scholarly journals Plasticity as an Underlying Mechanism of Tumor Heterogeneity in Breast Cancer

2020 ◽  
Author(s):  
Muhammad Waqas Akbar ◽  
Murat Isbilen ◽  
Baris Kucukkaraduman ◽  
Secil Demirkol Canli ◽  
Ege Dedeoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Protocol ◽  
Breast Tumors ◽  
Underlying Mechanism ◽  
Response To Therapy ◽  
Expression Data ◽  
Primary Tumors ◽  
Loss Of Response ◽  
Molecular Subclass ◽  
Metastatic Growth

AbstractBreast cancer shows plasticity in terms of classification. Upon drug treatment and metastasis some tumors switch to another subtype leading to loss of response to therapy. In this study, we ask the question which molecular subclasses of breast cancer are more switchable upon drug therapy and metastasis. We used in silico data to classify breast cancer tumors in PAM50 molecular classes before treatment and after treatment using gene expression data. Similar analysis was performed for primary tumors and their metastatic growth. Our analysis showed that in both scenarios some breast tumors shift from one class to another. This suggests that patients who underwent chemotherapy but resulted in relapse or/and metastasis should be retyped for molecular subclass so that treatment protocol should be adopted according to those subtypes. Additionally, 20 genes were identified as biomarkers for metastasis in breast cancer.

scholarly journals The placental growth factor (PGF) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Placental Growth Factor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Epidermal Growth ◽  
The Brain

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the placental growth factor, encoded by PGF was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with increased expression of a growth factor that is chemotactic, angiogenic (5) and important for growth of blood vessels in the brain (6).

scholarly journals Tumor Microenvironment of Metastasis (TMEM) Doorways Are Restricted to the Blood Vessel Endothelium in Both Primary Breast Cancers and Their Lymph Node Metastases

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1507 ◽  
Author(s):  
Ginter ◽  
Karagiannis ◽  
Entenberg ◽  
Lin ◽  
Condeelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Tumor Microenvironment ◽  
Lymph Nodes ◽  
Lymph Node Metastases ◽  
Lymphatic Vessels ◽  
Breast Tumors ◽  
Primary Tumors ◽  
Hematogenous Dissemination ◽  
Node Metastases

Cancer cells metastasize from primary tumors to regional lymph nodes and distant sites via the lymphatic and blood vascular systems, respectively. Our prior work has demonstrated that in primary breast tumors, cancer cells utilize a three-cell complex (known as tumor microenvironment of metastasis, or TMEM) composed of a perivascular macrophage, a tumor cell expressing high levels of the actin-regulatory protein mammalian enabled (Mena), and an endothelial cell as functional “doorways” for hematogenous dissemination. Here, we studied a well-annotated case–control cohort of human invasive ductal carcinoma of the breast and metastatic lymph nodes from a separate breast cancer cohort. We demonstrate that in primary breast tumors, blood vessels are always present within tumor cell nests (TCNs) and tumor-associated stroma (TAS), while lymphatic vessels are only occasionally present in TCN and TAS. Furthermore, TMEM doorways not only exist in primary tumors as previously reported but also in lymph node metastases. In addition, we show that TMEM intravasation doorways are restricted to the blood vascular endothelium in both primary tumors and lymph node metastases, suggesting that breast cancer dissemination to distant sites from both primary tumors and metastatic foci in lymph nodes occurs hematogenously at TMEM doorways. TMEMs are very rarely detected at lymphatic vessels and do not confer clinical prognostic significance, indicating they are not participants in TMEM-associated hematogenous dissemination. These findings are consistent with recent observations that hematogenous dissemination from lymph nodes occurs via blood vessels.

scholarly journals Direct Comparison of Metastasis-Related miRNAs Expression Levels in Circulating Tumor Cells, Corresponding Plasma, and Primary Tumors of Breast Cancer Patients

2016 ◽  
Vol 62 (7) ◽  
pp. 1002-1011 ◽  
Author(s):  
Athina Markou ◽  
Martha Zavridou ◽  
Ioanna Sourvinou ◽  
George Yousef ◽  
Sofia Kounelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Breast Tumors ◽  
Breast Cancer Patients ◽  
Healthy Individuals ◽  
Primary Tumors ◽  
Expression Levels ◽  
Breast Tissues

Abstract BACKGROUND Circulating tumor cells (CTCs) and microRNAs (miRNAs) are important in liquid biopsies in which peripheral blood is used to characterize the evolution of solid tumors. We evaluated the expression levels of miR-21, miR-146a, miR-200c, and miR-210 in CTCs of breast cancer patients with verified metastasis and compared their expression levels in corresponding plasma and primary tumors. METHODS Expression levels of the miRNAs were quantified by quantitative reverse transcription PCR (RT-qPCR) in (a) 89 primary breast tumors and 30 noncancerous breast tissues and (b) CTCs and corresponding plasma of 55 patients with metastatic breast cancer and 20 healthy donors. For 30 of these patients, CTCs, corresponding plasma, and primary tumor tissues were available. RESULTS In formalin-fixed, paraffin-embedded tissues, these miRNAs were differentially expressed between primary breast tumors and noncancerous breast tissues. miR-21 (P < 0.001) and miR-146a (P = 0.001) were overexpressed, whereas miR-200c (P = 0.004) and miR-210 (P = 0.002) were underexpressed. In multivariate analysis, miR-146a overexpression was significantly [hazard ratio 2.969 (1.231–7.157), P = 0.015] associated with progression-free survival. In peripheral blood, all miRNAs studied were overexpressed in both CTC and corresponding plasma. There was a significant association between miR-21 expression levels in CTCs and plasma for 36 of 55 samples (P = 0.008). In plasma, ROC curve analysis revealed that miR-21, miR-146a, and miR-210 could discriminate patients from healthy individuals. CONCLUSIONS Metastasis-related miRNAs are overexpressed in CTCs and corresponding plasma; miR-21 expression levels highly correlate in CTCs and plasma; and miR-21, miR-146a, and miR-210 are valuable plasma biomarkers for discriminating patients from healthy individuals.

Clinical and pathologic characteristics of patients with breast cancer and a second non-breast primary tumor.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11539-e11539
Author(s):  
Gul Atalay Basaran ◽  
Aziz Yazar ◽  
Cihan Uras ◽  
Evrim Tezcanli ◽  
Devrim Cabuk ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Primary Tumor ◽  
Breast Tumor ◽  
Cancer Metastasis ◽  
Histological Grade ◽  
Breast Tumors ◽  
Second Primary ◽  
Primary Tumors ◽  
Second Primary Tumors

e11539 Background: We aimed to investigate the clinical and pathologic characteristics of patients with breast cancer (BC) who had a non-breast primary tumor and treated in our hospital. Methods: We identified BC patients with a second non-breast primary tumor retrospectively in our database. The tumors arising in a sequence by less than 2 months are accepted as synchronous malignancies. We noted clinical and pathological characteristics of breast tumors and analyzed the relapse patterns, the frequency and type of second non-breast primary tumors. Results: A total of 48 patients were identified. Median age was 59 years old. Thirty-four patients were postmenopausal, 41 tumors were IDC, 2 were DCIS only, eight were multiffocal. Two patients had metastatic BC at the time of diagnosis. Ninety-three (n: 26) % patients had breast conserving surgery, 2 had bilateral BC. Twenty-eight patients had node negative disease, 12 had node positive disease and 2 had micrometatatic nodal involvement. Fifty-four % were T1, 31% were T2 tumors. Histological grade was 3 for 14, 2 for 15 and 1 for 7 breast tumors. Forty patients had ER positive disease, 4 had ER/ PR negative disease, 2 tumors were triple negative and 6 tumors were Her-2 positive. Among non-breast second primary tumors; 29 arose after, 11 arose before the diagnosis of BC and 8 arose synchronously with BC. The most common non-breast second primary tumors were as follows: 15% lung cancer, 20% colorectal cancers, 13% ovarian cancer, 10% thyroid cancer, and 8% lymphoma/leukemia. With a median follow up of 76 months, there were 6 relapses; 4 of them were BC relapses. Among these 4 BC relapses, 3 patients had brain metastases and one patient had bone metastasis. There were 4 deaths; 2 were due to BC metastases, one was due to rectal cancer metastasis and the other was due to relapse of sarcoma. Conclusions: Most breast tumors were at early stage and were hormone sensitive. The most common second non-breast primary tumors arising after diagnosis of BC were colorectal, thyroid and lung cancers. The most common second non-breast tumor arising synchronously with BC was lung cancer and the most common second non-breast tumor arising before diagnosis of BC was lymphoma/leukemia.

scholarly journals Six homeobox 6 (SIX6) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Visual Processing ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Optic Stalk ◽  
The Central Nervous System ◽  
Epidermal Growth

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the six homeobox 6, SIX6, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at higher levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with activation of a gene important for maintenance of multipotent retinal progenitors and expressed in regions of the central nervous system involved in visual processing including the optic stalk and retina (5-8).

scholarly journals Inhibitors of cyclin-dependent kinases 4/6 for breast cancer patients with different somatic mutations of the PIK3CA gene

2020 ◽  
pp. 40-46
Author(s):  
A. F. Nasretdinov ◽  
N. I. Sultanbaeva ◽  
Sh. I. Musin ◽  
O. N. Lipatov ◽  
A. A. Izmailov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Therapy ◽  
Endocrine Therapy ◽  
Anticancer Agents ◽  
Pik3ca Mutation ◽  
Breast Tumors ◽  
Response To Therapy ◽  
Breast Cancer Patients ◽  
Adjuvant Hormone Therapy ◽  
Pik3ca Gene

Introduction. Breast cancer is the leader in cancer incidence in theRussian Federation. The tumor is considered extremely heterogeneous and the luminal subtypes of breast tumors occupy a special place, since they are considered relatively favorable in therapy and control of the disease.Drug therapy for hormone-positive cancer has undergone significant evolution and new anticancer agents have appeared in the arsenal of the oncologist and have shown promising results compared to classical therapy. The search for predictive markers of the effectiveness of new therapy has become of great importance. This marker turned out to be a mutation in the PIK3CA gene – one of the most frequent genetic disorders in breast cancer cells. According to the literature, the presence of this mutation negatively effects on endocrine therapy for breast tumors.The aim of this study was to analyze the frequency of mutations in the PIK3CA gene among patients with hormone-positive tumors, and the effectiveness of therapy with CDK4/6 inhibitors in this group of patients.Materials and methods. The material for the study of the mutation in the PIK3CA gene was tumor biopsies of 31 patients and clinical data on the response to therapy with CDK4/6 inhibitors and classical hormone therapy.Results and discussion. The results of the work showed a high incidence of the PIK3CA mutation among hormone-positive tumors (45%). The mutation resulted in a decrease in both the median time to progression after radical surgery (from 48.4 ± 7.8 months to 30.1 ± 6.0 months) in patients receiving adjuvant hormone therapy and progression-free survival in patients receiving therapy with CDK4 /6 inhibitors (4.2 months versus 9 months). This confirmed the theory that the PIK3CA mutation negatively affects the outcome of hormone therapy.Conclusions. PIK3CA is an important predictive marker in endocrine therapy for hormone-positive tumors. Its presence not only determines the relatively worse results of treatment, but can also serve as an indication for the appointment of a special series of drugs – inhibitors of this mutation.

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 The zinc finger E-box binding homeobox transcriptional repressor ZEB1 is differentially expressed in the metastases of patients with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Tumors ◽  
Differentially Expressed ◽  
Tissue Type ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Mrna Quantification ◽  
E Box ◽  
Zeb1 Expression

Metastasis is a major problem in patients with breast cancer (1). We analyzed published microarray (2) and multiplexed mRNA quantification (3) datasets to identify transcription factors whose expression changed most significantly between primary tumors in patients with breast cancer and metastatic tissues. We identified ZEB1 as differentially expressed when comparing the transcriptomes of primary tumors of the breast to the metastases they generate (2). Analysis of a separate multiplexed mRNA quantification dataset uncovered similar differential expression of ZEB1 in metastases compared to primary breast tumors (3). ZEB1 expression has been reported as important for metastases and for the epithelial to mesenchymal transition in cancer (4-9); we found in this study, however, that ZEB1 was expressed at significantly lower levels in metastases across tissue type when compared to primary breast tumors.

Sex hormones as regulators of levels of growth factors in tissues of multiple primary tumors of female reproductive organs.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23180-e23180
Author(s):  
Oleg Ivanovich Kit ◽  
Elena Mikhaylovna Frantsiyants ◽  
Tatiana Moiseenko ◽  
Marina I. Vereskunova ◽  
Meri Viktorovich Adamyan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Sex Hormones ◽  
Sex Steroids ◽  
Breast Tumors ◽  
Uterine Myoma ◽  
Primary Tumors ◽  
Multiple Primary Tumors ◽  
Multiple Primary ◽  
Positive Correlations

e23180 Background: Sex hormones are known to be able to influence the synthesis of growth factors in breast and uterine tumors; however, their relationship in multiple primary tumors is poorly studied. The purpose of the study was to analyze correlations between sex steroids and growth factors in tissues of solitary and synchronous breast cancer and uterine myoma. Methods: Levels of estrogens (E1, E2, E3), 2OHE1 and 16α-OHE1, Р4, VEGА and EGF were measured by ELISA in tissues of breast cancer (BC, n = 37), uterine myoma (n = 27) and in synchronous BC and uterine myoma (n = 36). Results: Strong positive correlations were observed in synchronous BC and uterine myoma: E3 with VEGF (r1= 83, r2= 79; p1,2< 0.05) and EGF (r1= 78, r2= 82; p1,2< 0.05), Е1 with VEGF ( r1= 81, r2= 77; p1,2< 0.05) and EGF (r1= 76, r2= 80; p1,2< 0.05), 16-OHE1 with VEGF and EGF (r1= 80, r2= 77; p1,2< 0.05 and r1= 79 r2= 80; p1,2< 0.05). We found strong negative correlations of Е3 and VEGF (r1= 80, r2= 77; p1,2< 0.05) and EGF (r1= 79 r2= 80; p1,2< 0.05), Р4 and VEGF (r1= - 81, r2= -79; p1,2< 0.05) and EGF (r1= - 77, r2= -80; p1,2< 0.05). Solitary breast tumors showed moderate positive correlations of E2 and E1 with VEGF (r1= 56, r2= 63; p1,2< 0.05) and EGF (r1= 61, r2= 65; p1,2< 0.05) and a moderate negative correlation between VEGF and EGF and Р4 (r1= - 61, r2= -59; p1,2< 0,05). A strong negative correlation of EGF with Е1 and 16-OHE1 (r1= -79, r2= -76; р1,2< 0.05) was registered in uterine myoma. Conclusions: Tissues of synchronous primary breast tumors and uterine myoma had similar correlations between levels of growth factors and sex hormones. Solitary breast tumors and uterine myoma showed correlations typical of the tumor type. Thus, expression of growth factors in multiple primary tumors, but not in solitary ones, is subject to a clearly determined regulatory role of sex steroids and their metabolites.

scholarly journals TNFSF8 (CD153 / CD30L) is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Messenger Rna ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Expression Data ◽  
Breast Cancer Patients ◽  
Complete Understanding ◽  
Primary Tumors ◽  
Trastuzumab Treatment ◽  
Epidermal Growth

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that TNFSF8, also known as CD153 and CD30 ligand (CD30L) was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab. TNFSF8 messenger RNA expression was significantly enhanced in the primary tumors of patients treated with trastuzumab. Thus, trastuzumab treatment in patients with breast cancer is associated with increased expression, in primary tumors of the breast, of a marker with broad expression in multiple human cancers of the hematopoietic system (5, 6), and with the capacity to regulate immunoglobulin class switching (7).

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