scholarly journals ALDH1 Cancer Stem Cell Marker as a Prognostic Factor in Triple-Negative Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Sonar Soni Panigoro ◽  
Dian Kurnia ◽  
Ahmad Kurnia ◽  
Samuel Johny Haryono ◽  
Zafiral Azdi Albar
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Triple Negative ◽  
Stem Cell Differentiation ◽  
Stem Cell Marker ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Poor Prognostic Factor ◽  
Aldh1 Expression

Breast cancer is the most common cancer with an increasing incidence in Asia. About 20% of all breast cancers are triple-negative breast cancers (TNBCs). BCSC is a subset of tumor cells that has stem cell-like characteristics, such as a high capacity for self-renewal and tumor initiation, which implies that BCSC may cause aggressiveness of TNBC. ALDH1 has a role in early stem cell differentiation through its function in the oxidation of retinol to retinoic acid, proposed to be a strong candidate for breast cancer stem cells. Various studies have shown that ALDH1 is one of the markers of CSC that can be used as a prognosis indicator because it can be a biological marker for poor prognostic factors in TNBC. This study assessed the prognostic survival rate with a retrospective cohort method in TNBC patients. A total of 54 of 55 patients treated at RSCM were tested for the expression of ALDH1 through an immunohistochemistry assay of breast cancer tissue using ALDH1 staining. Survival analysis was done to obtain the prognostic data of ALDH1. Positive ALDH1 expression was obtained at 38.89% in TNBC patients. One-year survival and three years of survival in TNBC patients with positive ALDH1 expression were 42.9% and 33.3%, respectively. In this study, ALDH1 can be used as a poor survival prognostic factor with HR 2.636 and p value 0.013. The conclusion of this study is that ALDH1 can be used as a poor prognostic factor in TNBC patients although it cannot be an independent prognostic factor.

scholarly journals Tribbles Homolog 3 Involved in Radiation Response of Triple Negative Breast Cancer Cells by Regulating Notch1 Activation

Cancers ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 127 ◽  
Author(s):  
Yueh-Chun Lee ◽  
Wen-Ling Wang ◽  
Wei-Chao Chang ◽  
Yu-Hao Huang ◽  
Guan-Ci Hong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Radiation Therapy ◽  
Cancer Patients ◽  
Triple Negative ◽  
Mass Spectrometry Analysis ◽  
Radiation Response ◽  
Stem Cell Population ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Poor Prognostic Factor

Breast cancer is the most common cancer for women in Taiwan and post-lumpectomy radiotherapy is one of the therapeutic strategies for this malignancy. Although the 10-year overall survival of breast cancer patients is greatly improved by radiotherapy, the locoregional recurrence is around 10% and triple negative breast cancers (TNBCs) are at a high risk for relapse. The aim of this paper is to understand the mechanisms of radioresistance in breast cancers which may facilitate the development of new treatments in sensitizing breast cancer toward radiation therapy. Tribbles homolog 3 (TRIB3) is a pseudokinase protein and known to function as a protein scaffold within cells. It has been reported that higher TRIB3 expression is a poor prognostic factor in breast cancer patients with radiotherapy. In this study, we investigate the involvement of TRIB3 in the radiation response of TNBC cells. We first found that the expression of TRIB3 and the activation of Notch1, as well as Notch1 target genes, increased in two radioresistant TNBC cells. Knockdown of TRIB3 in radioresistant MDA-MB-231 TNBC cells decreased Notch1 activation, as well as the CD24-CD44+ cancer stem cell population, and sensitized cells toward radiation treatment. The inhibitory effects of TRIB3 knockdown in self-renewal or radioresistance could be reversed by forced expression of the Notch intracellular domain. We also observed an inhibition in cell growth and accumulated cells in the G0/G1 phase in radioresistant MDA-MB-231 cells after knockdown of TRIB3. With immunoprecipitation and mass spectrometry analysis, we found that, BCL2-associated transcription factor 1 (BCLAF1), BCL2 interacting protein 1 (BNIP1), or DEAD-box helicase 5 (DDX5) were the possible TRIB3 interacting proteins and immunoprecipitation data also confirmed that these proteins interacted with TRIB3 in radioresistant MDA-MB-231 cells. In conclusion, the expression of TRIB3 in radioresistant TNBC cells participated in Notch1 activation and targeted TRIB3 expression may be a strategy to sensitize TNBC cells toward radiation therapy.

Triple negative breast cancer: An institutional review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22214-e22214
Author(s):  
M. Dioca ◽  
M. Savignano ◽  
L. Gimenez ◽  
L. Marino ◽  
C. Delfino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Menopausal Status ◽  
Stage I ◽  
Poor Prognostic Factor ◽  
Risk Of Death ◽  
Increased Risk

e22214 Background: Triple negative breast cancer (BC) is a distinct group of tumors that show common but heterogeneous morphologic, genetic, and immunophenotypic features. Despite differences in the definition and prevalence, it comprises 8% to 20% of all breast cancers and is associated with an aggressive clinical course with significant risk of either local or systemic relapse and subsequent increased risk of death on short term follow up (particularly in the first 5 years).We study the pathological characteristics and the clinical outcome of a cohort of 77 triple negative BC patients (pts) diagnosed at our Institution. Methods: Between January 1999 and September 2008, 77 (stage I to III) triple negative BC pts. were retrospectively analyzed. All pts had their receptor status, Her neu, ck-5, ck-6 and staining for EGFR by the same pathologist. Pathological parameters (Pp) analyzed were: status of axilary lymph nodes (LN), nuclear grade, histologic grade, mitotic index and vascular invasion and the use of antraciclins in the adjuvant setting. Univariate and multivariate analysis (proporcional hazard regression Cox model) for the Pp associated with relapse, and the log rank test to compare two curves of each Pp for disease free survival (DFS), and overall survival (OS) were performed. Results: The median age was 57.8 years (range 30–86 years).The median follow up time was 57.7 months (range, 4- 241). From 77 Pts. analized, 65 (84.4%) were basal-like and 43 (64.6%) of those were GH3. Stage at the time of presentation was: 16 (20,7%) stage I; 40 (51,9%) stage II; 21 (27,7%) stage III. Pre-menopausal status was 29,48% (23 pts.), and 61% (47 pts) were LN negative. Overall, relapse rate was 38.5 % (n= 30), 63 Pts (81.8%) are still alive. Median DFS was not reached. Global DFS and OS were 59% and 79% respectively, and status of LN was the only prognostic factor. LN- vs LN+ DFS (p< 00.02) and OS p (< 0.02).All others Pp analyzed were not statistically significative. Conclusions: Despite previous studies have demonstrated that triple negative is an independent marker of poor prognosis in BC as a whole, in the LN-negative, and LN-positive groups, in this basal like population only positive LN was an independent poor prognostic factor for DFS and OS. No significant financial relationships to disclose.

scholarly journals In vitro anti-cancer effect of Crataegus oxyacantha berry extract on hormone receptor positive and triple negative breast cancers via regulation of canonical Wnt signalling pathway

2021 ◽  
Author(s):  
Salini K ◽  
Niranjali Devaraj Sivasithamparam
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Signalling Pathway ◽  
Breast Cancers ◽  
Hormone Receptor Positive ◽  
Anti Cancer ◽  
Canonical Wnt

Abstract Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of Hawthorn ( Crataegus oxyacantha ) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 mg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signalling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency and cancer growth inhibition at stem cell level can be expected.

Is young age a poor prognostic factor in triple-negative breast cancer patients? Analysis of 363 patients from single institution registry.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12023-e12023
Author(s):  
Mohamed Salah Fayaz ◽  
Gerges Attia Demian ◽  
Mustafa El-Sherify ◽  
Sadeq Abuzalouf ◽  
Thomas George ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Young Age ◽  
Lymph Node Status ◽  
Poor Prognostic Factor ◽  
Free Survival

e12023 Background: Young age is a known independent poor prognostic factor for breast cancer. Few data exist about validating such prognostic factor in triple negative subtype of breast cancer. In this study, we evaluate the prognostic value of young age presentation in triple negative breast cancer (TNBC) patients who were diagnosed in Kuwait Cancer Control Center. Methods: This is a retrospective analysis of 363 patients diagnosed with TNBC between July 1999 and June 2009. Of these, 27% were diagnosed at or below the age of 40. Chi-square test was used to correlate the age with other prognostic factors. Survival measurements were estimated using Kaplan-Meier analysis. Statistical significance was calculated using the log-rank test. Results: There was no correlation between young age at presentation and other prognostic factors including grade, T stage, lymph node status, lymphovascular invasion, and Ki67 positivity. Similarly, young age was not statistically associated with poorer 5-years overall survival (78% for patients < 40 years compared to 72% for those > 40 years; p = 0.13), disease free survival (66% vs. 61%; p = 0.5) or locoregional recurrence free survival (81% vs. 83%; p = 0.7). Conclusions: Young age does not seem to negatively impact the survival of TNBC patients nor associated with poor prognostic factors in our study population. Further studies are needed to define new prognostic factors, e.g. molecular markers, in this subtype of patients rather than the conventional clinicopathologic prognostic factors.

Beyond triple-negative breast cancer and African ancestry: Tumor phenotypes among internationally diverse patient populations.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1101-1101
Author(s):  
Evelyn Mawunyo Jiagge ◽  
Aisha Jibril ◽  
George Divine ◽  
Kofi K. Gyan ◽  
Jessica Miley Bensenhaver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
African Ancestry ◽  
West African ◽  
Stem Cell Marker ◽  
Breast Cancers ◽  
East African ◽  
Increased Risk ◽  
West African Ancestry

1101 Background: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2/ neu(triple negative breast cancer {TNBC}) are higher among African American (AA) compared to White American (WA) women. Several studies show higher TNBC frequency among selected populations of African patients. The colonial-era trans-Atlantic slave trade resulted in shared West African ancestry between contemporary AA and Ghanaian (Gh) populations. The extent to which TNBC susceptibility is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers such as Androgen Receptor (AR) and mammary stem cell marker ALDH1 is unknown. Methods: We used immunohistochemistry to assess ER, PR, HER2/ neu, AR and ALDH1 among WA (n = 153); AA (n = 76); Ethiopian (Eth)/East African (n = 90) and (Gh)/West African (n = 286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. Frequency of TNBC was significantly higher for AA and Gh patients (54% and 41%, respectively) compared to WA and Eth patients (23% and 15%, respectively); p < 0.001. These associations were unchanged when limited to patients age 50 and younger (47% and 49% for AA and Gh, respectively; versus 18% and 16% for WA and Eth, respectively); p < 0.001. Frequency of ALDH1 positivity was also higher for tumors from AA and Gh patients (32% and 36%, respectively) compared to those from WA and Eth patients (23% and 17%, respectively); p = 0.007. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively (p = 0.008). Conclusions: We found a correlation between extent of African ancestry and risk of particular BC phenotypes. West African ancestry was associated with increased risk of TNBC and breast cancers that are positive for ALDH1. Future studies of hereditary TNBC susceptibility among women with African ancestry are warranted.

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