scholarly journals Micro RNA-21 expression levels in invasive breast carcinoma with a non-invasive component

2015 ◽  
Vol 67 (4) ◽  
pp. 1285-1295 ◽  
Author(s):  
Nina Petrovic ◽  
Snezana Jovanovic-Cupic ◽  
Goran Brajuskovic ◽  
Silvana Lukic ◽  
Jelena Roganovic ◽  
...  

Invasive ductal carcinomas with a non-invasive component (IDC-DCIS) are classified as a group of invasive breast carcinomas, together with pure invasive ductal carcinomas of the breast (IDC). MicroRNA-21 (miR-21) has been characterized as a factor of breast cancer invasiveness, however the difference in miR-21 expression levels between IDC-DCIS and pure IDC tumors and the correlations with standard diagnostic and prognostic parameters inside the IDC-DCIS group are unknown. Our aim was to determine if miR-21 had the ability to distinguish these two invasive breast cancer groups. Levels of miR-21 expression were measured by a stem-loop quantitative Real-Time PCR (RT-qPCR) method. Expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and proliferative index Ki-67 were evaluated by immunohistochemistry. IDC-DCIS tumors had significantly lower levels of miR-21 expression in grade 2 (P=0.003, Mann-Whitney U test), ER positive (P=0.025, Mann-Whitney U test) and PR positive tumors (P=0.024, Mann-Whitney U test) than pure IDCs. miR-21 levels showed a different pattern of expression in IDC-DCIS compared to IDC tumors, which is based on the difference in miR-21 expression between Her-2 negative and Her-2 positive IDC-DCIS tumors (P=0.030, Mann-Whitney U test) and high negative correlation of miR-21 levels with PR levels (?=-0.886, P=0.006, Spearman correlation). According to our results, IDC-DCIS breast carcinomas act in a different manner in pure IDC tumors with regard to the relations between miR-21 expression levels and the standard diagnostic and prognostic parameters, such as Her-2 status, ER and PR status and protein levels.

2014 ◽  
Vol 31 (3) ◽  
Author(s):  
Nina Petrović ◽  
Vesna Mandušić ◽  
Boban Stanojević ◽  
Silvana Lukić ◽  
Lidija Todorović ◽  
...  

2005 ◽  
Vol 23 (11) ◽  
pp. 2477-2492 ◽  
Author(s):  
Mitch Dowsett ◽  
Steve R. Ebbs ◽  
J. Michael Dixon ◽  
Anthony Skene ◽  
Clive Griffith ◽  
...  

Purpose To investigate the relationships between biomarker changes in breast cancer during neoadjuvant (preoperative) endocrine therapy. Patients and Methods The IMPACT trial compared the preoperative use of tamoxifen with anastrozole alone or in combination in postmenopausal women (n = 330) with primary breast cancer. Biomarkers were measured in tumor biopsy specimens taken at baseline, and after 2 and 12 weeks of treatment. Results A decrease in the proliferation marker Ki67 occurred in the majority of patients: 52 (93%) of 56, 46 (85%) of 54, and 37 (84%) of 44 patients in the anastrozole, tamoxifen, and combination groups, respectively. There was a significantly greater suppression of Ki67 in the anastrozole-treated group than in the tamoxifen- or combination-treated groups, which is parallel to the greater efficacy seen for anastrozole over these two treatments in the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial. A positive relationship was noted between estrogen-receptor level and Ki67 suppression in all patients. Ki67 was reduced to a greater extent in progesterone receptor-positive tumors compared with progesterone receptor-negative tumors. HER-2-negative tumors tended to show a greater reduction in Ki67 compared with HER-2-positive tumors, but the difference was only significant in the tamoxifen group after 2 weeks, and in the anastrozole group after 12 weeks. Conclusion These results confirm the value of Ki67 as a molecular marker, and provide information regarding the relationships between treatment-induced changes in Ki67 and other important biomarkers. Studies such as this should help integrate agents targeted at growth factor signaling with endocrine agents in breast cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Olfat Shaker ◽  
Ghada Ayeldeen ◽  
Amr Abdelhamid

Early-stage detection of BC is a critical factor for effective treatment of the disease and can increase the survival rate of BC patients. Long non-coding RNAs can act as miRNA decoys by sequestering miRNAs, thus acting as competing endogenous RNAs and leading to re-expression of miRNA target genes. Maternally expressed 3 (MEG3) is LncRNA and it was reported to be tumor suppressor in breast cancer. The study aims to investigate the effect of MEG3 SNP (rs7158663 G/A) and its association with breast cancer risk in the Egyptian population. In addition, demonstrate the consequence of the MEG3 polymorphism on the expression levels of MEG3, miR-182, and miRNA-29. MEG3 rs7158663 G/A was genotyped and serum MEG3, miRNA-182, and miRNA-29 were measured in 180 breast cancer, 120 FA, and 150 controls by the qPCR. Frequencies of MEG3 rs7158663 GA/AA genotype and A allele were significantly higher in BC patients compared to the controls results showed that serum MEG3 levels were significantly lower, according to the presence of the A allele in different study groups while the expression of miR-182 and miRNA 29 were significantly elevated. MEG3, miR-182, and miRNA-29 are key genes involved in the development of BC, are considered as a novel potential non-invasive diagnostic biomarker for BC.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10768-10768
Author(s):  
F. Gago ◽  
D. R. Ciocca ◽  
B. Mendiondo ◽  
J. Orozco ◽  
O. Tello

10768 Clinical and pathological characteristics of basal -like breast carcinomas. Background: Genetic studies have revealed different subtypes of breast carcinomas with particular molecular characteristics. Basal-like breast carcinomas are characterized by negative hormonal receptors and negative HER-2 receptor. We have compared basal-like breast carcinomas with a randomized control population selected from our data base of breast cancer. Methods: From 2127 breast invasive carcinomas, 716 were evaluated with immunohistochemical methods, considering the expression of estrogen receptors, progesterone receptor, HER-2 and p53 protein, between 1989 and 2005. According to the molecular classification the results were: 1) Luminal 398 (55.6%), 2) HER- 2 positive: 193 (26.9%) and 3) Basal-like 124 (17.5%). We retrospectively analyzed the age at diagnosis, menopausal status, tumor size, histological grade, histopathology, lymph node status, stage and the evolution of the breast cancer. The average follow-up was 66.2 months. The control group consisted of 170 patients. The statistical analysis was performed with chi-square test, Fisher’s test and the non parametric test of the Mac Nemar’s signs. Results: The median age at diagnosis was 52 years old. This is lower than the average age of the Tumor Register of Mendoza, that is 60 years (p: < 0.01). The basal-like carcinomas predominated in premenopausal women (p = 0.07), and had a higher proportion of high tumor grade (p ≤ 0.0001) and expression of p53 protein (p=0.01). There were not significant statistical differences concerning the tumor size, the lymph node status, histopathology, and the stage at presentation. The 5-year disease-free survival (DFS) of basal-like breast carcinomas was 71.7% and the 5-year overall survival (OS) was 83.3%. Whereas the DFS for the control group was 77.3% and the OS was 87.3%. Conclusions: The basal-like breast carcinomas are characterized by having a younger age at presentation, predominating in premenopausal women, and presenting a high tumor grade with overexpression of p53 protein. No significant financial relationships to disclose.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 543-543
Author(s):  
A. M. Gown ◽  
L. C. Goldstein ◽  
P. L. Porter ◽  
R. B. Livingston ◽  
S. Tam ◽  
...  

543 Background: Drugs that poison the mitotic spindle, including taxanes and vinca alkaloids, are active agents against breast cancer. Preliminary evidence showed that high expression levels of tau predicted improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. We now tested whether levels of tau and another microtubule associated protein, beta-tubulin, could predict PFS and OS in multivariate analysis using other prognostic marker studies, including ER, PR, p53 and Ki-67 on a tissue microarray (TMA) obtained from patients in the SWOG S0102 trial. Materials and Methods: Immunohistochemistry (IHC) using antibodies to tau, beta-tubulin, ER, PR, p53, and Ki-67 was performed on a TMA constructed from the S0102 paraffin blocks. All markers were scored semiquantitatively from 0 to 3. Progression free survival (PFS) and overall survival (OS) were evaluated using multivariate analysis. Results: A total of 38 patients (41.3%) were evaluated. Tau was positively correlated with ER (r=0.36; p=0.0325) and PR (r=0.63; p<0.0001), but not with beta tubulin (p=0.34), Ki-67 (p=0.58), or age (p=0.73). Beta tubulin was not significantly correlated with any other markers. Adjusting for age, there was a significant effect of tau expression on OS (HR=0.667, p= 0.0193) and PFS (HR=0.653; p=0.0035), with higher tau associated with longer survival. When adjusted for both age and PR, there was a marginally significant effect of tau on OS (HR=0.582; p=0.056) and PFS (HR=0.604; p= 0.065). Beta tubulin was not associated with OS (HR=0.909; p=0.66) and PFS (HR=0.904; p=0.58) adjusted for age. Conclusions: In multivariate analysis, identification of breast cancer specimens showing high expression levels of tau predicts improved PFS and OS in patients with metastatic HER-2-negative breast cancers treated with docetaxel and vinorelbine plus filgrastim. High expression of tau also correlated with PR and ER expression. These results confirm and expand earlier studies of the predictive power of tau in a multivariate analysis using a panel of IHC markers for breast cancer. No significant financial relationships to disclose.


Cancer ◽  
2002 ◽  
Vol 95 (10) ◽  
pp. 2068-2075 ◽  
Author(s):  
Louise A. Quenneville ◽  
Kelly-Anne Phillips ◽  
Hilmi Ozcelik ◽  
Robert K. Parkes ◽  
Julia A. Knight ◽  
...  

2006 ◽  
Vol 24 (23) ◽  
pp. 3735-3746 ◽  
Author(s):  
Javier A. Menendez ◽  
Inderjit Mehmi ◽  
Ruth Lupu

Purpose The decision for treating breast cancer patients with trastuzumab is based on HER-2 amplification and/or overexpression. Methods Using MCF-7 cells (Her-2 ±) engineered to overexpress heregulin (MCF-7/HRG), a ligand for the Her-2/3/4 network, we investigated whether HRG-induced transactivation of Her-2 affected breast cancer cell sensitivity to chemotherapy and whether trastuzumab trigger receptor-enhanced chemosensitivity (REC) when combined with chemotherapy without Her-2 overexpression. Results MCF-7/HRG cells were more than 10-fold resistant to the alkylating agent cisplatin (CDDP), while trastuzumab coexposure completely reversed HRG-promoted CDDP resistance. A synergistic interaction between trastuzumab in combination with CDDP (paclitaxel or vincristine) was obtained in MCF-7/HRG cells. Trastuzumab prevented activation of the antiapoptotic and proliferative cascades and inhibited HRG-induced Her-2/3 phosphorylation. CDDP efficacy was enhanced by trastuzumab in cells expressing endogenously high levels of HRG. Conversely, trastuzumab coexposure was ineffective in enhancing chemotherapy efficacy in cells that did not secrete HRG, such as MCF-7 cells overexpressing a structural mutated HRG isoform. Therefore, trastuzumab-induced REC, in the absence of Her-2 overexpression, occurs through the kinase activity of Her-2/3. Interestingly, HRG expression in tumor biopsies from invasive breast carcinomas (n = 189) revealed that, whereas the minority (12%) of Her-2 positive tumors (n = 60; 32%) demonstrated Her-2 phosphorylation, the majority (67%) of HRG-overexpressing and Her-2 tumors (n = 57; 30%) were in active Her-2 status. Conclusion We demonstrate that assessment of HRG expression and Her-2 activation define a particular breast cancer patient population for which trastuzumab plus CDDP or taxol are extremely efficient without Her-2 overexpression.


Author(s):  
Arun Ajay ◽  
Priya Radhakrishnan

Background: Worldwide breast cancer is the most frequently diagnosed life threatening cancer in women and a leading cause of cancer death among women. In Kerala, India around 30% of cancer-affected women have carcinoma breast. Breast carcinomas which do not express estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2/neu) receptors are known as triple negative breast carcinomas (TNBC). They are extremely aggressive with poor prognosis. Here the authors described the clinical pathological and epidemiological characters of triple negative breast carcinomas in a tertiary care hospital in Kerala, India and compare with non-TNBC.Methods: It was a cross sectional comparative study. Clinical, pathological and epidemiological characteristics of 75 cases of TNBC were compared with that of 225 cases of non-TNBC presented in Department of General Surgery, Government medical college, Kozhikode, Kerala, India between a period from March 2014 to October 2015 (20 months). Patients were recruited after obtaining an informed consent. ER, PR, HER-2/neu status were determined by immunohistochemical staining. Data obtained were statistically analyzed using SPSS software.Results: Triple negative breast carcinoma was significantly associated with a younger age (mean age 43.67 years), early age of menarche. Commonly seen in premenopausal age group (78.7%). Patients with the triple-negative carcinoma had relatively large tumors (mean size 4.45cm compared to 3.14cm) and a high rate of node positivity (86.67%). More advanced stage at diagnosis with high grade tumor characteristics. Most common histopathology was invasive ductal carcinoma (98.7%) but no statistical difference was noted with non-TNBC.Conclusions: No significant difference was noted between TNBC and non TNBC on comparing family history, parity, age at 1st child birth, OCP use. The outcome of the disease following treatment was unable to study due to short time frame of the study.


2021 ◽  
Author(s):  
Sajjad Eslamkhah ◽  
Nazila Alizadeh ◽  
Sahar Safaei ◽  
Mohammad Amini ◽  
ahad Mokhtarzadeh ◽  
...  

Abstract Aim: Breast cancer (BC) has been classified among the main causes of death owing to females' cancer. Carboplatin is a platinum-based chemotherapeutic drug that is an important treatment option for BC. But high and frequent doses of carboplatin usually reducing the reaction of cancer cells to medication. There is an immediate need to establish methods for increasing the carboplatin susceptibility to BC cells. For instance, micro RNAs (miRNAs) such as MiR34a demonstrate significant potential. Considering that, this research was planned to explore the better clinical effect and underlying mechanism of miR-34a as a possible tumor inhibitor and drug resistance regulator in compound with carboplatin chemotherapy drug in the cell lines of BC in humans. Methods: MCF-7 cell line was transfected with miR-34a to perform functional analyses. Subsequently, the MTT assay was applied to assess cell viability. Cell viability and cell death associated gene expression amounts including Bax, Bcl-2, caspase-3, MDR1, P53, and mir34-a, were examined through real-time quantitative PCR. Results: Findings showed that miR-34a upregulation significantly decreased MCF7 cell viability in comparison with control group. Furthermore, separate treatment of cells with miR-34a mimics and carboplatin could significantly increase Bax, Caspase-3, P53, and decrease in Bcl-2 mRNA expression levels evaluated to the non-treated group. Moreover, by reduction in expression levels of the MDR1 gene, BC cells' reaction to carboplatin has increased via miR-34a. Conclusion: In line with the findings, it could be inferred that miR-34a may improve the responsiveness of breast cancer cells to carboplatin chemotherapy with downregulation of MDR1.


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