scholarly journals P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jonathan D. Marotti ◽  
Kristen E. Muller ◽  
Laura J. Tafe ◽  
Eugene Demidenko ◽  
Todd W. Miller
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Tumors ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Solid Organ ◽  
Breast Cancers ◽  
Primary Tumors ◽  
Receptor Status ◽  
Cancer Subtypes

Background. Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 1 (P-Rex1) has been implicated in cancer growth, metastasis, and response to phosphatidylinositol 3-kinase (PI3K) inhibitor therapy. The aim of this study was to determine whether P-Rex1 expression differs between primary and metastatic human breast tumors and between breast cancer subtypes. Design. P-Rex1 expression was measured in 133 specimens by immunohistochemistry: 40 and 42 primary breast tumors from patients who did versus did not develop metastasis, respectively, and 51 breast-derived tumors from metastatic sites (36 of which had matching primary tumors available for analysis). Results. Primary breast tumors showed significant differences in P-Rex1 expression based on receptor subtype. ER+ and HER2+ primary tumors showed higher P-Rex1 expression than primary triple-negative tumors. HER2+ metastases from all sites showed significantly higher P-Rex1 expression compared to other metastatic receptor subtypes. Solid organ (i.e., brain, lung, and liver) metastases showed higher P-Rex1 expression compared to bone metastases. Conclusions. P-Rex1 expression is increased in ER+ and HER2+ breast cancers compared to triple-negative tumors. P-Rex1 may be differentially expressed in metastatic tumors based on site and receptor status. The role of P-Rex1 in the development of breast cancer metastases and as a predictive biomarker of therapeutic response warrants further investigation.

scholarly journals Cis-Compound Mutations are Prevalent in Triple Negative Breast Cancer and Can Drive Tumor Progression

2016 ◽  
Author(s):  
Nao Hiranuma ◽  
Jie Liu ◽  
Chaozhong Song ◽  
Jacob Goldsmith ◽  
Michael Dorschner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
The Cancer Genome Atlas ◽  
Breast Cancers ◽  
Single Nucleotide Variants ◽  
Primary Tumors ◽  
Cancer Subtypes ◽  
Multiple Biopsies ◽  
Cancer Genome Atlas

About 16% of breast cancers fall into a clinically aggressive category designated triple negative (TNBC) due to a lack of ERBB2, estrogen receptor and progesterone receptor expression1-3. The mutational spectrum of TNBC has been characterized as part of The Cancer Genome Atlas (TCGA)4; however, snapshots of primary tumors cannot reveal the mechanisms by which TNBCs progress and spread. To address this limitation we initiated the Intensive Trial of OMics in Cancer (ITOMIC)-001, in which patients with metastatic TNBC undergo multiple biopsies over space and time5. Whole exome sequencing (WES) of 67 samples from 11 patients identified 426 genes containing multiple distinct single nucleotide variants (SNVs) within the same sample, instances we term Multiple SNVs affecting the Same Gene and Sample (MSSGS). We find that >90% of MSSGS result from cis-compound mutations (in which both SNVs affect the same allele), that MSSGS comprised of SNVs affecting adjacent nucleotides arise from single mutational events, and that most other MSSGS result from the sequential acquisition of SNVs. Some MSSGS drive cancer progression, as exemplified by a TNBC driven by FGFR2(S252W;Y375C). MSSGS are more prevalent in TNBC than other breast cancer subtypes and occur at higher-than-expected frequencies across TNBC samples within TCGA. MSSGS may denote genes that play as yet unrecognized roles in cancer progression.

scholarly journals Breast Cancer Pathology, Receptor Status, and Patterns of Metastasis in a Rural Appalachian Population

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Linda Vona-Davis ◽  
David P. Rose ◽  
Vijaya Gadiyaram ◽  
Barbara Ducatman ◽  
Gerald Hobbs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Lymph Node Involvement ◽  
Receptor Subtypes ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Visceral Metastasis ◽  
Receptor Status ◽  
Clinical Records

Breast cancer patients in rural Appalachia have a high prevalence of obesity and poverty, together with more triple-negative phenotypes. We reviewed clinical records for tumor receptor status and time to distant metastasis. Body mass index, tumor size, grade, nodal status, and receptor status were related to metastatic patterns. For 687 patients, 13.8% developed metastases to bone (n=42) or visceral sites (n=53). Metastases to viscera occurred within five years, a latent period which was shorter than that for bone (P=0.042). More women with visceral metastasis presented with grade 3 tumors compared with the bone and nonmetastatic groups (P=0.0002). There were 135/574 women (23.5%) with triple-negative breast cancer, who presented with lymph node involvement and visceral metastases (68.2% versus 24.3%;P=0.033). Triple-negative tumors that metastasized to visceral sites were larger (P=0.007). Developing a visceral metastasis within 10 years was higher among women with triple-negative tumors. Across all breast cancer receptor subtypes, the probability of remaining distant metastasis-free was greater for brain and liver than for lung. The excess risk of metastatic spread to visceral organs in triple-negative breast cancers, even in the absence of positive nodes, was combined with the burden of larger and more advanced tumors.

scholarly journals A Machine Learning Approach to Differentiate Two Specific Breast Cancer Subtypes Using Androgen Receptor Pathway Genes

2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Taobo Hu ◽  
Guiyang Zhao ◽  
Yiqiang Liu ◽  
Mengping Long
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Histological Subtypes ◽  
Metaplastic Breast Cancer ◽  
Cancer Subtypes ◽  
Machine Learning Approach

Triple-negative breast cancer is a heterogeneous disease with different molecular and histological subtypes. The Androgen receptor is expressed in a portion of triple-negative breast cancer cases and the activation of the androgen receptor pathway is thought to be a molecular subtyping signature as well as a therapeutic target for triple-negative breast cancer. Thus, identification of the androgen receptor pathway status is important for both molecular characterization andclinical management. In this study, we investigate the expression of the androgen receptor pathway in metaplastic breast cancer and luminal androgen receptor subtypes of triple-negative breast cancer and found that the androgen receptor pathway was downregulated in metaplastic breast cancer compared to luminal androgen receptor subtype. Using random forest, we found that the two subtypes of breast cancer can be molecularly classified with the gene expression of the androgen receptor pathway.

scholarly journals Blood Genome-Wide Transcriptional Profiles of HER2 Negative Breast Cancers Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ovidiu Balacescu ◽  
Loredana Balacescu ◽  
Oana Virtic ◽  
Simona Visan ◽  
Claudia Gherman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Transcriptional Analysis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Cancer Subtypes ◽  
Her2 Breast Cancer ◽  
Adaptive Immune Cells

Tumors act systemically to sustain cancer progression, affecting the physiological processes in the host and triggering responses in the blood circulating cells. In this study, we explored blood transcriptional patterns of patients with two subtypes of HER2 negative breast cancers, with different prognosis and therapeutic outcome. Peripheral blood samples from seven healthy female donors and 29 women with breast cancer including 14 triple-negative breast cancers and 15 hormone-dependent breast cancers were evaluated by microarray. We also evaluated the stroma in primary tumors. Transcriptional analysis revealed distinct molecular signatures in the blood of HER2− breast cancer patients according to ER/PR status. Our data showed the implication of immune signaling in both breast cancer subtypes with an enrichment of these processes in the blood of TNBC patients. We observed a significant alteration of “chemokine signaling,” “IL-8 signaling,” and “communication between innate and adaptive immune cells” pathways in the blood of TNBC patients correlated with an increased inflammation and necrosis in their primary tumors. Overall, our data indicate that the presence of triple-negative breast cancer is associated with an enrichment of altered systemic immune-related pathways, suggesting that immunotherapy could possibly be synergistic to the chemotherapy, to improve the clinical outcome of these patients.

scholarly journals Epigenetic Regulation of Immunotherapy Response in Triple-Negative Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4139
Author(s):  
Pere Llinàs-Arias ◽  
Sandra Íñiguez-Muñoz ◽  
Kelly McCann ◽  
Leonie Voorwerk ◽  
Javier I. J. Orozco ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immune Escape ◽  
Checkpoint Inhibitors ◽  
Early Stage ◽  
Regulatory Elements ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Cancer Subtypes

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptor and progesterone receptor and human epidermal growth factor receptor 2 (HER2) overexpression. This malignancy, representing 15–20% of breast cancers, is a clinical challenge due to the lack of targeted treatments, higher intrinsic aggressiveness, and worse outcomes than other breast cancer subtypes. Immune checkpoint inhibitors have shown promising efficacy for early-stage and advanced TNBC, but this seems limited to a subgroup of patients. Understanding the underlying mechanisms that determine immunotherapy efficiency is essential to identifying which TNBC patients will respond to immunotherapy-based treatments and help to develop new therapeutic strategies. Emerging evidence supports that epigenetic alterations, including aberrant chromatin architecture conformation and the modulation of gene regulatory elements, are critical mechanisms for immune escape. These alterations are particularly interesting since they can be reverted through the inhibition of epigenetic regulators. For that reason, several recent studies suggest that the combination of epigenetic drugs and immunotherapeutic agents can boost anticancer immune responses. In this review, we focused on the contribution of epigenetics to the crosstalk between immune and cancer cells, its relevance on immunotherapy response in TNBC, and the potential benefits of combined treatments.

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

Breast cancer in systemic lupus erythematosus (SLE): receptor status and treatment

Lupus ◽  
2017 ◽  
Vol 27 (1) ◽  
pp. 120-123 ◽  
Author(s):  
K Chan ◽  
A E Clarke ◽  
R Ramsey-Goldman ◽  
W Foulkes ◽  
B Tessier Cloutier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Lupus Erythematosus ◽  
General Population ◽  
Lupus Erythematosus ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Breast Cancers ◽  
Systemic Lupus ◽  
Receptor Status

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

scholarly journals Breast Cancer Recurrence Survival Among Iranian Patients; A 17-Year Retrospective Cohort Study

2021 ◽  
pp. 284-290
Author(s):  
Amirreza Ehsani ◽  
Nahid Nafissi ◽  
Mohammadamin Joulani
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Triple Negative ◽  
Cancer Recurrence ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Luminal A ◽  
Local Bone

Background: Nowadays breast cancer (BC) is the most common cancer in women. More than 1.5 million cases are detected yearly. Survival of patients is dependent on several factors. Metastasis and cancer recurrence of different types and in different locations have various outcome.  Methods: This is a retrospective cohort study to describe survival of patients after diagnosis of breast cancer based on receptor subtypes and sites of metastasis among Iranian population. A total number of 2051 females with breast cancer were evaluated and among these, 138 patients with recurrent BC were investigated. Results: The 1-year survival of local, bone, visceral and brain metastasis were 64.99%, 63%, 32.83%, and 21.57%, respectively. Based on sites of metastasis, bone and local metastasis showed the best survival while brain and visceral metastasis had the worst survival and prognosis. Conclusion: Our study showed that Her2 enriched positive BCs had the worst survival and triple negative receptor BC showed the best survival. This may be due to the discovery of Herceptin drugs for Her 2 enriched receptor breast cancers which ameliorates their prognosis and survival. Also, drugs related to luminal A and B which are used to improve their survival and hormonal therapy could be associated with their better prognosis in comparison to triple negative receptor subtype. Since our patients have not consumed Herceptin drugs over the last 17 years, the difference between our findings and those of other studies could be related to the release of this category of drugs.

scholarly journals A Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Breast Cancer Carcinogenesis and Abnormal Immunity

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1842 ◽  
Author(s):  
Jürgen Geisler ◽  
Joel Touma ◽  
Afsar Rahbar ◽  
Cecilia Söderberg-Nauclér ◽  
Katja Vetvik
Keyword(s):  
Breast Cancer ◽  
Human Cytomegalovirus ◽  
Triple Negative ◽  
Breast Tumors ◽  
Active Role ◽  
Gene Products ◽  
Breast Cancers ◽  
Wide Range

Previously recognized classical human onco-viruses can regulate complex neoplastic events, and are estimated to play a role during carcinogenesis in 15–20% of cancer cases. Although the DNA and gene products of several viruses have been found in breast tumors, none of the classical onco-viruses have definitely been linked to the initiation of breast cancer. However, recent evidence shows that human cytomegalovirus (HCMV) gene products are found in >90% of tumors and metastases of breast cancers, and their increased expression can be correlated to a more aggressive breast cancer phenotype. Supporting the active role of HCMV in breast cancer, a specific HCMV strain, HCMV-DB, was recently shown to exert oncogenic transformational activity in breast epithelial cells in vitro, and to give rise to fast-growing, triple-negative breast tumors when injected into immune deficient mice. The same observation holds true for clinical studies implying increased HCMV protein expression in triple negative breast cancer biopsies. In addition to functionally being able to hijack tumor-promoting cellular events, HCMV is known to exhibit a wide range of immunosuppressive effects, which can have radical impact on the tumor microenvironment. HCMV infected cells can avoid recognition and elimination by the immune system by orchestrating polarization of immunosuppressive type II macrophages, preventing antigen presentation, by expressing T cell inhibitory molecules, and possibly, by the induction of regulatory T (Treg) cell responses. These actions would be especially deleterious for the antigenic activation and proliferation of tumor specific CD8+ cytotoxic T lymphocytes (CTLs), whose effector functions have recently been targeted by successful, experimental immunotherapy protocols. The recognition of alternative causes and drivers of breast cancer is a pivotal research topic for the development of diagnostics and novel, effective preventive and therapeutic strategies targeting both tumor cells and their microenvironments.

scholarly journals Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Andrew A. Davis ◽  
Virginia G. Kaklamani
Keyword(s):  
Breast Cancer ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Growth Factor ◽  
Triple Negative ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
New Paradigm ◽  
Cancer Subtypes ◽  
The Metabolic Syndrome

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC.

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