scholarly journals Tamoxifen protects breast cancer patients from COVID-19: first evidence from real world data

2021 ◽  
Author(s):  
Sara Bravaccini ◽  
Fabio Nicolini ◽  
William Balzi ◽  
Irene Azzali ◽  
Arianna Calistri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Protective Role ◽  
In Vitro Experiments ◽  
Breast Cancer Patients ◽  
Real World Data ◽  
17Β Estradiol ◽  
Hormonal Therapies

Abstract Background COVID-19 severity is uneven between genders. We hypothesized a role of hormonal therapies in the severity of COVID-19 in breast cancer (BC) patients via the modulation of SARS-CoV-2 susceptibility genes. Patients and Methods We mined the Emilia Romagna region (Italy) registries to compare the rates of hospitalization and mortality for COVID-19 in 2020 amongst 24628 BC patients. Next, we analyzed the modulation of ACE2, TMPRSS2 and NRP1 gene expression and the susceptibility to SARS-CoV-2 infection by tamoxifen, fulvestrant and 17β-estradiol on human ER+ MCF-7 cells in vitro.Results The hospitalization rate observed for 4784 tamoxifen treated BC patients was the lowest (OR, 0.41; 95% CI, 0.18-0.94; p=0.04) among hormonal therapies and no fatalities occurred. A standard mortality rate reduction has been observed also for patients treated with aromatase inhibitors (SMR: 0.73; 95% CI, 0.45-0.90). In vitro experiments showed that fulvestrant, but not tamoxifen, increases ACE2, TMPRSS2 and NRP1 gene expression and susceptibility to SARS-CoV-2 infection and that 17β-estradiol reduces significantly TMPRSS2 and NRP1 expression.Conclusions Tamoxifen treated BC patients showed a reduced rate of hospitalization and strikingly no fatalities for COVID-19. In vitro experiments confirmed a protective role of tamoxifen while an increased susceptibility to SARS-CoV-2 infection of ER+ cells treated with fulvestrant was observed.

scholarly journals Role of Metastasis in Hypertabastic Survival Analysis of Breast Cancer: Interaction with Clinical and Gene Expression Variables

2012 ◽  
Vol 5 ◽  
pp. CGM.S8821 ◽  
Author(s):  
Mohammad A. Tabatabai ◽  
Wayne M. Eby ◽  
Nadim Nimeh ◽  
Karan P. Singh
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Cancer Patients ◽  
Estrogen Receptor Status ◽  
The Other ◽  
Primary Concern ◽  
Breast Cancer Patients ◽  
Receptor Status

This paper analyzes the survival of breast cancer patients, exploring the role of a metastasis variable in combination with clinical and gene expression variables. We use the hypertabastic model in a detailed analysis of 295 breast cancer patients from the Netherlands Cancer Institute given in. 1 In comparison to Cox regression the increase in accuracy is complemented by the ability to analyze the time course of the disease progression using the explicitly described hazard and survival curves. We also demonstrate the ability to compute deciles for survival and probability of survival to a given time. Our primary concern in this article is the introduction of a variable representing the existence of metastasis and the effects on the other clinical and gene expression variables. In addition to making a quantitative assessment of the impact of metastasis on the prospects for survival, we are able to look at its interactions with the other prognostic variables. The estrogen receptor status increase in importance, while the significance of the gene expression variables used in the combined model diminishes. When considering only the subgroup of patients who experienced metastasis, the covariates in the model are only the clinical variables for estrogen receptor status and tumor grade.

scholarly journals G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis

2017 ◽  
Vol 114 (27) ◽  
pp. 7077-7082 ◽  
Author(s):  
Francesco Casciello ◽  
Fares Al-Ejeh ◽  
Greg Kelly ◽  
Donal J. Brennan ◽  
Shin Foong Ngiow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Tumor Growth ◽  
Cellular Proliferation ◽  
Gene Signature ◽  
Breast Cancer Patients ◽  
Hypoxic Response ◽  
And Migration

G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse factor in tumor growth and metastasis, the role of G9a in regulating gene expression in hypoxia has not been described extensively. Here, we show that G9a protein stability is increased in hypoxia via reduced proline hydroxylation and, hence, inefficient degradation by the proteasome. This inefficiency leads to an increase in H3K9me2 at its target promoters. Blocking the methyltransferase activity of G9a inhibited cellular proliferation and migration in vitro and tumor growth in vivo. Furthermore, an increased level of G9a is a crucial factor in mediating the hypoxic response by down-regulating the expression of specific genes, includingARNTL,CEACAM7,GATA2,HHEX,KLRG1, andOGN. This down-regulation can be rescued by a small molecule inhibitor of G9a. Based on the hypothesis that the changes in gene expression would influence patient outcomes, we have developed a prognostic G9a-suppressed gene signature that can stratify breast cancer patients. Together, our findings provide an insight into the role G9a plays as an epigenetic mediator of hypoxic response, which can be used as a diagnostic marker, and proposes G9a as a therapeutic target for solid cancers.

Immunologic markers associated with favorable prognosis in breast cancer patients: Role of innate immune system.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 43-43
Author(s):  
M. L. Ascierto ◽  
M. Kmieciak ◽  
M. O. Idowu ◽  
D. Bedognetti ◽  
A. De Maria ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Nk Cells ◽  
Nk Cell ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Favorable Prognosis ◽  
Cell Target

43 Background: Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the interacting cell. In addition to inhibitory and activating receptors, NK cells express adhesion molecules that allow conjugate formation between NK cells and their tumor targets. We have recently identified by transcriptional analysis of breast tumor specimens a signature of 5 genes, which included B cell response and interferon signaling, found to predict with > 85% accuracy relapse-free survival. In the current study we analyzed by gene expression profile, whether a differential expression of activatory and inhibitory receptors and gene involved in NK cell-target interactions could be identified in relapse and relapse free patients.Methods: RNA extraction and gene expression analysis was performed on tumor specimens with at least 10% of infiltrating cells deriving from 9 from breast cancer patients who had either 3-7 years relapse-free survival (n=9) or developed tumor relapse within 1-3 years after the initial treatment (n=8). Data were analyzed by BRB tools and Partek software.Results: Our results showed that patients with a favorable prognosis showed increased expression of genes involved in NK interaction with tumor cells and NK activating signaling. In particular an up-regulation of leukocyte function-associated antigen 1 (LFA-1) gene, typically involved in NK cells adhesion to target cells and DNAM 1, usually associated with activation of NK cells and considered one of the major protagonist of NK- Dendritic cells crosstalk, was observed to occur in relapse free patients. In addition, an up regulation of CD96 and CRTAM which, like DNAM 1, promote NK cell-target cell adhesion by interacting with the Necl2 and poliovirus receptor (PVR), was observed in relapse free patients. Conclusions: Our observation suggests that the NK signatures are associated with favorable outcome in breast cancer and allow us to generate new hypothesis on the role of innate immunity in this contest.

Polymorphisms in Cancer Susceptibility Genes XRCC1, RAD51 and TP53 and the Risk of Breast Cancer in Serbian Women

2016 ◽  
Vol 31 (3) ◽  
pp. 258-263 ◽  
Author(s):  
Ana M. Krivokuca ◽  
Milena R. Cavic ◽  
Emina J. Malisic ◽  
Jelena D. Rakobradovic ◽  
Daniela Kolarevic-Ivankovic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Hereditary Breast Cancer ◽  
Odds Ratio ◽  
Protective Role ◽  
Genotype Distribution ◽  
Breast Cancer Patients ◽  
Significant Difference ◽  
Young Breast Cancer

Background Thanks to immense improvements in technology over the past few decades, we have witnessed a major shift towards the idea that breast cancer results from a combined effect of multiple common alleles conferring low risk. This study investigates the role of 3 nonsynonymous SNPs in the DNA repair genes XRCC1 (R399Q), RAD51 (G135C) and TP53 (Arg72Pro) in breast cancer in Serbian women. Patients and Methods Cases of BRCA1/2-negative hereditary breast cancer (n = 52), sporadic breast cancer (n = 106) and age-matched cancer-free female controls (n = 104) were obtained from the Institute for Oncology and Radiology of Serbia's blood bank. Restriction fragment length polymorphism analysis was used for genotyping. Descriptive analyses included genotype and allelic frequencies; the odds ratio and 95% confidence interval were calculated as an estimate of the relative risk. Results A significant difference in QQ+RQ versus RR genotype distribution of XRCC1 was observed between hereditary breast cancer patients and cancer-free controls. The association was confirmed among young breast cancer patients from these high-risk families. The existence of 3 recessive alleles in the RAD51 and XRCC1 genotype combination showed an association with hereditary breast cancer. Odds ratio analysis indicated a strong protective role of the RAD51 GG + TP53 ArgArg + XRCC1 RR combined genotype against hereditary breast cancer negative for BRCA1/2 mutations. Conclusions The XRCC1 R399Q polymorphism showed an association with increased breast cancer risk in Serbia, especially in the hereditary form of the disease and in young breast cancer patients. Dominant alleles of RAD51, TP53 and XRCC1 combined genotypes indicated a strong protective role against hereditary breast cancer.

scholarly journals Viability of MCF7 Cells Exposed to Basolateral Secretion from CaCo2 Cells Pretreated with Fecal Waters from Breast Cancer Patients and Controls

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 308-308
Author(s):  
Jean-Marie Bard ◽  
Christine Bobin-Dubigeon ◽  
Huyen-Trang Luu ◽  
Françoise Le Vacon ◽  
Thomas Carton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Regression Model ◽  
Breast Cancer Patients ◽  
Cell Secretion ◽  
Mcf7 Cells ◽  
Cancer Disease ◽  
Caco2 Cells ◽  
Bacterial Groups

Abstract Objectives There is increasing evidence suggesting that microbiota may play a role in breast cancer disease and influence the disease severity. Several mechanisms may be involved in this relationship. Our hypothesis is that the role of microbiota in the disease may be at least partly related to its influence in gut lipid and lipoprotein metabolisms. This hypothesis was tested in an in vitro model combining MCF7 and Caco2 cells. Methods 32 women newly diagnosed for breast cancer, before any treatment and 28 apparently healthy women provided their stools from which bacterial DNA was extracted and amplified by qPCR, targeting 16S rRNA sequences specific to bacterial groups. Fecal waters (FW) were also obtained from these stools. Intestinal Caco-2 cells grown on filter inserts were incubated apically with 10% FW for 24 h. Then, MCF-7 cells were incubated with the whole basolateral medium for 24 h. The viability of these cells was estimated by MTT test. In parallel, LXR, apolipoproteins AIV and E gene expression was estimated by RT QPCR in CaCo2 cells and short chain fatty acids (SCFA) were quantified in FW. A logistic regression model was used to establish the Odds ratios (OR) for the disease of MCF7 viability and CaCo2 gene expression. The relationship between % bacterial groups, CaCo2 gene expression, SCFA and viability was established by regression models. Results Patients and controls differed by the MCF7 viability (1.05 [1.01–1.10], p = 0.04) and a tendency towards a difference was observed for apo AIV gene expression (0.63 [0.39–1.01], p = 0.055), (OR [5th-95th]). Viability was positively correlated with % Bifidobacterium sp.  (21.18 ± 7.66, p = 0.008) and negatively correlated with valerate (−2.849 ± 1.048, p = 0.009), (ß±s.d.). These correlations were maintained in a multiple regression model. Conclusions Microbiota may interact with intestine cell lipid metabolism and therefore influence cancer disease through gut cell secretion or permeability. Funding Sources Ligue Contre le cancer and private funds from Integrated Center for Oncology.

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