scholarly journals Pathways to Breast Cancer Recurrence

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Aamir Ahmad
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Recurrent Disease ◽  
Current Knowledge ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Number Of Factors ◽  
Prevention Of Breast Cancer

Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence.

scholarly journals Twist-mediated PAR1 induction is required for breast cancer progression and metastasis by inhibiting Hippo pathway

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Yifan Wang ◽  
Ruocen Liao ◽  
Xingyu Chen ◽  
Xuhua Ying ◽  
Guanping Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Invasive Breast Cancer ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Hippo Pathway ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition

Abstract Breast cancer is considered to be the most prevalent cancer in women worldwide, and metastasis is the primary cause of death. Protease-activated receptor 1 (PAR1) is a GPCR family member involved in the invasive and metastatic processes of cancer cells. However, the functions and underlying mechanisms of PAR1 in breast cancer remain unclear. In this study, we found that PAR1 is highly expressed in high invasive breast cancer cells, and predicts poor prognosis in ER-negative and high-grade breast cancer patients. Mechanistically, Twist transcriptionally induces PAR1 expression, leading to inhibition of Hippo pathway and activation of YAP/TAZ; Inhibition of PAR1 suppresses YAP/TAZ-induced epithelial-mesenchymal transition (EMT), invasion, migration, cancer stem cell (CSC)-like properties, tumor growth and metastasis of breast cancer cells in vitro and in vivo. These findings suggest that PAR1 acts as a direct transcriptionally target of Twist, can promote EMT, tumorigenicity and metastasis by controlling the Hippo pathway; this may lead to a potential therapeutic target for treating invasive breast cancer.

miR-214 inhibits epithelial–mesenchymal transition of breast cancer cells via downregulation of RNF8

2019 ◽  
Vol 51 (8) ◽  
pp. 791-798 ◽  
Author(s):  
Lu Min ◽  
Chuanyang Liu ◽  
Jingyu Kuang ◽  
Xiaomin Wu ◽  
Lingyun Zhu
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Metastasis ◽  
Breast Cancer Patients ◽  
Mesenchymal Transition ◽  
Proliferation And Invasion

Abstract MicroRNAs (miRNAs) are a class of endogenous noncoding genes that regulate gene expression at the posttranscriptional level. In recent decades, miRNAs have been reported to play important roles in tumor growth and metastasis, while some reported functions of a specific miRNA in tumorigenesis are contradictory. In this study, we reevaluated the role of miR-214, which has been reported to serve as an oncogene or anti-oncogene in breast cancer metastasis. We found that miR-214 inhibited breast cancer via targeting RNF8, a newly identified regulator that could promote epithelial–mesenchymal transition (EMT). Specifically, the survival rate of breast cancer patients was positively correlated with miR-214 levels and negatively correlated with RNF8 expression. The overexpression of miR-214 inhibited cell proliferation and invasion of breast cancer, while suppression of miR-214 by chemically modified antagomir enhanced the proliferation and invasion of breast cancer cells. Furthermore, miR-214 could modulate the EMT process via downregulating RNF8. To our knowledge, this is the first report that reveals the role of the miR-214–RNF8 axis in EMT, and our results demonstrate a novel mechanism for miR-214 acting as a tumor suppressor through the regulation of EMT.

Classifying circulating, mutation bearing tumor cells from breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 580-580
Author(s):  
William Strauss ◽  
Paul W. Dempsey ◽  
Jessamine Winer-Jones ◽  
Catherine Bingham ◽  
R. Katherine Alpaugh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Molecular Analysis ◽  
New Technologies ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Patients ◽  
Disease Heterogeneity ◽  
Mesenchymal Transition ◽  
Tissue Biopsy

580 Background: The treatment of advanced breast cancer demands systemic therapies that can address disease heterogeneity and the development of treatment resistance without a “real-time” molecular window into disease biology. New technologies have focused on increased capture and molecular analysis of circulating tumor cells (CTCs) including cells undergoing epithelial mesenchymal transition (EMT). We conducted a pilot experiment to test the efficiency of capture and cytokeratin (CK) detection and the presence of single point variants (SNV) to determine the best utility of scoring alternatives for CTC. Methods: EpCAM expressing CTC were recovered from breast cancer patients using CellSearch (Veridex) and LiquidBiopsy (Cynvenio Biosystems). EpCAM recovery and CK scoring were indexed in spiked samples and in 12 inflammatory breast cancer (IBC) patient samples using antibodies against CKs 7, 8 or CKs 1-8, 10, 13-16, 18, 19. Additionally, LiquidBiopsy template was analyzed using an Ampliseq 1.0 panel on the IonTorrent PGM. SNV present in the CTC but not white blood cell (WBC) negative controls were identified and where possible, compared to tissue biopsy SNV analyzed using Foundation One (Foundation Medicine). Results: CTCs were detected using CellSearch 10/12 (83%) (range 0-2502 CTC/7.5ml) and LiquidBiopsy 12/12 (100%) (range 6-2800 CTC/7.5mL). More CK positive events were scored using CKs 1-8, 10, 13-16, 18, 19 than CKs 7, 8 in patient samples. Upon sequencing, shared germline polymorphisms were observed in CTC and WBC. Conversely, 1 or 2 SNV were detected in the Epcam selected population but not WBC controls from 6/12 patients (frequency 1.1%-2.1% with 520-5160x coverage) with SNV observed in TP53, MPL, PIK3ca, MET and IDH1. All but one of the PIK3ca mutations were absent in evaluable tissue biopsy. Conclusions: CTC recovery and scoring are two separate events. Altered CK detection emphasized the need to tailor CTC classification to specific disease settings. Sequence analysis showed one correlated SNV among 6 evaluable comparisons to tissue reflecting variable analysis as well as the biologic disparity of metastatic disease. This pilot demonstrates the feasibility of using CTC for molecular analysis.

scholarly journals Statins Use and Risk of Breast Cancer Recurrence and Death: A Systematic Review and Meta-Analysis of Observational Studies

2016 ◽  
Vol 19 (1) ◽  
pp. 72 ◽  
Author(s):  
Marjan Mansourian ◽  
Shaghayegh Haghjooy-Javanmard ◽  
Azadeh Eshraghi ◽  
Golnaz Vaseghi ◽  
Alireza Hayatshahi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Mortality Rate ◽  
Cohort Studies ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Reduce Mortality Rate

Purpose. Statins are widely prescribed drugs for lowering cholesterol. Some studies have suggested that statins can prevent breast cancer recurrence and reduce mortality rate. However they are not conclusive. Present systematic review and meta-analysis of published cohort studies was conducted to determine the effects of statins intake and risk of breast cancer recurrence and mortality rate. Methods. Online databases (PubMed, Embase, Scopus, EBSCO and Cochrane Collaboration) were searched through October 2014. Pooled relative risks and 95 % confidence intervals were calculated with random-effects. Results. A total of 8 cohort studies (4 for recurrence 2 for mortality and 2 for both) involving 124669 participants with breast cancer were eligible. Our results suggest a significant reduction in  recurrence (OR= 0.79. I2= 38%) and death (OR = 0.84, I2 = 8.58 %) among statin users. Conclusion. Our meta-analysis suggests that breast cancer patients will benefit from statin intake, however from these cohorts we are unable to differentiate between various statins in terms of effectiveness and duration of use. We highly propose conducting randomized clinical trials. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Impact of PIK3CA tumor mutation on the association of aspirin or NSAID use and time to breast cancer recurrence.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1521-1521 ◽  
Author(s):  
Anne Marie McCarthy ◽  
Wei He ◽  
Susan Regan ◽  
Andrew T. Chan ◽  
Beverly Moy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Pik3ca Mutation ◽  
Cancer Recurrence ◽  
Primary Diagnosis ◽  
Breast Cancer Recurrence ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer ◽  
N Use ◽  
Tumor Genotyping

1521 Background: Aspirin or NSAID (A/N) use post diagnosis is associated with lower risk of breast cancer recurrence and mortality in cohort studies. A potential mechanism is that A/Ns may suppress cell growth and induce apoptosis in tumors driven by phosphatidylinositol 3 kinase ( PIK3CA), the most common oncogene mutation in breast cancer. An interaction of A/Ns and PIK3CA mutation has been observed for colorectal cancer prognosis, but has not been studied in breast cancer. The objective was to assess time to breast cancer recurrence (TTR) with respect to A/N use and PIK3CAmutation. Methods: Patients with HR+/HER2- breast cancer treated at Massachusetts General Hospital in 2009-2014 who received tumor genotyping were included. PIK3CA mutations, including 8 common hotspot mutations, were assessed by a high-throughput tumor genotyping assay using DNA from formalin-fixed, paraffin-embedded tumor tissue. A/N use beginning 6 months post diagnosis through metastasis was extracted from electronic medical records using coded data and natural language processing. Patients with de novo metastatic disease or progressive disease within 6 months of primary diagnosis were excluded. TTR was estimated using Cox proportional hazards models. Results: Among breast cancer patients (N=212), 60 (28%) used A/Ns and 69 (33%) had PIK3CA mutation (see Table). After adjusting for age, stage, adjuvant endocrine therapy, radiation, and chemotherapy, A/N users had significantly longer TTR (HR=0.65 p=0.01). The association was similar for wild type (HR=0.58 p=0.01) and PIK3CA mutated tumors (HR=0.60 p=0.06), with no significant interaction of A/N use and PIK3CA (p=0.34). Conclusions: Among HR+ breast cancer patients, those who used A/Ns following primary diagnosis had longer TTR than non-users, regardless of tumor PIK3CA mutation status. The study provides a model for how tumor genomics could be integrated into secondary chemoprevention studies. [Table: see text]

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