Abstract 1697: Gadd45A expression is high in luminal A and her2 human breast cancers, but frequently absent in triple negative breast cancers

2012 ◽  
Author(s):  
Jennifer S. Tront ◽  
Alliric Willis ◽  
Yajue Huang ◽  
Geoffery Smith ◽  
Benjamin Powers ◽  
...  
Keyword(s):  
Triple Negative ◽  
Breast Cancers ◽  
Human Breast ◽  
Luminal A

scholarly journals Identification of Long Noncoding RNAs as Predictors of Survival in Triple-Negative Breast Cancer Based on Network Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Xiao-Xiao Li ◽  
Li-Juan Wang ◽  
Jie Hou ◽  
Hong-Yang Liu ◽  
Rui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Network Analysis ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Breast Cancers ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer observed in adult females, worldwide. Due to the heterogeneity and varied molecular subtypes of breast cancer, the molecular mechanisms underlying carcinogenesis in different subtypes of breast cancer are distinct. Recently, long noncoding RNAs (lncRNAs) have been shown to be oncogenic or play important roles in cancer suppression and are used as biomarkers for diagnosis and therapy. In this study, we identified 134 lncRNAs and 6,414 coding genes were differentially expressed in triple-negative (TN), human epidermal growth factor receptor 2- (HER2-) positive, luminal A-positive, and luminal B-positive breast cancer. Of these, 37 lncRNAs were found to be dysregulated in all four subtypes of breast cancers. Subtypes of breast cancer special modules and lncRNA-mRNA interaction networks were constructed through weighted gene coexpression network analysis (WGCNA). Survival analysis of another public datasets was used to verify the identified lncRNAs exhibiting potential indicative roles in TN prognosis. Results from heat map analysis of the identified lncRNAs revealed that five blocks were significantly displayed. High expressions of lncRNAs, including LINC00911, CSMD2-AS1, LINC01192, SNHG19, DSCAM-AS1, PCAT4, ACVR28-AS1, and CNTFR-AS1, and low expressions of THAP9-AS1, MALAT1, TUG1, CAHM, FAM2011, NNT-AS1, COX10-AS1, and RPARP-AS1 were associated with low survival possibility in TN breast cancers. This study provides novel lncRNAs as potential biomarkers for the therapeutic and prognostic classification of different breast cancer subtypes.

Biological and clinical features of early triple-negative invasive lobular carcinomas of the breast.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12570-e12570
Author(s):  
Fabio Conforti ◽  
Laura Pala ◽  
Elena Guerini Rocco ◽  
Eleonora Pagan ◽  
Vincenzo Bagnardi ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Luminal A ◽  
Median Percentage ◽  
Biological Features ◽  
Mutational Status ◽  
Erbb2 Gene

e12570 Background: Hormone receptors and HER2 negative (triple negative, TN) invasive lobular carcinomas (ILCs) are very rare, accounting for 1-2% of all TN breast cancers (BCs). Methods: We extracted data from our prospectively collected institutional database on all consecutive patients (pts) with early stage TN ILC operated at the European Institute of Oncology (IEO) between June 1994 and December 2012. Invasive disease-free survival (iDFS) and cumulative incidence of distant metastases (CI-DM) were calculated. Biological features of these tumors, including molecular intrinsic subtypes based on PAM50 assay, expression of androgen receptor (AR) and mutational status of c-erbB2 gene were also evaluated. Additionally, NGS data of 45 TN ILCs were obtained from 3 large public databases, to confirm mutations in c-erbB2 gene and to identify other recurrently mutated genes. Results: Among 2952 ILCs treated at IEO, 44 (1.5%) were TN and were included in the analysis. All pts received adjuvant chemotherapy. The iDFS rates at 5 and 10 years of follow-up were 47.4% (95% CI, 31.1-62.0) and 29.5% (95% CI, 14.8-45.8), respectively. The corresponding CI-DM percentages were 17.6% (95% CI, 7.6-31.2) and 20.8% (95% CI, 9.5-35.1). The molecular intrinsic subtype was defined through PAM50 for 31 out of 44 TN ILCs: 48% were classified as luminal A, 3% luminal B, 32% HER2-enriched, and only 16% basal-like. The group of pts with luminal A or B tumors had a significantly better CI-DM as compared with pts with non-luminal tumors (i.e. HER2-enriched and basal-like; p=0.003). Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 96% of luminal tumors versus 53% in non-luminal tumors; p=0.001), and at significantly higher levels (median percentage of AR-positive cells was 80% in luminal tumors versus 15% in non-luminal tumors; p=0.01). Higher AR expression was associated with significantly better iDFS in the whole cohort of TN ILCs (p=0.01), as well as in the group of luminal tumors (p=0.05). 27 TN ILCs of the IEO cohort were analyzed for mutations in c-erbB2 gene, and 9 (33%) harbored mutations. Analysis of the 3 public databases, confirmed c-erbB2 mutations in 9 out of 45 (20%) TN ILCs. All the c-erbB2 mutations found were previously reported to be pathogenetic in BCs and to predict response to neratinib. ErbB signaling and DNA damage response were among the top 10 pathways significantly enriched for mutated genes in TN ILCs. Conclusions: TN ILCs are rare tumors with dire prognosis. Their specific biological features require newly defined targeted therapeutic strategies.

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.

scholarly journals Poor Biological Factors and Prognosis of Interval Breast Cancers: Long-Term Results of Bahçeşehir (Istanbul) Breast Cancer Screening Project in Turkey

2020 ◽  
pp. 1103-1113
Author(s):  
Neslihan Cabioğlu ◽  
Sibel Özkan Gürdal ◽  
Arda Kayhan ◽  
Nilüfer Özaydın ◽  
Cennet Şahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Screening ◽  
Breast Cancer Screening ◽  
Triple Negative ◽  
Long Term Results ◽  
Breast Cancers ◽  
Interval Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

PURPOSE The Turkish Bahçeşehir Breast Cancer Screening Project was a 10-year, organized, population-based screening program carried out in Bahçeşehir county, Istanbul. Our aim was to examine the biologic features and outcome of screen-detected and interval breast cancers during the 10-year study period. METHODS Between 2009 and 2019, 2-view mammograms were obtained at 2-year intervals for women aged 40 to 69 years. Clinicopathological characteristics including ER, PR, HER2-neu, and Ki-67 status were analyzed for those diagnosed with breast cancer. RESULTS In 8,758 screened women, 131 breast cancers (1.5%) were detected. The majority of patients (82.3%) had prognostic stage 0-I disease. Contrarily, patients with interval cancers (n = 15; 11.4%) were more likely to have a worse prognostic stage (II-IV disease; odds ratio [OR], 3.59, 95% CI, 0.9 to 14.5) and high Ki-67 scores (OR, 3.14; 95% CI, 0.9 to 11.2). Interval cancers detected within 1 year were more likely to have a luminal B (57.1% v 31.9%) and triple-negative (14.3% v 1%) subtype and less likely to have a luminal A subtype (28.6% v 61.5%; P = .04). Patients with interval cancers had a poor outcome in 10-year disease-specific (DSS) and disease-free survival (DFS) compared with those with screen-detected cancers (DSS: 68.2% v 98.1%, P = .002; DFS: 78.6% v 96.5%, P = .011). CONCLUSION Our findings suggest the majority of screen-detected breast cancers exhibited a luminal A subtype profile with an excellent prognosis. However, interval cancers were more likely to have aggressive subtypes such as luminal B subtype or triple-negative cancers associated with a poor prognosis requiring other preventive strategies.

scholarly journals Surface Expression of Kynurenine 3-Monooxygenase Promotes Proliferation and Metastasis in Triple-Negative Breast Cancers

2021 ◽  
Vol 28 ◽  
pp. 107327482110092
Author(s):  
Min-Hua Lai ◽  
Chi-Hsun Liao ◽  
Nu-Man Tsai ◽  
Kai-Fu Chang ◽  
Cheng-Chi Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cell Membranes ◽  
Triple Negative ◽  
Cancer Cell Line ◽  
Surface Expression ◽  
Migration And Invasion ◽  
Mitochondrial Outer Membrane ◽  
Breast Cancers ◽  
Human Breast

Kynurenine 3-monooxygenase (KMO) is the pivotal enzyme in the kynurenine pathway and is located on the mitochondrial outer membrane. The dysregulation of KMO leads to various neurodegenerative diseases; however, it is rarely mentioned in cancer progression. Our previous study showed that KMO overexpression in canine mammary gland tumors (cMGT) is associated with poor prognosis in cMGT patients. Surprisingly, it was also found that KMO can be located on the cell membranes of cMGT cells, unlike its location in normal cells, where KMO is expressed only within the cytosol. Since cMGT and human breast cancer share similar morphologies and pathogenesis, this study investigated the possibility of detecting surface KMO in human breast cancers and the role of surface KMO in tumorigenesis. Using immunohistochemistry (IHC), flow cytometry (FC), immunofluorescence assay (IFA), and transmission electron microscopy (TEM), we demonstrated that KMO can be aberrantly and highly expressed on the cell membranes of breast cancer tissues and in an array of cell lines. Masking surface KMO with anti-KMO antibody reduced the cell viability and inhibited the migration and invasion of the triple-negative breast cancer cell line, MDA-MB-231. These results indicated that aberrant surface expression of KMO may be a potential therapeutic target for human breast cancers.

scholarly journals Comparison of Different Molecular Subtypes with 14% Ki-67 Cut-off Threshold in Breast Cancer Patients of Pakistan- An Indication of Poor Prognosis

2021 ◽  
Vol 24 (11) ◽  
pp. 837-844
Author(s):  
Mehreen Mushtaq ◽  
Summaya Sohail Chaudry ◽  
Ahmareen Khalid Sheikh ◽  
Nazia Khan ◽  
Asma Khattak ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Histological Grade ◽  
High Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Ki 67 ◽  
Therapeutic Decisions

Background: Ki-67 is a proliferation marker that is used not only to categorize patients in luminal A and B subtypes of breast cancers, but also to determine the aggressiveness of the disease in triple negative and human epidermal growth factor 2 (HER2) over expressed molecular subtypes. The present study was designed to evaluate the role of Ki-67 with cut off value of 14% in molecular subgroups and its association with patient prognosis. Methods: Immunostaining was performed on histopathologically confirmed sections (n = 278) to assess expression of Ki-67, estrogen receptor (ER), progesterone receptor (PR) and HER2. Immunoreactivity of molecules was recorded as percentage scoring. Results: Adopting a cut off value of 14%, Ki-67 was high in 88%of the cases included in the study. High Ki-67 was significantly associated with pathological parameters including histological grade, advanced stage and nodal/distant metastasis. Immunoexpression of ER, PR and HER2 also showed strong correlation with high expression of Ki-67. Based on the St. Gallen classification, the cases were categorized into luminal A (10%) and luminal B (51%), triple negative (20%) and HER2 enriched (18%). Ki-67 index was also significantly high in 98% of HER2 enriched and 95% of TNBC patients. Interestingly, Ki-67 score with cut off value of 14% proved to be significant in deciphering prognosis in luminal patients. Moreover, high expression of Ki-67 also proved to be a marker of poor prognosis, especially in triple negative patients. Conclusion: We suggest that utilization of IHC4 status i.e. ER, PR, HER2 and Ki-67 along with pathological findings and molecular subtyping can considerably affect clinical as well as therapeutic decisions.

scholarly journals A study of conventional histological parameters in excision specimens of breast cancer over a 7 year period and association with immunohistochemical categories

2020 ◽  
Author(s):  
Parikshit Sanyal ◽  
Anshuman Singh ◽  
Prosenjit Ganguli ◽  
Sanghita Barui
Keyword(s):  
Breast Cancer ◽  
Lymphovascular Invasion ◽  
Triple Negative ◽  
Morphological Characteristics ◽  
Lymph Node Involvement ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Node Involvement ◽  
Neo Adjuvant Chemotherapy

AbstractBackgroundAlong with conventional histological examination, immunohistochemistry (IHC) is a useful adjunct to assessment of a breast cancer excision specimen. Previous studies have shown differences in behavior of neoplasms depending on their histopathological as well as immunohistochemical categories; in particular, triple negative breast cancers (on IHC) show the worst prognosis.ObjectivesTo find association, if any, within conventional histopathological characteristics (size, grade, stage, mitotic count, desmoplasia, dense inflammatory infiltrate, lymphovascular invasion) and between the conventional parameters and immunohistochemical categories of breast cancer, in both primary and post neo adjuvant chemotherapy (NACT) specimens.Methods177 breast cancer excision specimens examined over last 7 years were assessed retrospectively, their histopathological parameters were recorded. In cases where immunohistochemistry was performed (N=108) the specimen was placed in one of the immunohistochemical categories: Luminal A, Luminal B, Her2 and Triple negative cancers. The data was then analysed by standard statistical methods.ResultsNo statistically significant association was found between the histopathological parameters and IHC category was. However, a strong correlation was seen between lymphovascular invasion within the primary tumor and increasing lymph node involvement. There was also a reduction in ER and PR expression in neoplasms post NACT, while HER2 expression remained largely unchanged.ConclusionThere might be additional genetic subtypes underlying the immunohistochemical phenotypes which determine the morphological characteristics of the neoplasm.

scholarly journals Immunohistochemical Profile of Molecular Markers of Mammary Carcinomas in Libreville

2021 ◽  
Vol 2 (2) ◽  
pp. 55-62
Author(s):  
Barthélemy Mabika ◽  
Nicole Josiane Andeme ◽  
Sidonie Solange Nguizi Ogoula ◽  
Guy Joseph Lémamy
Keyword(s):  
Molecular Markers ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Molecular Classification ◽  
Breast Cancers ◽  
Luminal A ◽  
Mammary Carcinomas ◽  
Luminal B ◽  
Immunohistochemical Profile

To establish the immunohistochemical profile of the molecular markers of free-ranging breast carcinomas. Descriptive retrospective study over 3 years from July 2014 to September 2017. The tumour samples came from the Anatomical Pathology Laboratories of the Omar Bongo Ondimba Army Instruction Hospital and the University of Health Sciences. In total, the records of 60 patients with histologically proven breast carcinoma with the immunohistochemical study were included in the study. The following molecular markers, hormone receptors (estrogen receptors, progesterone receptors), the HER2/Neu oncogene, and the Ki67 cell proliferation marker, was identified using the Immunohistochemistry technique.The average age was 47.6 years, with extremes of 15 and 69 years. Depending on the location, the right breast was most commonly affected (50%). Histologically, there was a predominance of infiltrating ductal carcinomas (66.6%) and a majority SBR III grade (50%). This study revealed an immunohistochemical profile of positive hormone receptors: ERs + (13.3%); PRs + (8.3%) and a Ki67 profile positive in 10% of tumors. The molecular classification into 4 subtypes (Luminal A, Luminal B, HER2 and Triple Negative) places the Luminal A group in the first rank (33.3%) followed by the Luminal B (15%), Triple Negative (11.6%) and HER2 (8.3%). The present work is the first study reporting the immunohistochemical profile of molecular markers of mammary carcinomas in Gabon. It would be necessary to continue this study on a larger and wider cohort throughout Gabon because the knowledge of the immunohistochemical profile gives an indication of the origin of breast cancers and allows to consider better management of patients by a targeted therapy to avoid unnecessary toxic effects resulting from ineffective treatment.

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