• Title, Summary, Keyword: Triple negative breast cancer

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Response of Triple Negative Breast Cancer to Neoadjuvant Chemotherapy: Correlation between Ki-67 Expression and Pathological Response

  • Elnemr, Gamal M;El-Rashidy, Ahmed H;Osman, Ahmed H;Issa, Lotfi F;Abbas, Osama A;Al-Zahrani, Abdullah S;El-Seman, Sheriff M;Mohammed, Amrallah A;Hassan, Abdelghani A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.807-813
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    • 2016
  • Triple-negative breast cancers constitute about 15% of all cases, but despite their higher response to neoadjuvant chemotherapy, the tumors are very aggressive and associated with a poor prognosis as well as a higher risk of early recurrence. This study was retrospectively performed on 101 patients with stage II and III invasive breast cancer who received 6-8 cycles of neo-adjuvant chemotherapy. Out of the total, 23 were in the triple negative breast cancer subgroup. Nuclear Ki-67 expression in both the large cohort group (n=101) and triple negative breast cancer subgroup (n=23) and its relation to the pathological response were evaluated. The purpose of the study was to identify the predictive value of nuclear protein Ki-67 expression among patients with invasive breast cancers, involving the triple negative breast cancer subgroup, treated with neoadjuvant chemotherapy in correlation to the rate of pathological complete response. The proliferation marker Ki-67 expression was highest in the triple negative breast cancer subgroup. No appreciable difference in the rate of Ki-67 expression in triple negative breast cancer subgroup using either a cutoff of 14% or 35%. Triple negative breast cancer subgroup showed lower rates of pathological complete response. Achievement of pathological complete response was significantly correlated with smaller tumor size and higher Ki-67 expression. The majority of triple negative breast cancer cases achieved pathological partial response. The study concluded that Ki-67 is a useful tool to predict chemosensitivity in the setting of neoadjuvant chemotherapy for invasive breast cancer but not for the triple negative breast cancer subgroup.

Outcomes of Triple-Negative Versus Non-Triple-Negative Breast Cancers Managed with Breast-Conserving Therapy

  • Bhatti, Abu Bakar Hafeez;Khan, Amina Iqbal;Siddiqui, Neelam;Muzaffar, Nargis;Syed, Aamir Ali;Shah, Mazhar Ali;Jamshed, Arif
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2577-2581
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    • 2014
  • Background: Triple negative breast cancer is associated with aggressive behavior and high risk of local and regional failure. Aggressive surgical intervention is considered suitable. This makes role of breast conserving therapy (BCT) debatable in these patients. The objective of this study was to compare outcome of BCT for triple negative versus non-triple negative breast cancer. Materials and Methods: Medical records of patients who underwent breast conserving therapy from 1999 to 2009 at Shaukat Khanum Cancer Hospital and had complete receptor status information were extracted. Patients were divided into triple negative breast cancer (TNBC) and non-TNBC. Patient characteristics, medical treatment modalities and adverse events were compared. Expected five year locoregional recurrence free, disease free and overall survival was calculated. The Cox proportional hazard model was used to identify independent predictors of outcome. Results: A total of 194 patients with TNBC and 443 with non-TNBC were compared. Significant difference was present for age at presentation (p<0.0001), family history (p=0.005), grade (p<0.0001) and use of hormonal therapy (p<0.0001). The number of locoregional failures, distant failures and mortalities were not significantly different. No significant difference was present in 5 year locoregional recurrence free (96% vs 92%, p=0.3), disease free (75% vs 74%, p=0.7) and overall survival (78% vs 83%, p=0.2). On multivariate analysis, tumor size, nodal involvement and hormonal treatment were independent predictors of negative events. Conclusions: Breast conserving therapy has comparable outcomes for triple negative and non-triple negative breast cancers.

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.

The Epigenetics of Triple-Negative and Basal-Like Breast Cancer: Current Knowledge

  • Temian, Daiana Cosmina;Pop, Laura Ancuta;Irimie, Alexandra Iulia;Berindan-Neagoe, Ioana
    • Journal of Breast Cancer
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    • v.21 no.3
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    • pp.233-243
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    • 2018
  • Breast cancer has the highest incidence among all malignancies diagnosed in women. Therapies have significantly improved over the years due to extensive molecular and clinical research; in a large number of cases, targeted therapies have provided better prognosis. However, one specific subtype remains elusive to targeted therapies - the triple-negative breast cancer. This immunohistochemically defined subtype is resistant to both endocrine and targeted therapies, leading to its poor prognosis. A field that is of great promise in current cancer research is epigenetics. By studying the epigenetic mechanisms underlying tumorigenesis - DNA methylation, histone modifications, and noncoding RNAs - advances in cancer treatment, diagnosis, and prevention are possible. This review aims to synthesize the epigenetic discoveries that have been made related to the triple-negative breast cancer.

Clinicopathological and Prognostic Characteristics of Triple-Negative Breast Cancer (TNBC) in Chinese Patients: A Retrospective Study

  • Li, Chun-Yan;Zhang, Sheng;Zhang, Xiao-Bei;Wang, Pei;Hou, Guo-Fang;Zhang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3779-3784
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    • 2013
  • Aims: To determine the clinical, pathological and prognostic features associated with triple-negative breast cancer (TNBC). Methods: Clinical and histologic data of 21,749 breast cancer patients who were treated at Tianjin Medical University Cancer Institute and Hospital between July 2002 and December 2011 were collected. Patients were divided into two groups: those with TNBC and those with other types of breast cancer. Patients and tumor characteristics were compared between the two groups using the Chi-square test. The prognostic results of 9,823 patients in the study population were also analyzed to determine long-term survival rates in the two groups of breast cancer patients. Results: Among the breast cancer patients treated in our hospital between 2003 and 2011, 10.4%-13.5% of them had triple-negative breast cancers. Data analyses revealed significant differences in disease onset age, family history of breast cancer, tumor size, tumor histologic grade, lymph note positivity and metastatic status between TNBC and non-TNBC patients. There were also significant differences in 5-year, 7-year and 9-year disease-free and 7-year and 9-year overall survival probability between the groups. Conclusions:TNBC are associated with younger disease onset age, larger tumor size, higher rate of axillary lymph node positivity, and higher tumor histologic grade. TNBC is also related to family history of breast cancer, increased metastatic risk and poor prognosis.

ER81-shRNA Inhibits Growth of Triple-negative Human Breast Cancer Cell Line MDA-MB-231 In Vivo and in Vitro

  • Chen, Yue;Zou, Hong;Yang, Li-Ying;Li, Yuan;Wang, Li;Hao, Yan;Yang, Ju-Lun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.5
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    • pp.2385-2392
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    • 2012
  • The lack of effective treatment targets for triple-negative breast cancers make them unfitted for endocrine or HER2 targeted therapy, and their prognosis is poor. Transcription factor ER81, a downstream gene of the HER2, is highly expressed in breast cancer lines, breast atypical hyperplasia and primary breast cancers including triple-negative examples. However, whether and how ER81 affects breast cancer carcinogenesis have remained elusive. We here assessed influence on a triple-negative cell line. ER81-shRNA was employed to silence ER81 expression in the MDA-MB-231 cell line, and MTT, colony-forming assays, and flow cytometry were used to detect cell proliferation, colony-forming capability, cell cycle distribution, and cell apoptosis in vitro. MDA-MB-231 cells stably transfected with ER81-shRNA were inoculated into nude mice, and growth inhibition of the cells was observed in vivo. We found that ER81 mRNA and protein expression in MDA-MB-231 cells was noticeably reduced by ER81-shRNA, and that cell proliferation and clonality were decreased significantly. ER81-shRNA further increased cell apoptosis and the residence time in $G_0/G_1$ phase, while delaying tumor-formation and growth rate in nude mice. It is concluded that ER81 may play an important role in the progression of breast cancer and may be a potentially valuable target for therapy, especially for triple negative breast cancer.

CpG Island Methylation Profile of Estrogen Receptor Alpha in Iranian Females with Triple Negative or Non-triple Negative Breast Cancer: New Marker of Poor Prognosis

  • Ramezani, Fatemeh;Salami, Siamak;Omrani, Mir Davood;Maleki, Davood
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.2
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    • pp.451-457
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    • 2012
  • One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of estrogen receptor (ER) gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-$2^+$ overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-$2^+$ tumors and in postmenopausal patients with $ER^-$, $PgR^-$, or $ER^-/PgR^-$ tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of the ER-alpha gene frequently occurs in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.

Triple Negative Breast Cancer

  • Cetin, Idil;Topcul, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2427-2431
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    • 2014
  • Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. This mini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.

Glut1 promotes cell proliferation, migration and invasion by regulating epidermal growth factor receptor and integrin signaling in triple-negative breast cancer cells

  • Oh, Sunhwa;Kim, Hyungjoo;Nam, KeeSoo;Shin, Incheol
    • BMB Reports
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    • v.50 no.3
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    • pp.132-137
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    • 2017
  • Elevated glucose levels in cancer cells can be attributed to increased levels of glucose transporter (GLUT) proteins. Glut1 expression is increased in human malignant cells. To investigate alternative roles of Glut1 in breast cancer, we silenced Glut1 in triple-negative breast-cancer cell lines using a short hairpin RNA (shRNA) system. Glut1 silencing was verified by Western blotting and qRT-PCR. Knockdown of Glut1 resulted in decreased cell proliferation, glucose uptake, migration, and invasion through modulation of the EGFR/MAPK signaling pathway and integrin ${\beta}1$/Src/FAK signaling pathways. These results suggest that Glut1 not only plays a role as a glucose transporter, but also acts as a regulator of signaling cascades in the tumorigenesis of breast cancer.

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.