scholarly journals Clinical Significance of Epigenetic Inactivation of hMLH1 and BRCA1 in Tunisian Patients with Invasive Breast Carcinoma

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Sondes Karray-Chouayekh ◽  
Fatma Trifa ◽  
Abdelmajid Khabir ◽  
Nouredine Boujelbane ◽  
Tahia Sellami-Boudawara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Gene Promoter ◽  
Disease Free Survival ◽  
Methylation Pattern ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Promoter Regions ◽  
P53 Expression ◽  
Tunisian Patients

Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1,colon cancer,nonpolyposis type 2(E. coli) and BRCA1 (breast cancer 1,early onset) in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P=.015) and 5-years disease free survival (P=.016) while hMLH1 methylation was more frequent in larger tumors (P=.002) and in presence of distant metastasis (P=.004). Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P=.006) and with overall survival (P=.015) suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer.

The value of tumor-infiltrating lymphocytes and CD8 expression as a predictor of response to anthracycline-based neoadjuvant chemotherapy in invasive breast carcinoma of no special type

2021 ◽  
pp. 1-6
Author(s):  
Upik A. Miskad ◽  
Rizki A. Rifai ◽  
Rina Masadah ◽  
Berti Nelwan ◽  
Djumadi Ahmad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune System ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Predictive Value ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Invasive Breast Carcinoma ◽  
Study Results ◽  
Infiltrating Lymphocytes

BACKGROUND: The immune system is known to play an important role in tumor cell eradication. Although cancer cells were able to escape from the immune system, many studies showed mononuclear inflammatory cell infiltrates known as tumor-infiltrating lymphocytes (TILs) on breast cancer histopathology specimens showed better prognosis, including in disease-free survival (DFS) and chemotherapy responses. OBJECTIVE: This study aimed to reveal the predictive value of tumor-infiltrating lymphocytes (TILs) levels and CD8 expression in invasive breast carcinoma of no special type patients’ samples on response to anthracycline-based neoadjuvant chemotherapy. METHODS: 75 pre-treatment biopsy samples that were diagnosed as invasive breast carcinoma of no special type were evaluated. TILs level determined following recommendations of International TILs Working Group 2014, CD8 expression assessed semiquantitatively after immunohistochemistry staining. Response to anthracycline-based neoadjuvant chemotherapy evaluated clinically using Response Evaluation Criteria in Solid Tumours (RECIST) criteria and pathologically by evaluating hematoxylin and eosin (H&E)-stained slides from mastectomy specimens after 3 or 4 cycles of neoadjuvant chemotherapy. RESULTS: Chi-squared analysis showed a significant relationship between TILs level and CD8 expression with chemotherapy responses clinically (p = 0.011 and p = 0.017 respectively) but not pathologically. Furthermore, the logistic regression test exhibit the predictive value of TILs level was 66.7% and CD8 expression was 64%. CONCLUSIONS: This study results suggest that TILs level and CD8 expression may be added as predictive factors to the response of anthracycline-based neoadjuvant chemotherapy, and oncologists may take benefit in breast cancer patient’s management.

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.

Correlation of an Estrogen Receptor-related Phosphoprotein with Histopathological Features in Breast Cancer

1989 ◽  
Vol 4 (2) ◽  
pp. 95-102
Author(s):  
R.M. Tomasino ◽  
E. Daniele ◽  
R. Nuara ◽  
V. Morello ◽  
M. Salvato ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Estrogen Receptor ◽  
Breast Carcinoma ◽  
Breast Cancers ◽  
Histopathological Features ◽  
Histological Types ◽  
Biological Meaning ◽  
Er Status

A series of 65 cases of different histological types of breast carcinoma was investigated for the immunohistochemical location of the estrogen receptor-related, 29 kD phosphoprotein using the ER-D5 monoclonal antibody. The ER-D5 response is heterogeneous in relation to some therapeutic limitations and is correlated with histopathological features of the tumors and survival. The main parameters for evaluation of breast cancers are reviewed, both those that are statistically correlated and those that are not apparently always correlated but are known to have considerable biological meaning, such as the ER-status of tumors.

Abstract Submission

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Free Survival ◽  
Increased Risk

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]

Disease-free survival pattern in breast cancer patients in India treated in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12030-e12030 ◽  
Author(s):  
Basavalinga S. Ajaikumar ◽  
Kodaganur Srinivasachar Gopinath ◽  
B S Srinath ◽  
Ramesh Bilimagga S ◽  
Nalini K Rao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Distant Failure ◽  
Her 2 ◽  
Disease Free

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.

Claudin 1, 3, 4, and 7 expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1070-1070
Author(s):  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
Jong Han Yu ◽  
jong Won Lee ◽  
Byung Ho Sohn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Endocrine Treatment ◽  
Lymph Node Status ◽  
High Recurrence Rate ◽  
Breast Cancers

1070 Background: Triple negative breast cancer (TNBC) often grows rapidly and has poor prognosis, with a high recurrence rate. Because conventional endocrine treatment and HER2 targeted therapy for TNBC is invalid, chemotherapy is the only systemic treatment for TNBC. It is known that several subtypes within the TNBC show different responses to chemotherapy, depending on the subtypes. Recently, a claudin (CLDN) low breast cancer has been identified, exhibiting low expressions of CLDNs 1, 3, 4 and 7. CLDNs are transmembrane proteins that seal tight junctions and are critical for maintaining cell-to-cell adhesion in epithelial cell sheets. However, their role in cancer progression remains largely unexplored. Methods: Surgically removed, formalin-fixed, paraffin-embedded breast cancers from 341 TNBC patients were analyzed to identify CLDN expression.They underwent wide local excision or mastectomy between March, 2004 and December, 2007 at the breast surgery unit of Asan Medical Central Hospital. Results: In our tumor series, we found 45.0% (153/339) of high expressing cases for CLDN1, 57.0% (192/337) for CLDN3, 57.6% (194/337) for CLDN4 and 44.0% (149/339) for CLDN7. Overall, we found 20.5% (70/341) of cases were within the low CLDN expression group and 79.5% (271/341) of tumors were within the high expression group of CLDN1, 3, 4 ,7. Although the high CLDN expression group was significantly associated with positive lymph node status and higher stage, there were no significant differences between CLDN low and high groups in disease free survival (p=0.477) or overall survival (p=0.253). Conclusions: CLDN high tumors are associated with poor prognosis features, but they are not an independent prognostic factor in TNBC patients. However, the mechanisms underlying the different roles of CLDNs in tumorigenesis are largely unclear. Studying the associations of these CLDNs with the TNBC subgroup of breast cancers might provide us with potential diagnostic biomarkers or therapeutic targets for cancer cells.

scholarly journals TRAIL-Induced Apoptosis in TRAIL-Resistant Breast Carcinoma Through Quercetin Cotreatment

2018 ◽  
Vol 12 ◽  
pp. 117822341774985 ◽  
Author(s):  
Jasmine M Manouchehri ◽  
Katherine A Turner ◽  
Michael Kalafatis
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Human Tumor ◽  
Breast Cancers ◽  
Treatment Regimens ◽  
Efficacious Treatment ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Mcf 7

Breast cancer is the most commonly diagnosed cancer in women. There is a continued interest for the development of more efficacious treatment regimens for breast carcinoma. Recombinant human tumor necrosis factor–related apoptosis-inducing ligand (rhTRAIL) shows potential as a potent anticancer therapeutic for the treatment of breast cancer, whereas displaying minimal toxicity to normal cells. However, the promise of rhTRAIL for the treatment of breast cancer is dismissed by the resistance to rhTRAIL-induced apoptosis exhibited by many breast cancers. Thus, a cotreatment strategy was examined by applying the natural compound quercetin (Q) as a sensitizing agent for rhTRAIL-resistant breast cancer BT-20 and MCF-7 cells. Quercetin was able to sensitize rhTRAIL-resistant breast cancers to rhTRAIL-induced apoptosis as detected by Western blotting through the proteasome-mediated degradation of c-FLIPL and through the upregulation of DR5 expression transcriptionally. Overall, these in vitro findings establish that Q is an effective sensitizing agent for rhTRAIL-resistant breast cancers.

scholarly journals Correlation between p53 Status, DNA Ploidy, Proliferation Rate and Nuclear Morphology in Breast Cancer. An Image Cytometric Study

1997 ◽  
Vol 15 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Katrin Friedrich ◽  
Volker Dimmer ◽  
Gunter Haroske ◽  
Wolfdietrich Meyer ◽  
Franz Theissig ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Cell ◽  
Dna Ploidy ◽  
Image Cytometry ◽  
Proliferation Rate ◽  
Cell Populations ◽  
Nuclear Morphology ◽  
Breast Cancers ◽  
P53 Expression ◽  
High Proliferation Rate

The study was designed to detect differences in the nuclear morphology of tumours and tumour cell populations with different p53 expression in correlation with DNA ploidy and proliferation rate. The paraffin sections from routinely processed samples of 88 breast cancers were immunostained with the monoclonal p53‐antibody DO‐1. After localization and evaluation with a scoring system the sections were destained and stained by the Feulgen method. The nuclei were relocated automatically and measured by means of the image cytometry workstation. Significant differences between the tumours and tumour cell populations with different p53 expression were found in the euploid tumours as well as in the aneuploid tumours and in the breast cancers with a high proliferation rate. The breast cancers with a low immunoreactive score (IRS 1–4) differ from the negative cancers as well as from the cancers with a higher immunoreactive score (IRS 5–12). Evaluating the nuclear populations of the p53 positive cancers, there were differences in the features of the chromatin amount and distribution in the groups of the euploid breast cancers and in cancer with a high proliferation rate. In contrast, the nuclear populations of the aneuploid cancers did not show any differences in their nuclear morphology.The results showed the different impacts of the p53 expression, DNA ploidy and the proliferation rate on the nuclear morphology in breast cancer.

scholarly journals Gene Mutations in Hereditary Breast Cancer- A Review

2020 ◽  
Vol 2 (3) ◽  
Author(s):  
Pathima Fairoosa ◽  
Chamindri Witharana
Keyword(s):  
Breast Cancer ◽  
Hereditary Breast Cancer ◽  
Cancer Susceptibility ◽  
Gene Mutations ◽  
Tumour Suppressor Genes ◽  
Breast Cancers ◽  
Germline Gene ◽  
Brca1 And Brca2 ◽  
Repair Gene ◽  
Cancer Susceptibility Genes

The most prevalent form of cancer in females is breast cancer. Roughly 5%-10% of breast cancers are hereditary, and they are associated with Germline gene mutations, inherited from parents. Germline gene mutations increase the risk of developing cancer earlier in life compared to noninherited cases (sporadic cancer). BRCA1 and BRCA2 are well-studied tumour suppressor genes associated with hereditary breast cancer. Even though mutations in BRCA1 and BRCA2 are assumed to responsible the majority of hereditary breast cancers cases, many other breast cancer susceptibility genes have been identified in the last few decades. Identification of many germline mutations was possible due to advance sequencing technologies. Most of these genes are belongs to tumour suppressors and DNA damage repair gene families (DNA double-strand break repair and DNA mismatch repair). These genes play a vital role in genomic stability and cell cycle control suggesting that any alteration in these genes trigger uncontrolled growth and tumour formation. These genes are categorized according to the penetrance level, the proportion of carriers express the associated trait of the mutated gene. Mutations in high penetrance genes such as BRCA1, BRCA2, TP53, PTEN, and SKT11 greatly increase the risk of developing breast cancer. Moderate penetrance gene such as PALB2, ATM, CHEK2, BARD1, BRIP1 and low penetrance gene such as PARP4, CASP8, TOX3 confer moderate to low increase risk of developing breast cancer. Aim of this review is to summarize genes associated with hereditary breast cancer according to their penetrance level (high, moderate and low penetrance).

scholarly journals Basal-Like Breast Cancer; Clinicopathological, Molecular, and Prognostic Features

2019 ◽  
pp. 85-91
Author(s):  
Sabrine Haddad ◽  
Ines Zemni ◽  
Irtyah Merchaoui ◽  
Ilhem Bettaib ◽  
Olfa Adouni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Poor Prognosis ◽  
Ductal Carcinoma ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Metaplastic Carcinoma ◽  
Breast Cancers ◽  
Ki 67 ◽  
Prognostic Features ◽  
The Mean

Background: Molecular classification of breast tumors has identified the basal-like subtype, with high heterogeneity and very poor prognosis. These tumors are mainly triple negative, characterized by the expression of basal markers CK5/6 and EGFR. In this study, we sought to investigate the features, outcome, and therapeutic modalities of basal-like breast cancers (BLBC).Methods: We retrospectively identified 90 BLBC patients diagnosed at the Department of Surgical Oncology of Salah Azaiez Institute between January 2009 and December 2013. Results: The mean age of our patients was 50 years, and 15.5% had a family history of breast cancer. The mean tumor size was 43.8 mm. Histological examination revealed invasive ductal carcinoma in 88.9% of the cases, metaplastic carcinoma in 5.6%, and medullary carcinoma and adenoid cystic carcinoma in 2.2%. BLBC was most often associated with a high tumor grade (55.3% had a grade 3 tumor) and a high Ki-67 proliferative index. Vascular invasion was found in 31.1% of the cases. Regarding lymph node involvement, 42.9% had positive lymph nodes and 7.9% featured distant metastases. Surgical treatment was provided for 85 patients. It consisted of conservative surgery in 40 cases and radical surgery in 45 cases. Neoadjuvant chemotherapy was administrated to 23 patients, with a 13% complete pathologic response. The rates of overall survival and disease-free survival at 3 years for localized BLBC were 74.4% and 75.9%, respectively. Conclusion: BLBCs are aggressive tumors associated with poor prognosis. Thus, to identify novel prognostic factors and therapeutic targets, prospective studies should investigate the epidemiological and evolutive profile of these tumors.

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