Predictive and prognostic functions of microtubule-associated protein-tau and topoisomerase IIα protein in early breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22169-e22169
Author(s):  
M. Choi ◽  
H. Won ◽  
K. Lee ◽  
S. Sung ◽  
B. Moon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Cytotoxic Agents ◽  
Breast Cancers ◽  
Topoisomerase Iiα ◽  
Poor Prognostic Factor ◽  
Node Positive ◽  
Luminal Type ◽  
Topo Ii ◽  
Prognostic Functions

e22169 Background: Topoisomerase IIα protein(topo II) is the molecular target of topo II inhibitors such as anthracyclines and Microtubule-Associated Protein(MAP)-tau protein is associated with taxane sensitivity. Anthracyclins and taxanes are major cytotoxic agents of breast cancer in the adjuvant setting. The aim of this study was to evaluate the predictive and prognostic functions of MAP-tau and topo II in early breast cancers. Methods: Representative breast tumor sections were constructed from paraffin embedded specimens from 78 node positive breast cancer patients. MAP-tau and topo II protein were assessed by immunochemistry using antibody clone 4F1(Affinity BioReagents,USA) and clone Ki-S1 antibody(Dakocytomation,USA). MAP-tau staining of tumor cells was semiquantatively scored as 0, 1+, 2+, 3+ and cases with 0 or 1+ staining intensity were considered MAP-tau negative. Topo II protein over- expression was defined as the detection of nuclear staining in more than median value of evaluated cells. Results: Thirty- four cases (43.6%) of 78 samples showed topo II overexpression and 35 cases(44.9%) showed MAP-tau overexpression in node positive breast cancers. HER2 overexpression was noted in 28 samples (35.9%) and 56 cases (71.8%) were compatible with the luminal type. In 43 patients (55.1%), anthracyclin and taxane were used as adjuvant therapy and in this group, both MAP-tau and topo II overexpression showed lower disease-free survival (DFS) than the others, but statistically not significant. In luminal type, MAP-tau overexpression was poor prognostic factor on DFS in Cox regression.(HR 5.644, 95% CI 1.14–28.07, p=0.034) Conclusions: Topo II overexpression and MAP-tau overexpression in node positive breast cancers were not significant predictive factors for anthracyclin and taxane therapies. As several investigators reported, MAP-tau is associated endocrine therapy sensitivity in patients without chemotherapy, but higher MAP-tau in luminal type was a strong poor prognostic factor in patients who were given chemotherapy and hormonal therapy. No significant financial relationships to disclose.

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.

Detection of Isolated Tumor Cells in Bone Marrow Is an Independent Prognostic Factor in Breast Cancer

2003 ◽  
Vol 21 (18) ◽  
pp. 3469-3478 ◽  
Author(s):  
G. Wiedswang ◽  
E. Borgen ◽  
R. Kåresen ◽  
G. Kvalheim ◽  
J.M. Nesland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Vascular Invasion ◽  
Independent Prognostic Factor ◽  
Histologic Grade ◽  
Separate Analysis ◽  
Node Negative ◽  
Node Positive

Purpose: This study was performed to disclose the clinical impact of isolated tumor cell (ITC) detection in bone marrow (BM) in breast cancer. Patients and Methods: BM aspirates were collected from 817 patients at primary surgery. Tumor cells in BM were detected by immunocytochemistry using anticytokeratin antibodies (AE1/AE3). Analyses of the primary tumor included histologic grading, vascular invasion, and immunohistochemical detection of c-erbB-2, cathepsin D, p53, and estrogen receptor (ER)/progesterone receptor (PgR) expression. These analyses were compared with clinical outcome. The median follow-up was 49 months. Results: ITC were detected in 13.2% of the patients. The detection rate rose with increasing tumor size (P = .011) and lymph node involvement (P < .001). Systemic relapse and death from breast cancer occurred in 31.7% and 26.9% of the BM-positive patients versus 13.7% and 10.9% of BM-negative patients, respectively (P < .001). Analyzing node-positive and node-negative patients separately, ITC positivity was associated with poor prognosis in the node-positive group and in node-negative patients not receiving adjuvant therapy (T1N0). In multivariate analysis, ITC in BM was an independent prognostic factor together with node, tumor, and ER/PgR status, histologic grade, and vascular invasion. In separate analysis of the T1N0 patients, histologic grade was independently associated with both distant disease-free survival (DDFS) and breast cancer–specific survival (BCSS), ITC detection was associated with BCSS, and vascular invasion was associated with DDFS. Conclusion: ITC in BM is an independent predictor of DDFS and BCSS. An unfavorable prognosis was observed for node-positive patients and for node-negative patients not receiving systemic therapy. A combination of several independent prognostic factors can classify subgroups of patients into excellent and high-risk prognosis groups.

p53 and bcl-2 expression correlates with clinical outcome in a series of node-positive breast cancer patients.

1996 ◽  
Vol 14 (5) ◽  
pp. 1604-1610 ◽  
Author(s):  
R Silvestrini ◽  
E Benini ◽  
S Veneroni ◽  
M G Daidone ◽  
G Tomasic ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Mitochondrial Protein ◽  
Axillary Node ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Prognostic Information ◽  
P53 Overexpression ◽  
P53 Expression ◽  
Node Positive

BACKGROUND AND PURPOSE The tumor-suppressor gene TP53 and the proto-oncogene bcl-2 encode, respectively, for a nuclear phosphoprotein and for a mitochondrial protein involved in multiple cellular functions. The proteins provide prognostic information in node-negative breast cancer and are supposed to influence treatment responsiveness. We analyzed the predictive role of p53 and bcl-2 expression, alone and in association with other variables, in postmenopausal women with node-positive, estrogen receptor-positive (ER+) breast cancers treated with radical or conservative surgery plus radiotherapy and adjuvant tamoxifen for at least 1 year. PATIENTS AND METHODS On 240 resectable cancers, we determined the expression of p53 and bcl-2, using immunohistochemistry, cell proliferation (3H-thymidine labeling index [3H-dT LI]), and ER and progesterone receptors (PgR). RESULTS p53 expression and 3H-dT LI were weakly related to one another and both were unrelated to bcl-2. Relapse-free and distant metastasis-free survival at 5 years were significantly lower for patients with tumors that highly expressed p53 (P = .0001) and for those that weakly expressed or did not express bcl-2 (P = .02). However, p53, but not bcl-2, provided prognostic information independent of tumor size, axillary node involvement, steroid receptors, and 3H-dT LI. Moreover, the simultaneous p53 overexpression and lack of PgR identified patients at maximum risk of relapse, whereas bcl-2 overexpression, associated with a low 3H-dT LI or the presence of PgR, improved the prognostic resolution for low-risk patients. CONCLUSION p53 expression appears to be indicative of clinical outcome in postmenopausal patients treated with tamoxifen. Whether p53 overexpression and weak bcl-2 expression are indicators of biologic aggressiveness, regardless of treatment, or of hormone resistance remains to be defined.

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.

scholarly journals Overexpression of ECT2 is a strong poor prognostic factor in ER(+) breast cancer

2019 ◽  
Author(s):  
Yingying Xiu ◽  
Wei Liu ◽  
Tianyi Wang ◽  
Yi Liu ◽  
Minwen Ha
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Poor Prognostic Factor

scholarly journals EMI2 expression as a poor prognostic factor in patients with breast cancer

2020 ◽  
Vol 36 (8) ◽  
pp. 640-648
Author(s):  
Anupama Vadhan ◽  
Yen‐Yun Wang ◽  
Shyng‐Shiou F. Yuan ◽  
Yi‐Chen Lee ◽  
Stephen Chu‐Sung Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Poor Prognostic Factor

Interleukin-17-producing cell infiltration in the breast cancer tumour microenvironment is a poor prognostic factor

2013 ◽  
Vol 63 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Wen-Chung Chen ◽  
Yu-Hsuan Lai ◽  
Hung-Yu Chen ◽  
How-Ran Guo ◽  
Ih-Jen Su ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factor ◽  
Tumour Microenvironment ◽  
Cell Infiltration ◽  
Interleukin 17 ◽  
Poor Prognostic Factor

scholarly journals NOTCH1 is a poor prognostic factor for breast cancer and is associated with breast cancer stem cells

2016 ◽  
Vol Volume 9 ◽  
pp. 6865-6871 ◽  
Author(s):  
Ying Zhong ◽  
Songjie Shen ◽  
Yidong Zhou ◽  
Feng Mao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Prognostic Factor ◽  
Cancer Stem Cells ◽  
Breast Cancer Stem Cells ◽  
Poor Prognostic Factor

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.

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