useful to predict and risk stratify patients for late recurrence. However, further research is needed to specifically offer multigene assays for the identification of late recurrence and thus justify routine use of these tests in the clinical setting.

scholarly journals EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

Oncogene ◽  
1998 ◽  
Vol 17 (8) ◽  
pp. 1053-1059 ◽  
Author(s):  
Rina Hui ◽  
Jonathon R Ball ◽  
R Douglas Macmillan ◽  
Frances S Kenny ◽  
Owen WJ Prall ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cyclin D1 ◽  
Primary Breast Cancer ◽  
Oestrogen Receptor ◽  
Patient Survival ◽  
Receptor Expression

scholarly journals Flow Cytometric Evaluation of T Cell Activation Markers after Cardiopulmonary Bypass

2014 ◽  
Vol 2014 ◽  
pp. 1-6
Author(s):  
Maja-Theresa Dieterlen ◽  
Hartmuth B. Bittner ◽  
Attila Tarnok ◽  
Jens Garbade ◽  
Stefan Dhein ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Activation Markers ◽  
Increased Risk ◽  
Patients At Risk ◽  
Inflammatory Processes ◽  
Activation Pathways

Background. Cardiopulmonary bypass surgery (CPBS) is associated with an increased risk for infections or with subsequent organ dysfunction. As T cell activation is a central mechanism during inflammatory processes, we developed an assay to evaluate T cell activation pathways in patients undergoing CPBS.Methods. Blood was obtained from eleven patients undergoing CPBS preoperatively, on postoperative day (POD)-3, and on POD-7 and was stimulated with different concentrations of Concanavalin A (ConA). Cyclosporine and sirolimus, inhibiting different pathways of the T cell cycle, were added to blood ex vivo. Expression of T cell activation markers CD25 and CD95 was analyzed by flow cytometry.Results. In untreated blood, expression of CD25 and CD95 significantly increased with higher ConA concentrations(P<0.05)and decreased for all ConA concentrations for both antigens over the study time(P<0.05). Independently from the ConA concentration, inhibition of CD25 and CD95 expression was highest preoperatively for sirolimus and on POD-3 for cyclosporine. At all time points, inhibition of CD25 and CD95 expression was significantly higher after cyclosporine compared to sirolimus treatment(P<0.001).Conclusion. Our results showed that different pathways of T cell activation are impaired after CPBS. Such knowledge may offer the opportunity to identify patients at risk for postoperative complications.

Comparison Of The Effects Of Aspirin In Humans Ex Vivo In Platelet-Rich Plasma And Whole Blood

1981 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Trisodium Citrate ◽  
Blood Platelet ◽  
Maximal Response ◽  
Blood Samples ◽  
Platelet Concentration

The effect of aspirin on human platelet function is usually assessed using platelet-rich plasma (PRP). Some preliminary results in vitro suggested that the effect of aspirin appears to be greater in PRP than whole blood. To explore this possibility further, a comparison of the effect of aspirin in humans ex vivo has been made taking measurements simultaneously in whole blood and PRP at 2 platelet concentrations. Blood samples (36ml) were drawn from 7 male volunteers after a light breakfast. Each took 300mg soluble aspirin and blood samples were drawn again 2 hours later. Blood was mixed with 0.1 volumes 129nM trisodium citrate. Some (30ml) was then centrifuged to prepare PRP and platelet -poor plasma (PPP) by standard techniques. Platelet concentration of some PRP was adjusted with PPP to equal that of the corresponding blood sample; the rest was adjusted to 350,000 per μl. Aggregation in response to collagen (Horm, Munich) was measured photometrically at 37°. Aggregation in 0.5ml aliquots of whole blood was measured after 4 min stirring with 154mM NaCl (control) or collagen at 37° as the fall in single platelet count determined using an Ultraflo- 100 whole blood platelet counter (Clay Adams). The concentrations of collagen producing a 50% maximal response (EC50) in PRP and blood were determined. Dose-ratios for each volunteer were calculated by dividing the EC50 obtained after aspirin by the corresponding value obtained before aspirin.The effect of aspirin was significantly (p<0.001) less in blood than PRP. Whether or not the results in whole blood more closely reflect the effect of aspirin in vivo remains to be determined.

scholarly journals Circulating Low Density Neutrophils of Breast Cancer Patients are Associated with their Worse Prognosis due to the Impairment of T cell Responses

2021 ◽  
Author(s):  
Diana P. Saraiva ◽  
Bruna F. Correia ◽  
Rute Salvador ◽  
Nídia de Sousa ◽  
António Jacinto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Tumor Development ◽  
Poor Response ◽  
Response To Treatment ◽  
Low Density ◽  
Breast Cancer Patients ◽  
Activation Markers ◽  
Healthy Donors ◽  
Worse Prognosis

AbstractNeutrophils are prominent immune components of solid tumors, which can protect against the onset of cancer (N1) or have pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN, a rare subset in non-pathological conditions, have been extensively studied in cancer, due to their frequency in this disease and their pro-tumor phenotype. However, this has been mainly demonstrated in animal models and proper validation in humans is an urgent need. Here, we further enlighten the clinical impact of LDN in a cohort of breast cancer (BC) patients. We observed that LDN were practically absent in healthy donors’ blood, while were significantly increased in the blood of BC patients, particularly with metastatic disease. Relevant for a clinical translation, within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than in responders. The association of a higher incidence of circulating LDN and the worse prognosis of BC patients could be explained by the pro-tumor/immunosuppressive characteristics exhibited by these cells. Namely, there are more LDN expressing the immunosuppressive marker PD-L1, than HDN. Additionally, LDN also showed increased expression of activation markers; a robust formation of neutrophil extracellular traps; an augmented phagocytic activity; and a higher capacity to release reactive oxygen species, which may contribute for tumor development and metastization. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with the immunosuppressive CCR4+ regulatory T cells, corroborating their impairment on the anti-tumor immune responses, which was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a clinical meaningful biomarker of BC response to treatment and opens new avenues for developing targeted immunotherapies.

scholarly journals Relationship of ER, PR, HER2 / neu with Other Prognostic Factors in Breast Cancer along with the Role of Androgen Receptor in Triple Negative Breast Cancer

2021 ◽  
Vol 10 (8) ◽  
pp. 536-540
Author(s):  
Arshi Khan ◽  
Reeni Malik ◽  
Pramila Jain ◽  
Deepshikha Verma ◽  
Vedanti Newasker
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Oestrogen Receptor ◽  
Triple Negative ◽  
Receptor Expression ◽  
Proliferation Index ◽  
Lymph Node Status ◽  
Significant Information

BACKGROUND Understanding various risk factors associated with breast cancer can help in early identification & prompt treatment of patients with breast cancer. Apart from clinical parameters like age, disease presentation and menopausal status, important prognostic indicators in histopathology are size and extent of tumour, histologic type,histologic grade and lymph node status. Also, there are other factors which are not only predictive of outcome, but also direct therapies against particular molecular targets. These factors are oestrogen receptor (ER) status, progesterone receptor (PR) status, HER2 / neu status, Ki-67 proliferation index & androgen receptor (AR) status. We wanted to analyse various hormone receptors & their correlation with prognostic factors. In addition, androgen receptor expression is also studied in triple negative breast cancer cases. METHODS The study included 50 cases over a period of 18 months from January 2018 to June 2019 received in the Department of Pathology, Gandhi Medical College, Bhopal, India. These cases were subjected to histopathological & immunohistochemistry (IHC) evaluation. RESULTS Among the 50 cases studied, the most common subtype was infiltrating ductal carcinoma (NOS - no special type, 84 %). Majority of patients were ER, PR, HER2 / neu negative (48 %) and among those triple negative cases, 25 % of cases were androgen receptor positive. CONCLUSIONS Expression of the hormone receptor (ER and PR) and HER2 status may provide significant information in directing patient management. Since traditional pathological methods and IHC remain standard for guiding the use of treatment, clinicians may be challenged with equivocal results that directs towards additional testing for definitive diagnosis and, better patient outcome. The most used therapy for advanced breast cancers is based on the use of AR antagonists, such as bicalutamide and enzalutamide, first- and second-generation AR antagonists respectively. Gene signatures, bioinformatics, and other clinical trials are also beneficial for clinician in estimating the benefits expected from adjuvant chemotherapy. KEY WORDS Breast Cancer, Oestrogen Receptor, Androgen Receptor, Triple Negative

Oestrogen receptor expression in human breast cancer during long-term fulvestrant treatment

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
J. Robertson ◽  
E. Gutteridge ◽  
K. L. Cheung ◽  
S. Pinder ◽  
A. Wakeling
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Oestrogen Receptor ◽  
Receptor Expression ◽  
Human Breast

scholarly journals Clinicopathological features, survival and risk in breast cancer survivors with thyroid cancer: an analysis of the SEER database

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Shuting Li ◽  
Jiao Yang ◽  
Yanwei Shen ◽  
Xiaoai Zhao ◽  
Lingxiao Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Thyroid Cancer ◽  
Predictive Factors ◽  
Tumor Size ◽  
Clinicopathological Features ◽  
Receptor Expression ◽  
Duct Carcinoma ◽  
Increased Risk ◽  
Multiple Primary ◽  
Influent Factors

Abstract Background The co-occurrence of breast cancer (BC) and thyroid cancer (TC) has been mentioned for several years, researchers observed an increased risk of BC patients to develop TC, but few researches concern about the features, survival of BC patients followed by TC and the influent factors of the incidence risk. The present study aimed to estimate the clinicopathological features, survival of BC survivors who had primary TC and the predictive factors on the risk of BC patients to develop TC. Methods Women diagnosed with BC between 1992 and 2011, and then developed TC from the Surveillance, Epidemiology, and End Results Database were included. Standardized incidence ratios (SIRs) was used to perform multiple primary analyses, generated from the multiple primary-SIR program in SEER*Stat. Results A total of 842 BC then TC patients were included, the median age was 54 years. Additionally, 78.39% were white, 60.45% had T1 cancer, 62.47% had negative lymph nodes, and more than 75% had infiltrating duct carcinoma, 5-year survival rate was 95.4%. Compared with BC only patients, they were younger, had smaller tumor size and a relatively better prognosis. The risk of developing TC was higher in BC patients than in the general population (SIR 1.22, 95% CI [1.14, 1.31]), especially within 3 years. The influent factors of SIR were black race, BC tumor site, grade and ER/PR positive expression. Conclusions BC patients followed by TC had its particular clinicopathological features. Compared with the features and survival of BC only patients, they were younger, had a smaller tumor size and a relatively better prognosis. Furthermore, BC patients had a high risk of developing TC, especially within 3 years. Black women, primary tumor located in an upper-outer, central, or overlapping site, high grade tumor and with positive hormone receptor expression were predictive factors to develop TC.

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