scholarly journals Clinical Significance of ARID1A and ANXA1 in HER-2 Positive Breast Cancer

2020 ◽  
Vol 9 (12) ◽  
pp. 3911
Author(s):  
Rita Silva-Oliveira ◽  
Filipa Ferreira Pereira ◽  
Sara Petronilho ◽  
Ana Teresa Martins ◽  
Ana Lameirinhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Stage ◽  
Breast Cancer Mortality ◽  
Inverse Association ◽  
Patient Stratification ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Luminal B ◽  
Her 2

Background: trastuzumab is considered the standard of care for human epidermal growth factor receptor-2 (HER-2+) breast cancer patients. Regardless of the benefits of its use, many early-stage patients eventually recur, and usually, the disease progresses within a year. Since about half of the HER-2+ patients do not respond to trastuzumab, new biomarkers of prognosis and prediction are warranted to allow a better patient stratification. Annexin A1 (ANXA1) was previously reported to contribute to trastuzumab resistance through AKT activation. An association between adenine thymine-rich interactive domain 1A (ARID1A) loss and ANXA1 upregulation was also previously suggested by others. Methods: in this study, we examined tissue samples from 215 HER-2+ breast cancer patients to investigate the value of ARID1A and ANXA1 protein levels in trastuzumab response prediction and patient outcome. Expression of ARID1A and ANXA1 were assessed by immunohistochemistry. Results: contrary to what was expected, no inverse association was found between ARID1A and ANXA1 expression. HER-2+ (non-luminal) tumours displayed higher ANXA1 expression than luminal B-like (HER-2+) tumours. Concerning trastuzumab resistance, ARID1A and ANXA1 proteins did not demonstrate predictive value as biomarkers. Nevertheless, an association was depicted between ANXA1 expression and breast cancer mortality and relapse. Conclusions: overall, our results suggest that ANXA1 may be a useful prognostic marker in HER-2+ patients. Additionally, its ability to discriminate between HER-2+ (non-luminal) and luminal B-like (HER-2+) patients might assist in patient stratification regarding treatment strategy.

High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer.

1997 ◽  
Vol 15 (11) ◽  
pp. 3363-3367 ◽  
Author(s):  
M L Disis ◽  
S M Pupa ◽  
J R Gralow ◽  
R Dittadi ◽  
S Menard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Specific Antibody ◽  
Primary Tumor ◽  
Early Stage ◽  
High Titer ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Specific Antibodies ◽  
Her 2

PURPOSE To evaluate HER-2/neu-specific antibody immunity in patients with breast cancer, to determine the rate of occurrence of serum antibodies to HER-2/neu in patients with breast cancer, and to relate the presence of specific immunity to overexpression of HER-2/neu protein in primary tumor. METHODS The antibody response to HER-2/neu protein was analyzed in 107 newly diagnosed breast cancer patients. Sera was analyzed for the presence of HER-2/neu-specific antibodies with a capture enzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population. RESULTS The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of > or = 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (0%) normal controls (P < .01). The presence of antibodies to HER-2/neu also correlated to overexpression of HER-2/neu protein in the patient's primary tumor. Nine of 44 (20%) patients with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, whereas three of 63 (5%) patients with HER-2/neu-negative tumors had antibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). CONCLUSION The presence of HER-2/neu antibodies in breast cancer patients and the correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu protein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic proteins as tumor markers, as well as the development and testing of vaccine strategies to induce and augment immunity to HER-2/neu for the treatment of breast cancer or prevention of recurrent disease.

scholarly journals Exosomal Long Noncoding Rna AGAP2-AS1 Regulates Trastuzumab Resistance via Inducing Autophagy in Breast Cancer

2020 ◽  
Author(s):  
Mingli Han ◽  
Hongbo Qu ◽  
Hui Cao ◽  
Xiangke Li ◽  
Dongwei Dou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Regulatory Function ◽  
Cancer Resistance ◽  
Breast Cancer Patients ◽  
Trastuzumab Resistance ◽  
Her 2

Abstract Background: Trastuzumab has been widely used for treatment of HER-2-positive breast cancer patients, however, the clinical response has been restricted due to emergence of resistance. Recent studies indicate that long noncoding RNA AGAP2-AS1 (lncRNA AGAP2-AS1) plays an important role in cancer resistance. However, the precise regulatory function and therapeutic potential of AGAP2-AS1 in trastuzumab resistance is still not defined. Methods: Trastuzumab resistant cells were established. RNA sequencing and qRT-PCR were performed to identify the target gene of AGAP2-AS1. Mass spectrometry, RNA pulldown and RNA immunoprecipitation assays were performed to verify the direct interactions among AGAP2-AS1 and other associated targets, such as embryonic lethal abnormal version like RNA binding protein 1 (ELAVL1) and autophagy related 10 (ATG10). In vitro and in vivo experimental assays were done to clarify the functional role of exosomal AGAP2-AS1 in trastuzumab resistance.Results: AGAP2-AS1 promotes and disseminates trastuzumab resistance via packaging into exosomes. Exosomal AGAP2-AS1 induces trastuzumab resistance via modulating ATG10 expression and autophagy activity. Mechanically, AGAP2-AS1 is associated with ELAVL1 protein. The AGAP2-AS1-ELAVL1 complex could directly bind to the promoter region of ATG10, inducing H3K27ac and H3K4me3 enrichment, which finally activates ATG10 transcription. AGAP2-AS1-targeting antisenseoligonucleotides (ASO) substantially increased trastuzumab-induced cytotoxicity. Clinically, increased expression of serum exosomal AGAP2-AS1 was associate with poor response to trastuzumab treatment.Conclusion: ExosomalAGAP2-AS1 increased trastuzumab resistance via promoting ATG10 expression and inducing autophagy. Therefore, AGAP2-AS1 may serve aspredictive biomarker and therapeutic target for HER-2+ breast cancer patients.

scholarly journals Molecular Subtypes of Breast Cancer Patients According to St Gallen Classification

2020 ◽  
Vol 19 (1) ◽  
pp. 55-58
Author(s):  
Shafatujjahan ◽  
Ifatujjahan ◽  
Rajat Sanker Roy Biswas
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtypes ◽  
Hormonal Treatment ◽  
Left Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Her 2

Introduction: Breast cancer is a common malignancy among female in Bangladesh.But its molecular subtypes are not evaluated due to lack of expert investigationsupport. So objectives of the present study are to evaluate the molecular subtypesof breast cancer patients according to St Gallen classification in our contest. Materials and methods: It is retrospective study done among histopathologicallyproved 40 breast cancer patients visiting Medical Oncology and Radiotherapydepartment of Chattogram Maa-O-Shishu Hospital. Molecular subtypes wasevaluated by immunohistochemistry according to St Gallen Classification. Results: In this study a total of 40 cases of invasive female breast cancers wereincluded. Age of the patients ranged from 31-62 years, with a mean age of 41 ±13.5 years. ER expression was seen in 60% and PR in 55% of cases and Her-2/neupositivity in 16%. Majority (52.5%) of the tumors were located in the left breast. Thepercentage of ER but not PR positivity increased with age, though this differencewas not statistically significant. Majority of the cases were diagnosed at stage IIwith a percentage of 42.5%. Stage II tumors showed more ER and PR positivity.Among all 57.9% of ER positive and 49.5% of PR positive tumors were present while72.2% of tumors were negative for Her-2/neu. The triple-negative breast tumorswere more commonly found at grade 2. Regarding luminal status 14(35%) wasLuminal A, 5(12.5%) was Luminal B, 9(22.5%) was TNBC and 12(30%) was HER 2positive. Conclusion: In this study luminal A was the commonest molecular subtypes. LuminalA subtypes tumors had a long term risk of distant matastatic disease which can bereduced by hormonal treatment. Chatt Maa Shi Hosp Med Coll J; Vol.19 (1); January 2020; Page 55-58

The role of Ki-67 in molecular breast cancer classification.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 583-583
Author(s):  
George Stathopoulos ◽  
Nikolaos Malamos ◽  
Christos Markopoulos ◽  
Athanasios Polychronis ◽  
Sotirios Rigatos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Progesterone Receptors ◽  
Molecular Classification ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Her 2

583 Background: The Ki-67 antigen was identified the involvement in early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that the protein has an important function in cell division, its exact role is still obscure and there is little published work on its overall function. The aim of the present study is to evaluate the contribution of Ki-67 level in respect of tumor recurrence in molecular classified groups of breast cancer patients. Methods: Breast cancer tumor samples were examined for histological confirmation and for estrogen and progesterone receptors, c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided in percentage levels, up to 20 and higher than 20%. Immunohistochemistry and Fluorescence in situ hybridization is described for the results of ER, PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were paraffin wax embedded and processed for paraffin sections. The primary antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation, Carpinteria, CA) for the detection of ER, the monoclonal anti-PR antibody 636 was used. For the detection of Ki-67 we used monoclonal mouse anti-human Ki-67 MIB-1. The patients molecular classification was Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative). Results: 847 breast cancer patients were recruited. 291 were group as Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative. Follow-up was from 3 years to 15 years since diagnosis. It was found that in Luminal A patients, none had Ki-67 higher than 20% and the recurrence was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of the patients and recurrence 23.68%. In Her-2 subtype >20% Ki-67 was 78.94%, recurrence 17.19%. In triple negative > 20% Ki-67 was in 68.75% and recurrence in 29.90% of the patients. Conclusions: The data presented here indicate that Ki-67 level may be considered as one of valuable biomarkers in breast cancer patients process and recurrence.

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