Enhancer of zeste homologue 2 ( EZH-2) expression in breast cancer: a novel marker and potential target

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22154-e22154
Author(s):  
S. Bandyopadhyay ◽  
Z. Nahleh ◽  
R. Ali Fehmi ◽  
H. Arabi ◽  
W. Sakr ◽  
...  

e22154 Background: EZH-2 is a protein involved in cell cycle regulation; it belongs to the Polycomb group of proteins and has been suggested to be associated with aggressive breast cancer. In hormone receptor negative (HR-) breast carcinomas, novel therapeutic targets are needed. Few markers have achieved the success of Her-2/neu as targeted therapy making the search for novel treatment strategies imperative. In our study we investigate the expression of EZH2 in a cohort of hormone receptor negative breast carcinomas. Methods: We identified a consecutive cohort of 84 cases of HR- breast carcinoma in 2005–2006, from the Pathology department archives. Tumor grade, size, presence or absence of DCIS, lymph node status and Her2/neu expression were documented. The race of the patients was also noted. Immunohistochemical staining for EZH2 was performed on paraffin embedded sections. Nuclear expression of EZH2 was considered as positive and the percentage of cells staining positive was estimated. Using the Mann-Whitney U test, the expression of EZH2 was correlated with the tumor characteristics listed above. Results: The mean expression of EZH2 in HR- tumors was estimated at 74% with a median of 80% (0–90). Most of these cases (n= 61) were triple negative; 23 cases were HER-2/neu positive by established criteria. Increasing expression of EZH2 was correlated with increase in tumor size (>2 cm) and increased incidence of lymph node metastasis. No correlation was seen with tumor grade, the presence or absence of DCIS and Her2/neu expression. Race did not appear to have an impact on EZH2 expression. Conclusions: Our findings suggest that EZH2 is expressed in the majority of HR - breast cancer and is associated with aggressive breast carcinomas. EZH2 could be an important therapeutic target in this patient population. The study is ongoing to further characterize EZH2‘s role and its association with survival. No significant financial relationships to disclose.

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.


Author(s):  
Ritu Yadav

 ABSTRACT:Objective:Breast cancer comprises different biological subtypes having varied spectrum of clinical and pathological features with different prognostic and therapeutic implications. This study aimed at the identification of patients on the basis of cancer biomarkers and various clinicopathological parameters.Methods: Fresh paraffin embedded tissue block sample of three hundred fifty patients of breast carcinoma were collected during 2011-2014, from the Pathology department, Pt. B.D Sharma University of Heath Sciences Rohtak, Haryana and studied in detail to determine the correlation between hormone receptor status /cytokeratin (CK) expression along with clinicopathologicalfactors.Theimmunohistochemical assay of three hundred fifty patients of breast cancer was performed.Maximum number of patients (35%) were found in the age group of <40 years. Most of the patients were observed with the grade I (59%), tumor size 2-4.9cm (45%), <4 positive lymph node status for metastasis andinfiltrate ductal carcinoma type (93%).Triple positive and triple negative breast cancer types were studiedto identify the basal and luminal phenotypes on the basis of markers CK5, 14 and CK8/18 expression.Results:The expression of CK5 &14 was found to be significantly associated with tumor grade (P=0.001 and P=0.0001), tumor size (P= 0.001) respectively.Whereas CK8/18 expression did not reveal any significant association with tumor grade,size, lymph node status and histological type of breast carcinoma.Conclusion:In conclusion the prognostic and therapeutic value of research work would be examined and validated further on larger number of samples.Keywords: Breast carcinoma, biomarkers, clinicopathological factors, Cytokeratin, hormone receptor 


2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Mahsa Ahadi ◽  
Motahareh Heibatollahi ◽  
Sara Zahedifard

Background: Breast cancer is the most prevalent neoplasm diagnosed in Iranian women. Objectives: The current study was performed to measure the hormone receptor status and its possible connection with the patient’s age, tumor size, histological grade, and lymph node status and involvement in patients with invasive ductal breast cancer (IDBC) Methods: A total of 103 women with IDBC recently diagnosed at the Department of Pathology of Shohada-E-Tajrish Hospital were entered into this study. The mean age of the patients was 48.4 years, and 59.2% of cases were 50 years old or less. Results: Most lesions (78.6%) were more than 2 cm at their greatest dimension. Grade-II lesions were observed in a large number of patients and 59.8% of cases had lymph node involvement. Positive ER, PR, and HER-2/neu were detected in 59%, 57%, and 29% of patients, respectively. A significant correlation was found between patients’ age and histologic score, tumor dimension and both histologic score and nuclear grade, and, finally, between lymph node involvement and nuclear grade. Conclusions: According to previous studies, the evaluation of hormone receptor status in patients with breast cancer is strongly recommended. Here, by studying its possible connection with the patient’s age, tumor size, histological grade, and lymph node metastasis, we detected some biomarkers, which could be used as prognostic indices in these patients. These biomarkers could help us in the clinical management of patients with IDBC by providing the best therapeutic options.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22202-e22202
Author(s):  
L. B. Delgado ◽  
R. Fresco ◽  
G. Santander ◽  
S. Aguiar ◽  
N. Camejo ◽  
...  

e22202 Background: Few Latin-American studies and none Uruguayan study have evaluated HER-2, estrogen receptor (ER) and progesterone receptor (PR) in breast cancer (BC). The purpose of the study was to investigate the frequency of these markers and the relationship between them and with clinicopathologic features in Uruguayan BC patients (pts). Methods: We retrospectively reviewed clinical records from pts who underwent curative surgery for stage I-III invasive BC at the Oncology Units of 4 institutions in Montevideo between march 2006 and march 2008. We obtained the following data: age, TNM, ER/PR status by immunohistochemistry (IHC) and HER2 status by IHC and FISH in HER2 IHC 2+. Fisher's exact test was used to analyze the data. Results: 427 pts were included. Median age was 60 years-old (range: 24–93 y), postmenopausal 75%, stages: I 33%, II 42%, III 23%, unknown 2%. ER/PR status was known in 94,6% of cases: ER+/PR+ 66,1%, ER+/PR- 11,1%, ER-/PR+ 3,5%, ER-/PR- 19,3%. HER2 status was known in 47% (199/427) of cases, being positive (IHC 3+ or FISH+) in 13.6%. Triple negative tumors were found in 32 of 199 pts (16%). HER2 was positive in 8% of pts with ER+ and/or PR+ tumors, and in 18% of pts with ER-PR- disease (p=0.08). We did not find a significant association between axillary lymph node status and HER2 status. Besides, triple negative BC did not correlate with axillary lymph node status. When analized by menopausal status, the frequency of triple negative pts was 14% in the premenopausal group and 4% in the postmenopausal group (p=0.005). In addition, the rate of triple negative BC was 0% in pts with histologic grade 1 and 10% in pts with histologic grade 2–3 (p = 0.0005). Conclusions: Our data from Uruguayan pts show a lower prevalence of HER2 positive but a similar prevalence of ER+ and PR+ operable BC than the prevalence reported in most American and European studies. In accordance with previous reports, triple negative BC correlated with younger age and higher histologic grade. No significant financial relationships to disclose.


2020 ◽  
Vol 32 (2) ◽  
pp. 14-21
Author(s):  
Sharmin Ferdousi ◽  
Shah Md Badruddoza ◽  
SM Asafuddullah

Breast Cancer incidence is increasing, but its mortality has started to decrease. The existence of strong reliable prognostic and predictive factors is of utmost importance to the practicing clinician. Some factors are only prognostic such as age, tumor size, and lymph node status, while others are both prognostic and predictive such as hormone receptors and human epidermal receptor 2 (HER’s-2) status. This study was done to see the association of HER-2 positivity with age, tumour size, grade, differentiation and lymph node deposit in breast cancer patient. A cross-sectional type of descriptive study was conducted among 50 patients. Patient age range is from 22 to 64 years (mean 42.64 ± 10.26 years). Tumour size ranged from 1 to 8 cm (mean 4.39 ± 1.564cm). Well differentiated tumour was 20, moderately differentiated tumour was 18 cases and poorly differentiated was 12 cases. HER-2/neu negative included 35(70%) cases and positive included 15(30%) cases. In this study it was found that the association between age groups and tumour differentiation with HER-2/neu status was statistically significant (p= <0.05). TAJ 2019; 32(2): 14-21


Author(s):  
Sanaz Rismanchi ◽  
Pejman Mortazavi ◽  
Samad Muhammadnejad

Background: In the last two decades, canine mammary cancer has played an essential role in human breast cancer research. There are various similarities between biological and clinical features of canine breast cancer and female breast cancer in many cases. Clinical studies and evaluation of prognostic factors in canine mammary cancer can increase reliability in generalizing results to human cancers. This study was performed in the direction of comparative oncology. Methods: We collected clinicopathological data of an invasive type of canine mammary carcinoma from clinical records and pathology reports. Age, tumor laterality, tumor size, lymph node status, and tumor grade were recorded, and the relationships between the parameters were evaluated using linear regression analysis. Results: Ninety-seven patients were included in the study, and the mean age was 10.06 ± 2.73 years. The left mammary gland was involved in 51% of cases, and pT2 was the most common tumor size. Lymph nodes were involved in 27% of patients, and 43% of tumors were grade I. Statistical analysis showed no relationship between tumor size and laterality with other clinicopathological features. However, there was a statistically significant relationship between tumor size and tumor grade, and lymph node status. As the tumor size increased, tumor grade and the risk of lymph node involvement raised. Conclusion: Similar results of this study to breast cancer in women show that canine mammary carcinoma is a suitable model in comparative oncology research. Dogs live shorter than humans so that researchers can get the results of treatment and perform survival rate assessments faster in clinical trials. By considering ethical principles, dogs with breast cancer may replace phases I and II of human clinical trials in some cancer types soon.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12050-e12050
Author(s):  
Sagar D. Sardesai ◽  
Mahmoud Kassem ◽  
Evan Morgan ◽  
Marilly Palettas ◽  
Julie Stephens ◽  
...  

e12050 Background: The clinical heterogeneity seen in HER 2 positive breast cancer (BC), mostly related to hormone receptor (HR) expression has been suggested to underlie the variability of response not only to endocrine treatments, but also to anti-HER-2 therapies. Herein, we describe our single institution experience with clinical outcomes by HR expression in early HER 2 positive BC. Methods: An IRB-approved single-institution retrospective analysis was performed for 400 consecutive patients with non-metastatic HER 2 + BC treated at the Ohio State University Comprehensive Cancer Center from 2005-2015. Medical records were reviewed for clinic-pathologic, treatment, and survival information. Disease Free Survival (DFS) was defined as time from diagnosis to first recurrence (loco-regional or distant recurrence) including second primary BC or death. Overall survival (OS) was defined as time from diagnosis to death or last known follow up. OS and DFS estimates were generated using Kaplan Meier methods and compared using Log-rank tests. Cox proportional hazard models were used to calculate univariate and multivariate hazard ratios for OS and DFS. Results: a total of 180/400(45%) patients were diagnosed with HR positive disease. The mean age was 54.1y and patients were predominately white (267, 84%), post-menopausal (190, 60%) and presented with invasive ductal cancer (293, 92%). HR negative disease was significantly associated with high tumor grade (72% vs. 52%, p <0.0001) and lower BMI (27.6 vs 30.1, p 0.0218) compared to HR + tumors. The frequency of CNS metastases was not significantly different between both groups (8 (4%) in HR + vs. 8(6%) in HR –, p 0.9909). 173(96%) of HR + patients received anti-estrogen therapy with median duration of therapy of 40.9 months and 22(13%) received adjuvant ovarian suppression. There was no significant difference between the DFS and OS by hormone receptor expression (P= 0.7459 and 0.6518 respectively). However, higher number of HR negative patients undergoing neoadjuvant therapy achieved a complete pathologic response (pCR, 64% vs 44%, p 0.0092). pCR was prognostic for both DFS(p 0.0002) and OS (p 0.0008) in HR negative subgroup and not in HR + subgroup. Conclusions: The triple positive phenotype represents a distinct clinical subtype of HER 2 positive breast cancer associated with low tumor grade and lower frequency of pCR. Consistent with other studies, pCR was not prognostic of long term survival in triple positive disease. Future trials investigating the ER/ HER 2 cross talk are needed for this patient population.


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