Evaluation of BRCA1 and BRCA2 Protein Dysfunction in Breast Cancer Cells among Women in Osun State, Southwest Nigeria

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S118-S119
Author(s):  
S Iyiola ◽  
A Komolafe ◽  
A Samuel ◽  
J A Onifade ◽  
I Enweani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
University Teaching ◽  
Teaching Hospitals ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Cross Sectional ◽  
Brca2 Protein ◽  
Brca 1 ◽  
Brca 2

Abstract Introduction/Objective Breast cancer among Nigeria women had been found to occur at a much younger age compared with their Caucasian age groups. BRCA1 and BRCA2 were suspected to responsible for breast cancers at a young age, therefore this work examined the BRCA1 and BRCA2 dysfunction among women suffering from breast cancer in Osun State, Nigeria. Methods This cross-sectional study was carried out at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife and Ladoke Akintola University Teaching Hospital, Osogbo, Nigeria. The request cards and tissue blocks were sorted from the year 2014 to 2017. The breast tissue blocks were sectioned, stained with H&E. A representative tissue block was selected for each patient. Sections obtained from the blocks were stained with BRCA 1 and BRCA 2 antibody using a diaminobenzidine horseradish peroxidase technique. The cells were semi-quantitatively scored as percentage of tumour cells stained brown. Score 0-5% were taken as negative as proposed by Karuna et al., 2013. The value obtained was tabulated against the age of the patient. Results Out of 240 breast cancer patients sampled 16(6.7%), 32(13.3%), 85(35.4%), 43(17.9%), 64(26.7%) patients were between ages 21-30, 31-40, 41-50, 51-60 and 60+ years respectively. 54(22.5%) showed loss of BRCA 1 staining with only 1(0.4%) patient between age 21-40 years while 18(7.5%), 16(6.67), 19(7.9) patients between age 41-50, 51-60 and 60+ years respectively. 82(34.2%) showed loss of BRCA 2 staining; 7(2.9%), 12(5%), 31(12.9%), 15(6.25%),17(5.8%) patients for age between 21-30, 31-40, 41-50, 51-60 and 60+ years respectively. Among women aged 50 years and below, BRCA 1 and BRCA 2 dysfunctions were responsible for 14.3% and 37.6% of breast cancers respectively. Conclusion Increase in age increases the rate of BRCA 1 dysfunction while BRCA 2 dysfunction is not more associated to with any age. BRCA1 and BRCA2 are responsible for more than thirty percent of breast cancers among women less than 50 years of age in Osun state.

scholarly journals Estimating the weighted prevalence of anxiety disorders in breast cancer patients using a Two-stage approach

2018 ◽  
Vol 4 (1) ◽  
pp. 7-15
Author(s):  
Olamijulo A Fatiregun ◽  
Oluseun Peter Ogunnubi ◽  
Omolara A Fatiregun ◽  
Bolutife O Oyatokun ◽  
Osunwale Dahunsi Oni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Anxiety Disorder ◽  
Anxiety Disorders ◽  
Depression Scale ◽  
Diagnostic Interview ◽  
University Teaching ◽  
Diagnostic Tools ◽  
Breast Cancer Patients ◽  
Two Stage ◽  
Cross Sectional

Background: A two-stage survey is useful when the actual diagnostic interview is time-consuming and expensive to administer on the general population. Objective: To compare Schedule for Clinical Assessment in Neuropsychiatry (SCAN) with Hospital Anxiety and Depression Scale (HADS) in the determination of the prevalence of anxiety disorder in patients with breast cancer. Methods: A cross-sectional study of 200 female patients diagnosed with breast cancer attending the Oncology Out-Patients Clinic of the Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria was done. The instruments used for the survey included a socio-demographic questionnaire, the HADS and the SCAN. Results: The mean age of the subjects was 49.6 ± 11.2 years. Majority of the subjects (76.5%) were married. Using HADS with a threshold score of ≥ 8, 53 (26.5%) met the criteria for probable anxiety disorders (herein called ‘cases’). Of the 68 patients (all 53 ‘cases’ plus 15 randomly selected 10% of the non-cases) interviewed with the SCAN instrument, only 38 met the criteria for diagnosis of anxiety disorder. Conclusions: The prevalence of anxiety disorders can be determined with greater precision using the two-stage design approach. Diagnostic tools like SCAN should therefore be incorporated in the assessment protocols for patients with breast cancer and other illnesses.

scholarly journals Androgen Receptor Expression in Triple-Negative Breast Cancer

2019 ◽  
pp. 90-94
Author(s):  
Samane Jam ◽  
Alireza Abdollahi ◽  
Sanaz Zand ◽  
Zahra Khazaeipour ◽  
Ramesh Omranipour ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Androgen Receptor ◽  
Triple Negative Breast Cancer ◽  
Lymphovascular Invasion ◽  
Triple Negative ◽  
Tumor Grade ◽  
Receptor Expression ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cross Sectional

Background: Triple-negative breast cancer (TNBC) accounts for 15 to 20% of all breast cancers. These patients do not benefit from hormone therapy and other targeted treatments of breast cancer. Recently, researchers proposed the use of androgen receptor (AR)-targeted therapies in this subset of patients. The rate of AR expression in TNBC patients varies from 0 to 53%. AR positivity is associated with a better outcome for breast cancer patients. The purpose of this study was to evaluate AR status in TNBC patients and its association with other demographic and pathologic features.Methods: This cross-sectional study was conducted in the Cancer Institute of Iran, affiliated with Tehran University of Medical Sciences, in 2015. Archived formalin-fixed, paraffin-embedded breast tumor blocks were evaluated to determine the AR status of the tumors. Demographic and pathologic characteristics of the patients were retrieved from the department of pathology database. Data were analyzed with SPSS 18.0.Results: Seventy-seven TNBC patients with the mean age of 45.3 ± 11.5 were assessed. Twenty-six patients (34%) showed AR expression, and 51 patients (56%) did not have AR expression. There was no significant correlation between AR status and age, tumor size, histopathologic type of tumor, or lymph node involvement. However, AR positivity had a statistically significant association with a lower tumor grade and lymphovascular invasion (P = 0.029 and P = 0.01, respectively).Conclusion: TNBC patients with AR expression tend to have lower tumor grades and higher rates of lymphovascular invasion.

scholarly journals Synchronous and Metachronous Breast Malignancies: A Cross-Sectional Retrospective Study and Review of the Literature

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ambrogio P. Londero ◽  
Sergio Bernardi ◽  
Serena Bertozzi ◽  
Vito Angione ◽  
Giuliana Gentile ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
English Literature ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Unilateral Breast Cancer ◽  
Cross Sectional

Objective. There is increasing interest in patients with metachronous (MBC) and synchronous breast cancer (SBC). The objective of this study was to evaluate the occurrence and outcome of MBCs and SBCs.Methods. A retrospective study on women operated in our department for breast cancer between 2002 and 2005 was carried out. Patients were divided into three groups: women with MBC, SBC, and unilateral breast cancer (UBC). Moreover, we performed a meta-analysis of the English literature about multiple breast cancers between 2000 and 2011 taking into consideration their prevalence and overall survival (OS).Results. We identified 584 breast cancer patients: 16 women (3%) presented SBC and 40 MBC (7%, second cancer after 72-month follow-up IQR 40–145). Although the meta-analysis showed significant OS differences between MBC or SBC and UBC, we did not observe any significant OS difference among the three groups of our population. Anyway, we found a significant worse disease-free survival in MBC than UBC and a significant higher prevalence of radical surgery in MBC and SBC than UBC.Conclusions.Despite the low prevalence of MBC and SBC, the presence of a long time risk of MBC confirms the crucial role of ipsi- and contralateral mammographies in the postoperative follow-up.

scholarly journals Prevalence and predictors of germline BRCA1 and BRCA2 mutations among young patients with breast cancer in Jordan

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikmat Abdel-Razeq ◽  
Lama Abujamous ◽  
Mahmoud Abunasser ◽  
Sara Edaily ◽  
Rayan Bater
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Young Patients ◽  
Personal History ◽  
Mutation Rates ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Variant Of Uncertain Significance

AbstractBRCA1 and BRCA2 mutations are not uncommon in breast cancer patients. Western studies show that such mutations are more prevalent among younger patients. This study evaluates the prevalence of germline mutations in BRCA1 and BRCA2 among breast cancer patients diagnosed at age 40 or younger in Jordan. Blood samples of patients with breast cancer diagnosed at age 40 years or younger were obtained for DNA extraction and BRCA sequencing. Mutations were classified as benign/likely benign (non-carrier), pathogenic/likely pathogenic variant (carrier) and variant of uncertain significance (VUS). Genetic testing and counseling were completed on 616 eligible patients. Among the whole group, 75 (12.2%) had pathogenic or likely pathogenic variants; two of the BRCA2 mutations were novel. In multivariate analysis, triple-negative disease (Odd Ratio [OR]: 5.37; 95% CI 2.88–10.02, P < 0.0001), breast cancer in ≥ 2 family members (OR: 4.44; 95% CI 2.52–7.84, P < 0.0001), and a personal history ≥ 2 primary breast cancers (OR: 3.43; 95% CI 1.62–7.24, P = 0.001) were associated with higher mutation rates. In conclusion, among young Jordanian patients with breast cancer, mutation rates are significantly higher in patients with triple-negative disease, personal history of breast cancer and those with two or more close relatives with breast cancer.

BRCAness and prognosis of triple-negative breast cancer patients treated with neoadjuvant chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12111-e12111 ◽  
Author(s):  
Sadako Akashi-Tanaka ◽  
Yuichi Tanino ◽  
Yutaka Yamamoto ◽  
Hiroshi Nishimiya ◽  
Mutsuko Yamamoto-ibusuki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Needle Biopsy ◽  
Triple Negative ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Core Needle ◽  
Brca 1 ◽  
Dna Repair Inhibitors ◽  
Dependent Probe

e12111 Background: Triple-negative breast cancers (TNBCs) consist of patients which are recalcitrant to chemotherapy. Dysfunction of BRCA, called “BRCAness” may be predictive of sensitivity to DNA repair inhibitors. However, adequate assay of “BRCAness” are still not confirmed. Multiplex ligation-dependent probe amplification (MLPA) with the Probemix P376-B2 BRCA1ness (MRC-Holland, The Netherlands) can be one method to determine BRCAness. We previously reported that “BRCAness” by MLPA predict resistance to taxane during neoadjuvant chemotherapy (NAC) and poor outcome. In the present study, we evaluated the clinical significance of BRCAness in a multicenter retrospective study. Methods: The data on 94 patients with TNBC treated with NAC were obtained from 3 hospitals in Japan. Most of them were treated by anthracyclines plus taxanes in 86 patients between 2005 and 2015. BRCAness was determined by core needle biopsy (CNB) specimens prior to NAC and surgical specimens. Genes from those specimens were amplified by MLPA, and the amplicons were scored. BRCA1-like type (BRCAness) was determined by tumors with greater than 0.5 Results: pCR (ypT0/Tis/N0) rate was 46%. Recurrence occurred in 22 patients, 11 of whom died from breast cancer. (1) BRCA1-like type accounted for 51 patients while the sporadic type in 43 patients in CNB specimens. No major differences in pCR rates and recurrence were observed between the BRCA1-like type and sporadic type (19/51 vs. 24/43), respectively. Patients with BRCA1-like tended to resist taxane than those with sporadic type when treated with taxane first. Among the 51 non-pCR patients, 19 were BRCA1-like type and 31 were sporadic type upon surgical specimens. Patients with a BRCA1-like tumors had more recurrences, than non-BRCA-1-like (13/19 vs. 9/31, respectively, P < 0.01). Conclusions: Tumors with BRCA-1 like tended to resist taxane than sporadic type when treated by taxane first. Anthracycline first might mask the progression during taxane regimen. Patients with BRCA1-like after NAC had more recurrences than those with sporadic type. Further study is needed to evaluate the significance of BRCAness.

Prognostic Role of Hedgehog-GLI1 Signaling Pathway in Aggressive and Metastatic Breast Cancers

2020 ◽  
Vol 21 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Prasuja Rokkam ◽  
Shailender Gugalavath ◽  
Deepak Kakara Gift Kumar ◽  
Rahul Kumar Vempati ◽  
Rama Rao Malla
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Neural Development ◽  
Splice Variants ◽  
Metastatic Breast ◽  
Basic Function ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Aberrant Expression ◽  
Cellular Processes

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

Association of CYP2D6*10 (c. 100 C>T) Genotype with Z-END Concentration in Patients with Breast Cancer Receiving Tamoxifen Therapy in Indonesian Population

2019 ◽  
Vol 19 (8) ◽  
pp. 1198-1206 ◽  
Author(s):  
Yenny ◽  
Sonar S. Panigoro ◽  
Denni J. Purwanto ◽  
Adi Hidayat ◽  
Melva Louisa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Steady State ◽  
Ultra Performance Liquid Chromatography ◽  
Cross Sectional Study ◽  
Threshold Concentration ◽  
Breast Cancer Patients ◽  
Cross Sectional ◽  
Significant Difference ◽  
Pcr Rflp ◽  
Liquid Chromatography Tandem Mass

Background: Tamoxifen (TAM) is a frequently used hormonal prodrug for patients with breast cancer that needs to be activated by cytochrome P450 2D6 (CYP2D6) into Zusammen-endoxifen (Z-END). Objective: The purpose of the study was to determine the association between CYP2D6*10 (c.100C>T) genotype and attainment of the plasma steady-state Z-END minimal threshold concentration (MTC) in Indonesian women with breast cancer. Methods: A cross-sectional study was performed in 125 ambulatory patients with breast cancer consuming TAM at 20 mg/day for at least 4 months. The frequency distribution of CYP2D6*10 (c.100C>T) genotypes (C/C: wild type; C/T: heterozygous mutant; T/T: homozygous mutant) was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), the results of which were subsequently confirmed by sequencing. The genotypes were categorized into plasma Z- END concentrations of <5.9 ng/mL and ≥5.9 ng/mL, which were measured using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results: Percentages of C/C, CT, and T/T genotypes were 22.4%, 29.6%, and 48.8%, respectively. Median (25-75%) Z-END concentrations in C/C, C/T, and T/T genotypes were 9.58 (0.7-6.0), 9.86 (0.7-26.6), and 3.76 (0.9-26.6) ng/mL, respectively. Statistical analysis showed a significant difference in median Z-END concentration between patients with T/T genotype and those with C/C or C/T genotypes (p<0.001). There was a significant association between CYP2D6*10 (c.100C>T) genotypes and attainment of plasma steady-state Z-END MTC (p<0.001). Conclusion: There was a significant association between CYP2D6*10 (c.100C>T) and attainment of plasma steady-state Z-END MTC in Indonesian breast cancer patients receiving TAM at a dose of 20 mg/day.

scholarly journals Iodine Map Radiomics in Breast Cancer: Prediction of Metastatic Status

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2431
Author(s):  
Lukas Lenga ◽  
Simon Bernatz ◽  
Simon S. Martin ◽  
Christian Booz ◽  
Christine Solbach ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Principal Component ◽  
Validation Dataset ◽  
Dual Energy Ct ◽  
Cancer Tissue ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Iodine Map ◽  
Iodine Maps

Dual-energy CT (DECT) iodine maps enable quantification of iodine concentrations as a marker for tissue vascularization. We investigated whether iodine map radiomic features derived from staging DECT enable prediction of breast cancer metastatic status, and whether textural differences exist between primary breast cancers and metastases. Seventy-seven treatment-naïve patients with biopsy-proven breast cancers were included retrospectively (41 non-metastatic, 36 metastatic). Radiomic features including first-, second-, and higher-order metrics as well as shape descriptors were extracted from volumes of interest on iodine maps. Following principal component analysis, a multilayer perceptron artificial neural network (MLP-NN) was used for classification (70% of cases for training, 30% validation). Histopathology served as reference standard. MLP-NN predicted metastatic status with AUCs of up to 0.94, and accuracies of up to 92.6 in the training and 82.6 in the validation datasets. The separation of primary tumor and metastatic tissue yielded AUCs of up to 0.87, with accuracies of up to 82.8 in the training, and 85.7 in the validation dataset. DECT iodine map-based radiomic signatures may therefore predict metastatic status in breast cancer patients. In addition, microstructural differences between primary and metastatic breast cancer tissue may be reflected by differences in DECT radiomic features.

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