• Title, Summary, Keyword: TNBC

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Ultrasonographic Features of Triple-Negative Breast Cancer: a Comparison with Other Breast Cancer Subtypes

  • Yang, Qi;Liu, Hong-Yan;Liu, Dan;Song, Yan-Qiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3229-3232
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    • 2015
  • Background: Triple-negative breast cancer (TNBC) is known to be associated with aggressive biologic features and a poor clinical outcome. Therefore, early detection of TNBC without missed diagnosis is a requirement to improve prognosis. Preoperative ultrasound features of TNBC may potentially assist in early diagnosis as characteristics of disease. Purpose: To retrospectively evaluate the sonographic features of TNBC compared to ER (+) cancers which include HER(-) and HER2 (+), and HER2 (+) cancers which are ER (-). Materials and Methods: From June 2012 through June 2014, sonographic features of 321 surgically confirmed ER (+) cancers (n=214), HER2 (+) cancers (n=66), and TNBC (n=41) were retrospectively reviewed by two ultrasound specialists in consensus. The preoperative ultrasound and clinicopathological features were compared between the three subtypes. In addition, all cases were analyzed using morphologic criteria of the ACR BI-RADS lexicon. Results: Ultrasonographically, TNBC presented as microlobulated nodules without microcalcification (p=0.034). A lower incidence of ductal carcinoma in situ (p<0.001), invasive tumor size that is>2 cm (p=0.011) and BI-RADS category 4 (p<0.001) were significantly associated with TNBC. With regard to morphologic features of 41 TNBC cases, ultrasonographically were most likely to be masses with irregular (70.7%) microlobulated shape (48.8%), be circumscribed (17.1%) or have indistinct margins (17.1%) and parallel orientation (68.9%). Especially TNBC microlobulated mass margins were more more frequent than with ER (+) (2.0%) and HER2 (+) (4.8%) cancers. Conclusions: TNBC have specific characteristic in sonograms. Ultrasonography may be useful to avoid missed diagnosis and false-negative cases of TNBC.

Recent Progress in Triple Negative Breast Cancer Research

  • Mouh, Fatima Zahra;El Mzibri, Mohammed;Slaoui, Meriem;Amrani, Mariam
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.4
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    • pp.1595-1608
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    • 2016
  • Triple-negative breast cancer (TNBC) is defined as a type of breast carcinoma that is negative for expression of oestrogene and progesterone hormone receptors (ER, PR) and HER2. This form of breast cancer is marked by its aggressiveness, low survival rate and lack of specific therapies. Recently, important molecular characteristics of TNBC have been highlighted and led to the identification of some biomarkers that could be used in diagnosis, as therapeutic targets or to assess the prognosis. In this review, we summarize recent progress in TNBC research focusing on the genetic and epigenetic alterations of TNBC and the potential use of these biomarkers in the targeted therapy for better management of TNBC.

Increased Hypermethylation of Glutathione S-Transferase P1, DNA-Binding Protein Inhibitor, Death Associated Protein Kinase and Paired Box Protein-5 Genes in Triple-Negative Breast Cancer Saudi Females

  • Hafez, Mohamed M.;Al-Shabanah, Othman A.;Al-Rejaie, Salim S.;Al-Harbi, Naif O.;Hassan, Zeinab K.;Alsheikh, Abdulmalik;Theyab, Abdurrahman I. Al;Aldelemy, Meshan L.;Sayed-Ahmed, Mohamed M.
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.541-549
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    • 2015
  • Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

Elevated Serum Haptoglobin is Associated with Clinical Outcome in Triple-Negative Breast Cancer Patients

  • Tabassum, Umaira;Reddy, Obula;Mukherjee, Geetashree
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4541-4544
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    • 2012
  • Background: Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC) disease is diagnosed more frequently in younger women, and is associated with a poor prognosis. Elevated levels of serum haptoglobin protein (Hp) are observed in many malignant diseases including breast cancer. We evaluated the expression and prognostic value of Hp among patients with TNBC. Materials and Methods: Serum Hp levels were determined by Elisa in 41 patients with TNBC and 10 normal individuals. Hp status was correlated with other clinico-pathological parameters including patient survival. Results: Of the 41 patients with TNBC, Hp over expression was detected in 24 (59%) by Elisa. Hp up-regulation was confirmed by Elisa based quantification in the serum of 41 TNBC patients against lower grades and 10 normal individuals. Survival analysis revealed that Hp ($p=2.016{\times}10^{-5}$), stage ($p=2.166{\times}10^{-5}$), distant metastasis ($p=2.217{\times}10^{-5}$), tumor size ($p=1.053{\times}10^{-5}$), and tumor grade (p=0.001), correlated with patient survival on univariate analysis. Multivariate analysis revealed that Hp (p=0.001), and grade of the disease (p=0.008) were independent predictors of survival. Conclusion: Our results indicate that serum levels of Hp may play a role as a potential serum biomarker and prognostic indicator among TNBC patients. Thus, Hp may present a new promising prognostic biomarker in TNBC patients, but independent validations are now necessary for confirmation.

Low Expression of Tyrosine-protein Phosphatase Nonreceptor Type 12 is Associated with Lymph Node Metastasis and Poor Prognosis in Operable Triple-negative Breast Cancer

  • Wu, Min-Qing;Hu, Pan;Gao, Jie;Wei, Wei-Dong;Xiao, Xiang-Sheng;Tang, Hai-Lin;Li, Xing;Ge, Qi-Dong;Jia, Wei-Hua;Liu, Ren-Bin;Xie, Xiao-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.287-292
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    • 2013
  • Background: Low tyrosine-protein phosphatase nonreceptor type 12 (PTPN12) expression may be associated with breast cancer growth, proliferation, and metastasis. However, the prognostic value of PTPN12 in breast cancer has not been clearly identified. Patients and Methods: 51 triple-negative breast cancer (TNBC) patients and 83 non-TNBC patients with a histopathology diagnosis from October 2001 to September 2006 were included in this study. Immunohistochemical staining for PTPN12 on tissue microarrays was conducted. Results: High PTPN12 expression was seen in 39.2% of TNBC and 60.2 % of non-TNBC cases. Low PTPN12 expression was associated with lymph node status (p = 0.002) and distant metastatic relapse (p = 0.002) in TNBC patients. Similarly, low PTPN12 expression in non-TNBC patients was significantly correlated with lymph node status (p = 0.002), stage (p = 0.002) and distant metastatic relapse (p = 0.039). The high PTPN12 expression group was associated with longer DFS and OS compared with low PTPN12 expression group only in TNBC cases (p = 0.005, p = 0.015), according to univariate Cox regression analysis. Conclusion: These findings provide evidence that low expression of PTPN12 is associated with worse prognosis and may be used as a potential prognostic biomarker in TNBC patients.

Triple Negative Breast Cancer in People of North East India: Critical Insights Gained at a Regional Cancer Centre

  • Sharma, Mousumi;Sharma, Jagannath Dev;Sarma, Anupam;Ahmed, Shiraj;Kataki, Amal Chandra;Saxena, Rahul;Sharma, Dilutpal
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4507-4511
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    • 2014
  • Background: Breast cancer is a heterogeneous disease comprising of distinct biological subtypes with many targeted prognostic biomarkers having therapeutic implications. However, no specific targeted therapy for triple negative breast cancer has been discovered to date and hence further research is needed. Aim: The aim and objectives of the present study were to examine the prevalence of triple negative breast cancer (TNBC) in North-East India and to compare the clinicopathological parameters in two study groups defined by immunohistochemistry (IHC) - "TNBC" and "Others". Materials and Methods: We carried out a retrospective study in a cohort of 972 patients diagnosed with invasive breast carcinoma in the Department of Pathology, Dr. B. Borooah Cancer Institute, a Regional Cancer Centre for treatment and research, Guwahati, for a period of 3 years and 10 months from January 2010 to October 2013. Based on IHC findings, patients were divided into two groups - "TNBC" and "Others". All relevant clinicopathological parameters were compared in both. TNBC were defined as those that were estrogen receptor (ER), progesterone receptor (PR), and HER2/neu negative while those positive for any of these markers were defined as "Others". Results: In this study, out of total 972 cases 31.9% (310 cases) were defined as TNBC and 662 cases (68.1%) as "Others" based on IHC markers. Compared to the "Others" category, TNBC presented at an early age (mean 40 years), were associated with high grade large tumours and high rate of node positivity, IDC NOS being the most common histological subtype in TNBC. Conclusions: TNBC accounts for a significant portion of breast cancers in this part of India and commonly present at younger age and tend to be large high grade tumours.

Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells

  • Shin, Miyoung;Yang, Eun Gyeong;Song, Hyun Kyu;Jeon, Hyesung
    • BMB Reports
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    • v.48 no.6
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    • pp.342-347
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    • 2015
  • The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. [BMB Reports 2015; 48(6): 342-347]

Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

  • El-Mageed, Amal Abd El-Hafez Abd;Shawky Mohamed, Abd El-Aty;Elesawy, Basem Hasan
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.2
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    • pp.1037-1041
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    • 2013
  • Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non- triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non- triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non- triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases.

MicroRNA-301b promotes cell proliferation and apoptosis resistance in triple-negative breast cancer by targeting CYLD

  • Song, Hongming;Li, Dengfeng;Wu, Tianqi;Xie, Dan;Hua, Kaiyao;Hu, Jiashu;Deng, Xiaochong;Ji, Changle;Deng, Yijun;Fang, Lin
    • BMB Reports
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    • v.51 no.11
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    • pp.602-607
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    • 2018
  • Aberrant expression of microRNAs (miRNAs) plays important roles in carcinogenesis and tumor progression. However, the expression and biological role of miR-301b in triple-negative breast cancer (TNBC) remains unclear. Here we aimed to evaluate the roles and mechanisms of miR-301b in TNBC cells. miR-301b expression was assessed in TNBC specimens and cell lines by quantitative Real-Time PCR (qRT-PCR). TNBC cells were transfected with miR-301b mimics, inhibitors or Cylindromatosis (CYLD) small interfering RNA (siRNA) using Lipofectamine 2000. The functional roles of miR-301b were determined by cell proliferation, colony formation, and apoptosis assays. Western blots and qRT-PCR were used to measure the expression of mRNAs and proteins in the cells. We found that miR-301b was upregulated in TNBC specimens and cell lines. Overexpression of miR-301b promoted cell proliferation in TNBC cells, while inhibited the apoptosis induced by 5-FU. CYLD was downregulated by miR-301b at both mRNA and protein levels in TNBC cells. Dual-luciferase report assay confirmed that miR-301b downregulated CYLD by direct interaction with the 3'-untranslated region(3'-UTR) of CYLD mRNA. $NF-{\kappa}B$ activation was mechanistically associated with miR-301b-mediated downregulation of CYLD. However, inhibition of miR-301b reversed all the effects of miR-301b. In conclusion, miR-301b plays an oncogenic role in TNBC possibly by downregulating CYLD and subsequently activating $NF-{\kappa}B$ p65, and this may provide a novel therapeutic approach for TNBC.

Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

  • Maharjan, Sony;Park, Byoung Kwon;Lee, Su In;Lim, Yoonho;Lee, Keunwook;Kwon, Hyung-Joo
    • Biomolecules & Therapeutics
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    • v.26 no.3
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    • pp.322-327
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    • 2018
  • A type of breast cancer with a defect in three molecular markers such as the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor is called triple-negative breast cancer (TNBC). Many patients with TNBC have a lower survival rate than patients with other types due to a poor prognosis. In this study, we confirmed the anti-cancer effect of a natural compound, Gomisin G, in TNBC cancer cells. Treatment with Gomisin G suppressed the viability of two TNBC cell lines, MDA-MB-231 and MDA-MB-468 but not non-TNBC cell lines such as MCF-7, T47D, and ZR75-1. To investigate the molecular mechanism of this activity, we examined the signal transduction pathways after treatment with Gomisin G in MDA-MB-231 cells. Gomisin G did not induce apoptosis but drastically inhibited AKT phosphorylation and reduced the amount of retinoblastoma tumor suppressor protein (Rb) and phosphorylated Rb. Gomisin G induced in a proteasome-dependent manner a decrease in Cyclin D1. Consequently, Gomisin G causes cell cycle arrest in the G1 phase. In contrast, there was no significant change in T47D cells except for a mild decrease in AKT phosphorylation. These results show that Gomisin G has an anti-cancer activity by suppressing proliferation rather than inducing apoptosis in TNBC cells. Our study suggests that Gomisin G could be used as a therapeutic agent in the treatment of TNBC patients.