Egyptian Breast Cancer Patients Research Articles

The functional TNF-α-308G > a single-nucleotide polymorphism (rs1800629): association with the predictive indices of breast cancer carcinogenesis.

Compared with all other cancer types, Breast cancer (BC) among women has now exceeded them all as the primary reason for cancer worldwide. The BC represents 11.7% of all cancer cases and accounts for a predestined 2.3 million new cases. It is the fourth primary reason for cancer-associated deaths in women. With a staggering 200-400% increase in the relative incidence of BC in Egypt, there is an urgent need for new diagnostic or predictive markers. The current investigation aims to explore the connection of the functional TNF-α-308G > A (rs1800629) single-nucleotide polymorphism (SNP) with different breast cancer predictive indices. The ARMS-PCR method was used for genotyping TNF-α-308G > A SNP. Three groups were recruited for the study: 79 patients with benign breast inflammation (BBI); 163 with breast cancer (BC) and 144 controls (C). The TNF-α-308G > A SNP was distributed among different groups in a unique pattern; in the control group 63.9% of cases were in the GG, 34% were in the GA, and 2.1% were in the AA. The BC group had 14% GG, 79% GA, and 7% AA, while the BBI group had 24% GG, 76% GA, and 0% AA. The AA genotype and A allele represented a strong significant correlation with risk factors in the BC group (ORAA: 14.67 [95% CI = 3.78-56.91] and ORA: 0.27 [95% CI = 0.19-0.39], respectively; P < 0.0001) in contrast to the control group. However, in the BBI group, a strong significant correlation was noted with the GA genotype (ORGA: 5.93 [95% CI = 3.18-11.04] P < 0.0001). In the BC group, the AA genotype shows a significant increase in Nottingham Prognostic Index (NPI) in positive ER and PR in contrast to the relevant negative ones (P = 0.02 and 0.002, respectively). However, the GA genotype significantly increased NPI in positive Her2 and metastatic patients (P = 0.03 and 0.01, respectively). This research is the first to correlate TNF-α-308G > A (rs1800629) SNP in Egyptian BC patients. The A allele, GA & AA genotypes, and the Overdominant model of the TNF-α-308G > A gene variants were recorded as prognostic risk factors for BC carcinogenesis.

The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients

PurposeMacrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC.MethodsA total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case–control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay.ResultsA significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk.ConclusionsThis study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.Graphical

Abstract 3014: Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients

Abstract Background: Recognizing the complexity of viral carcinogenesis and its perspectives, we aimed to investigate one of the key genetic factors associated with breast cancer development, BRCA1,2 mutations, and its association with the presence of some oncogenic viruses like HPV, MMTV, and EBV DNAs in both blood and tissues of breast cancer (BC) patients, hoping to provide new insights on role of oncogenic viruses in cancer development. Patients and Methods: This study was conducted on 84 tissues and blood samples from Egyptian BC women and 50 blood samples from controls without known oncological disease. All samples were tested for the presence of viral DNAs, using real-time PCR assay. Fifty-five BC patients were investigated for the presence of mutations in exons 6 and 9 of BRCA1, and exons 11, 14, and 27 of BRCA2 using a high-resolution melting (HRM) assay. Results were correlated with the clinicopathological characteristics of BC. Results. HPV, MMTV, and EBV DNAs were detected in 30(35.7%), 19(22.6%), and 23 (27.3%) of tissues obtained from 84 BC patients, respectively, and into 16 (19%), 14 (16.7%) and 0 (0%) of blood from the same patients, respectively. On the other hand, these viruses were detected in 0 (0%), 7 (14%), and 0 (0%) of blood specimens obtained from 50 normal controls, respectively. Among 55 BC patients, mutations were detected in 37 (67%) of the tested exons of BRCA1/2 genes in the blood of BC patients, divided as 7 (12.7%) for exons 6 and 9 of BRCA1 gene, and into 11 (20%), 3 (5.5%), and 9 (16.4%) for exons 11, 14 and 27 of BRCA2 gene. Our previous investigation based on NGS showed that pathogenic mutations were (G509A:p.R170Q and c.C1471T:p.Q491X) for exons 6, 9 of BRCA1, respectively, and were (cT4001A: p.L1334X, c.7231delA: p.T2412Lfs and c.T9861A: p.C3287x) for exons 11, 14 and 27 of BRCA2, respectively. Further analysis showed that half of the patients with positive HPV DNA in tissues had mutations in the tested exons of BRCA1/2 genes. In contrast, none of the patients with MMTV DNA (15/55 (27%)) in their tissues had mutations in exons 6 and 9 of BRCA1 and only one patient had a mutation in exons 11 of BRCA2. Regarding EBV, 35% of positive patients had mutations in the tested exons of the BRCA1 gene and 21% in the tested exons of BRCA2 gene. Results were not affected by clinicopathological parameters. Conclusion: MMTV DNA followed HPV, and then EBV DNAs were detected in more than 80% of our BC patients. HPV was the most frequent virus among BC patients showed to be associated with BRCA1/2 mutations in the tested exons. Sequencing analysis is in progress. Understanding this association will provide a relevant implication for developing novel, and personalized therapeutic options for treatment of oncogenic viruses. Citation Format: Samah Loutfy, Rania Abdulmonem Al Najar, Sarah ElSayed, Nasra Abdel Fattah, Ayman Abdel-Samie Gaber, Tarek Hashem, Wafaa S. Khalaf, Ahmed F. Basyony, Amany El-Sharif, Sahar Mohamed Ramzy Radwan, Mohamed Eltokhy. Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3014.

Effects of pharmacogenetics on pharmacokinetics and toxicity of doxorubicin in Egyptian breast cancer patients

This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients with breast cancer. Patients administered DOX (60 mg/m2) for 4 cycles every 3 weeks. The peak DOX plasma concentration was measured using a validated chromatographic method. The genotyping for the selected SNPs, SLC22A16 T > C (rs714368), and CBR1 C > T (rs20572), was performed by RT-PCR. Patients were monitored for hematological and cardiac toxicities. The variant carriers of CBR1 C > T (rs20572) exhibited significantly higher DOX concentration, but no significant association to DOX-induced hematological toxicity. On the other hand, SLC22A16 T > C (rs714368) had no significant influence on DOX plasma concentration, but was significantly correlated with lower risk of neutropenia (OR 0.31, 95% CI 0.12–0.75, p = 0.01) and leukopoenia (OR 0.18, 95% CI 0.07–0.5, p = 0.001). DOX-related cardiotoxicity was correlated with the cumulative dose of DOX (R = 0.238, p = 0.017), but not with any of the two examined SNPs. Genetic polymorphisms in SLC22A16 and CBR1 may explain the inter-individual variations in DOX pharmacokinetics and toxicity. Using pharmacogenetic testing is important to customise drug therapy for cancer patients treated with anthracyclines.

Effect of lithium on chemotherapy-induced neutropenia in Egyptian breast cancer patients; a prospective clinical study.

Myelosuppressive chemotherapy-induced neutropenia (CIN) remains a major limitation of cancer treatment efficacy, necessitating very expensive supportive care. Lithium carbonate, an inexpensive drug, can increase the number of neutrophils, possibly providing an efficacious and cost-effective alternative for treating CIN. The aim of this study was to determine whether lithium therapy can attenuate chemotherapy-induced neutropenia and leukopenia in breast cancer patients. A total of 50 breast cancer patients were enrolled in this prospective, interventional, randomized, controlled, and single-blind study. The patients were divided into two groups: a control group (group 1, N = 25 patients) and a lithium-treated (treatment) group (group 2, N = 25 patients). Group 1 patients were further subclassified into a non-neutropenic control group (N = 16) and a neutropenic control (N = 9) based on the subsequent development of severe neutropenia, or not. The control group received 4 cycles of doxorubicin or epirubicin plus cyclophosphamide followed by 2 cycles of paclitaxel. The treatment group received the same regimen as the control group as well as oral lithium carbonate throughout the chemotherapy cycles. The results showed that the absolute neutrophil count (ANC) was increased in the lithium-treated group, while it was markedly reduced in both the non-neutropenic and neutropenic control groups (by 55.56% and 65.42% post-4 chemotherapy cycles, and by 19.57% and 39.90% post-6 cycles, respectively). The same pattern of alterations was observed for the total white blood cell count in both the control and treatment groups. In addition, the incidence and period prevalence were greatly reduced in the lithium-treated group compared to non-neutropenic and neutropenic control groups. Lithium therapy ameliorated chemotherapy-induced leukopenia and neutropenia in breast cancer patients. This may provide a new strategy for cost-effective treatment of CIN, particularly in Egyptian cancer patients.

Circulating ESR1, long non-coding RNA HOTAIR and microRNA-130a gene expression as biomarkers for breast cancer stage and metastasis

Breast cancer, the most prevalent cancer among women, has posed a significant challenge in identifying biomarkers for early diagnosis and prognosis. This study aimed to elucidate the gene expression profile of Estrogen Receptor-1 (ESR-1), long non-coding RNA HOTAIR, and microRNA-130a in the serum of Egyptian breast cancer patients, evaluating the potential of HOTAIR and miR-130a as biomarkers for predicting pathological parameters in BC. The study involved 45 patients with primary BC, with serum samples collected preoperatively and postoperatively twice. The expression levels of ESR-1, HOTAIR, and miR-130a were quantified using real-time PCR and analyzed for correlations with each other and with the clinical and pathological parameters of the patients. Serum HOTAIR levels exhibited a strong positive association with metastasis and demonstrated a significant increase after 6 months in all patients with locally advanced and stage IV BC. Conversely, tumors with advanced stages and metastatic lesions showed significantly lower expression levels of miR-130a. Notably, a significant positive correlation was observed between preoperative ESR-1 expression and both HOTAIR and miR-130a levels. Serum HOTAIR and miR-130a levels have emerged as promising non-invasive biomarkers with the potential to predict the pathological features of BC patients. HOTAIR, an oncogenic long non-coding RNA (lncRNA), and miR-130a, a tumor suppressor miRNA, play crucial roles in tumor progression. Further investigations are warranted to elucidate the intricate interplay between HOTAIR and miR-130a and to fully comprehend the contribution of HOTAIR to BC recurrence and its potential utility in early relapse prediction.

Genetic Polymorphism in FSCN1 rs3801004 C/G and CD44 rs353639 A/C, as Prognostic Factor in Egyptian Breast Cancer Patients.

One of the main causes of cancer-related deaths is breast cancer. Fascin-1(FSCN1) is an actin-binding protein that is present in the mesenchymal, neuronal, and endothelial cells of mammals. Patients with breast cancer have been found to have FSCN1 overexpression. CD44 is crucial for the development, invasion, and tumour spread. Therefore, we aimed to investigate the role of FSCN1&CD44 gene polymorphisms in breast cancer (BC) risk and prognosis. A total of 96 BC patients and 50 controls were included in the case-control study for risk prediction. We examined the association between The SNPs on FSCN1(rs3801004) and CD44(rs353639) and BC susceptibility and clinicopathological features using a real-time PCR in a cohort of the Egyptian population. Results: A significant association of both SNPs on FSCN1(rs3801004)C allele and CD44(rs353639)A allele and BC susceptibility(adjusted OR=4.38,95%CI:2.6-7.4,p<0.001, and adjusted OR=4.44,95%CI:2.65-7.44,p <0.001,respectively). Moreover, CC genotype in FSCN1(rs3801004) were likely to progress to developing G2&G3 and N2&N3 and stage II & stage IV, according to the TNM staging and GG+GC genotypes increased within individuals who had a positive family history of BC. Individuals who carry at least one A allele for CD44rs353639 were likely to progress developing N2 according to the TNM in BC patients. These findings suggest that both SNPs on FSCN1 (rs3801004) and CD44 (rs353639) affected BC susceptibility. FSCN1 (rs3801004) genetic variants may have a significant effect on BC prognosis. However, CD44 (rs353639) affected lymph node invasions in BC patients.

Prognostic Significance Of FOXP3+ Tumour-Infiltrating Tregs In Egyptian Breast Cancer Patients.

To evaluate the prognostic importance of tumour-infiltrating forkhead box P3 protein + regulatory T cells in breast cancer patients. The case-control study was conducted from January 2020 to March 2021 at the Kafrelsheikh University Hospital, Egypt, and comprised individuals with newly-diagnosed breast cancer who underwent conventionalsurgery, and controls who had a fibrocystic change of the breast. The density of tumour-infiltrating forkhead box P3 protein + regulatory T cells was assessed by immunohistochemistry. Overall survival and disease free-survival were assessed. Data was analysed using SPSS 25. Of the 100 patients having mean age 44.9±9.1 years, 76(76%) had moderate/strong forkhead box P3 protein expression in tumour-infiltrating regulatory T cells, and 24(24%) with no/low expression. On follow-up, Patients with moderate/strong expression had a significantly greater rate of recurrence (p<0.05). Disease-free survival was substantially shorter in patients with moderate/strong expression compared to those with little or low expression (p=0.035). Compared to individuals with no/low expression, patients with moderate/strong expression had a greater rate of mortality, but the difference was not statistically significant (p>0.05). High density of forkhead box P3 protein + regulatory T cellsin Egyptian women with breast cancer may serve as a prognostic indicator.

Predictive value of biological markers in loco-regional recurrence of breast cancer after mastectomy and radiotherapy

Objective To assess the prognostic usefulness of the human epidermal growth factor receptor-2 (Her 2), the progestin receptor (PR), and the oestrogen receptor (ER) in locoregional recurrence following mastectomy radiotherapy in Egyptian breast cancer patients. Patients and methods This retrospective analysis comprised 432 female patients who had received radiation and had a mastectomy and immunohistochemistry reports. The Ethics Committee’s clearance was required before this study could be carried out at the Ain-Shams University hospitals. Results A total of 24 individuals developed LRR after a median follow-up period of 68.9 months. Although lymph nodes with more than three exhibited a statistically significant risk for LLR, tumour grade and pT were not significant risk factors. LRR risk rose for those who were HER2-positive and those with TNBC, but Luminal B had a non-significantly greater risk than Luminal A. Conclusion For breast cancer patients receiving PMRT, the biological subtype based on the categorization standard from the St. Gallen International Breast Cancer Conference (2013) Expert Panel acts as an accurate prognostic predictor. In HER2-positive and hormonal receptor-positive individuals, trastuzumab treatment significantly reduced the risk of LRR.

Prevalence of TP53 gene Pro72Arg (rs1042522) single nucleotide polymorphism among Egyptian breast cancer patients

BackgroundThe P53 protein has an essential role in several cellular processes, including DNA repair, apoptosis, and cell cycle arrest. The pathophysiology of many cancer types has frequently been linked to polymorphisms in the TP53 locus. Over 200 single nucleotide polymorphisms (SNPs) have been identified in TP53. However, Pro72Arg (rs1042522) at codon 72, shows contradictory results in terms of cancer risk. In this study, we aimed to determine if the Pro72Arg (rs1042522) SNP in the TP53 gene would be linked to breast cancer (BC) risk among Egyptian patients.Materials and MethodsGenomic DNA was extracted from blood samples of 100 healthy volunteers and 100 breast cancer patients (50 familial and 50 non-familial). TP53 Genotyping was performed using tetra-primer amplification refractory mutation (Tetra-ARMS) PCR. Data were analyzed using SNPstat software.ResultsThe prevalence of TP53 (Pro72Arg) rs1042522 genotypes carrying the high-risk allele [Pro/Arg (CG) and Arg/Arg (GG)] were significantly higher in BC patients compared to healthy volunteers and were associated with BC susceptibility (OR 0.2; [95% CI 0.11–0.38]; P = 0.0001). However, there was no statistical significant difference in the prevalence of TP53 (Pro72Arg) rs1042522 genotypes carrying the high-risk allele between familial and non-familial BC patients. In addition, there was no association between the prevalence of TP53 (Pro72Arg) rs1042522 genotypes carrying the high-risk allele and BC patients’ clinical and pathological characteristics including tumor size, tumor grade, lymph node status, presence of lymphovascular invasion, expression of ER, PR and Her-2 in both of familial and non-familial BC patients.ConclusionsTP53 (Pro72Arg) rs1042522 is more prevalent among BC patients but not associated with disease progression.

Diagnostic and Prognostic Role of Serum Omentin and NGAL Levels in Egyptian Breast Cancer Patients.

Background Breast cancer (BC) is globally the main cause of cancer-related deaths in women. Tumor biomarkers have significant role in diagnosis and predicting the prognosis and decide the specific therapy to each patient. Aim In this study, we investigated whether omentin and NGAL levels were altered in patients with breast cancer and the relationship between these markers and their clinicopathological parameters. Subjects and Methods. This study included 120 patients with breast cancer and 30 healthy individuals served as controls. We measured the serum level of omentin and NGAL by ELISA technique. Results Our results showed that there were statistically significant differences in serum omentin and NGAL levels between two groups. Also, in breast cancer patients, there was significant difference between omentin level, the same results with NGAL level and patient's age, tumor size, lymph node, and metastasis. No significant relationship was found between omentin level and tumor grade, ER, PR, and HER2. The cutoff value for the prediction of breast cancer was determined at >113.2 ng/ml for omentin and >145.3 ng/ml for NGAL with a sensitivity of 91.7% and 100%, specificity of 100% and 80%, positive predictive value of 100% and 90.9%, negative predictive value of 85.7% and 100%, and accuracy of 94.4% and 93.3%, respectively. In conclusion, serum omentin and NGAL can be used as strong diagnostic markers for breast cancer.

MiR-34a and miR-21 as biomarkers in evaluating the response of chemo-radiotherapy in Egyptian breast cancer patients

BackgroundMiRNA-21 (miR-21) promotes the initiation and progression of tumor by initiating cell cycle differentiation, while miR-34a induces apoptosis through activating the tumor-suppressor gene p53, and by repressing the anti-apoptotic protein, B-cell lymphoma 2 (Bcl2). AimTo investigate if the expression folds change of circulating miR-21 and miR-34a could be a potential marker to evaluate the response of female breast cancer (BC) patients to the chemo-radiotherapy treatment. Subjectsand Methods: The study included 159 BC patients and 58 healthy females. Among patients’ 56 were Luminal A, 41 Luminal B, 15 Her-2/neu and 47 Basal like. Regarding stages, 118 BC patient were stage II, 12 stage I, and 29 stage III. Data of miR-21 and miR-34a were correlated with Bcl2, the breast cancer susceptibility genes BRCA1, and BRCA2, and p53. ResultsThe expression of miR-21 is upregulated (p < 0.001) in BC patients while miR-34a, is downregulated (p < 0.001), compared to control. The application of chemo-radiotherapy treatment decreased (p < 0.001) miR-21 and increased (p < 0.001) miR-34a. MiR-21 directly correlates with Bcl2 (p < 0.001) while miR-34a directly correlates with BRAC1, BRAC2 and p53 (p < 0.001).Conclusion: miR-34a and miR-21 may be considered as promising non-invasive biomarkers in evaluating the response of BC female patients to chemo-radiotherapy.

Mediterranean diet, BMI, healthy lifestyle, and social factors among a sample of Egyptian women with breast cancer

Background/aim Mediterranean diet is one of the healthy diets as many health benefits are strongly and robustly supported by evidence from long-term observational studies and randomized trials. This study aims to assess the nutrition-related breast cancer (BC) prevention factors, knowledge, attitudes, and practice of Egyptian BC patients. Patients and methods The study included 222 Egyptian women shared as volunteers in a case–control study, with age range: 25–75 years, with breast mass confirmed by mammogram. Using breast tissue core biopsy, 83 diagnosed with malignant tumor lesion, and 54 cases were found to have benign lesion. In total, 85 healthy women (control group) selection that was matched with the patients who had free mammograms on both sides, were chosen to be a control. All women were subjected to thorough clinical examination, anthropometric measurements, diet history, lifestyle, and health attitude assessment. Results Data revealed that benign and BC patients were older (49.33±11.98, 49.49±10.89 years), while BC patients had the highest BMI (35.45±15.58 kg/m2). Data concerned with successful social relationship were good; numerical differences between other factors that concerned lifestyle were reported. Large number of patients with benign tumors and BC did not adhere to consumed healthy diet, their scores when compared with Mediterranean diet were 5.58±3.70 and 5.44±2.81 compared with 6.67±3.00 of the control. BC patients had the lowest intake of milk and dairy products, vegetables, fruits, legumes, fish, and olive oil compared with the control with high significant differences (P≤0.01), while consumption of red and processed meat was significantly high, which was different from what was recorded in their belief and preference of such food. Conclusion According to the findings of this study, Egyptian BC patients who participated in this study had the lowest attitude and adherence to eat healthy diet. Data highlighted the necessity to increase the successful good social relationships and support for cancer patients.

Prevention of Adjuvant Treatment Induced Cardiotoxicity in Egyptian Breast Cancer (BC) Patients: A Randomized Prospective Study

Background: Adjuvant Anthracyclines Chemotherapy (ANTC) and trastuzumab have been documented to prolong survival in patients with breast cancer (BC). However, these drugs are also well known to induce left ventricular systolic dysfunction (LVSD). Multiple studies have shown that angiotensin converting enzyme inhibitors (ACEIs) and beta blockers (BBs) can prevent LVSD among women with BC.&#x0D; Objectives: We aimed to prospectively evaluate the efficacy of enalapril (ACEI) and carvedilol (BB) in preventing the ANTC ± trastuzumab induced LVSD, in patients with non-metastatic BC.&#x0D; Patients and Methods: We randomized 126 patients with non-metastatic (M0) BC, who were scheduled to be treated with ANTC ± trastuzumab into the intervention group (group 1; n = 63), which received enalapril and carvedilol or the control group (group 2; n = 63), which did not receive enalapril or carvedilol. To evaluate left ventricular (LV) systolic and diastolic functions the conventional echocardiography (ECHO) and cardiac magnetic resonance imaging (CMR) were performed at baseline, after 3 therapy cycles, and at 1-year follow-up. The secondary endpoint was designed to detect the incidence of a decrease in left ventricular ejection fraction (LVEF) ≥ 10%, heart failure (HF), LVSD (defined as LVEF&lt;45%) or deterioration in LV diastolic function.&#x0D; Results: In the intervention group, 58 patients had 3 cycles ANTC, 6 patients received 6 cycles ANTC, and 12 patients received trastuzumab. In the control group, 47 patients had 3 cycles ANTC, 16 patients were given 6 cycles ANTC and 18 patients received trastuzumab (as per the guidelines issued by breast clinic in the department of clinical oncology, faculty of medicine, Ain Shams University) for adjuvant and neoadjuvant chemotherapy in early breast cancer).&#x0D; After 3 ANTC cycles, LVEF did not change in the intervention group, but decreased by M-mode in the control group (p-value: 0.03), which was associated with statistically significant deterioration of LV diastolic function. At 1 year follow-up, while no change was observed in LVEF in group 1, there was a decrease in LVEF by CMR in group 2 (65.78% at baseline, 61.48% at 1 year; p-value: 0.04 8).&#x0D; Conclusion: Combined prophylaxis with enalapril and carvedilol may prevent LVSD in patients with non-metastatic BC treated with anthracycline-containing chemotherapy ± trastuzumab. However, the clinical relevance of this strategy should be confirmed in the future, large-scale randomized studies.

Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2–negative (p < 0.001), estrogen receptor–positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Mutational pattern of PIK3CA exon 20 in circulating DNA in breast cancer

Breast cancer (BC) is one of the most common cancers with diverse mutations, etiology and causes. Mutational signature of the driver genes could allow for better understanding disease etiology and progression. This study aims to assess PIK3CA Exon 20 somatic mutational signature in relation to potential underlying etiology. Circulating DNA of 71 Egyptian BC patients was isolated, amplified for PIK3CA Exon 20, and sequenced. Mutational signature was determined according to COSMIC v2 signature. Public BC dataset was analysed to assess PIK3CA mutations effect on the transcriptomic profile. Somatic mutations of PIK3CA exon 20 were found in 66.2% of the study cohort. Nucleotide substitution patterns were similar to general nucleotide substitution patterns in BC. Signature 3 and 9 were the most common signatures in the studied BC patients. Signature of Aristolochic acid exposure was found in some cases. The most common nucleotide substitution was T > A transversion, but substitutions T > G and T > C were correlated to each other and to the total mutation number. PIK3CA mutations were found to disrupt several pathways including RAC1, PDGF, Wnt, and integrin signalling. PIK3CA exon 20 mutational signatures in Egyptian BC patients could suggest a disease etiology involving homologous recombination deficiency (HRD) and polymerase eta (Pol η). Nucleotide substitution patterns could indicate the role of exposure to oxidative stress and some carcinogens such as 4-aminobiphenyl and Aristolochic acid.

Obesity in Terms of BMI and BSA in Egyptian Breast Cancer Patients: Can Tumor Behavior Be Predicted?

Background: Obesity is a major health problem worldwide and is involved in etiology of breast cancer. Egypt is ranked among the highest globally in obesity problem. Body mass index (BMI) is the most widely used tool to define obesity. Body surface area (BSA) is another measure used widely in clinical practice, particularly in calculating doses of chemotherapeutic agents. Both Body Surface Area (BSA) and Body Mass Index (BMI) rely on weight and height and can be used as indicators of obesity. Patients and Methods: This is a cross-sectional observational study that was carried out in the department of clinical oncology, Faculty of medicine, Ain Shams University Hospitals. Medical records of patients scheduled for adjuvant chemotherapy were revised regarding age, comorbidity, side of the tumor, stage, and type of the surgery performed. Immunohistochemistry (IHC) to detect ER, PR, and Her2 and molecular subtypes of the tumors was recorded. BMI and BSA were calculated for all patients. Inclusion Criteria: Female patients with newly diagnosed breast cancer, cases that didn’t start the adjuvant treatment, data for IHC available, weight, and height of the patients recorded in the files. Exclusion Criteria: Male breast cancer cases, bilateral cases, metastatic cases, age above 80 years, cases with multiple primaries. Results: The mean age of patients was 48 ± 11 years and 60% of them were premenopausal. The mean weight in Kgs was 81 ± 13 and the mean height in cm was 156 cm ± 5. Mean BMI was 33.8 ± 6.0 and mean BSA was 1.84 ± 0.15. Comorbidities were present in 10.6% of patients. In the studied group of patients, tumors were more common of right side (55.7%), T2 tumor (40%), N1 (40.9%), and stage III in 57.4%. Regarding the hormonal receptor status, most of the patients were ER+ (76.5%), PR+ (66.1%) and Her2? (73.9%). The molecular subtypes were also estimated with HR+ subtype most common in (60%) and Her2+ subtype least common in (10.4%). Neither BMI nor BSA was different based on menopausal status. Tumor characteristics were compared in relation to BMI and BSA, and none of the studied parameters regarding menopausal status, T staging, N staging, TNM staging, ER, PR, Her2 and molecular subtype were significantly associated with BMI or BSA. Receiver operating characteristic (ROC) curve was done for the poor prognostic variables. It was found that both BMI and BSA were poorly predictive for the prognostic tumor characteristics regarding T stage, N stage, Her2 overexpression and TN disease. Conclusion: Obesity is a major health problem among breast cancer patients in Egypt. Both BSA and BMI (as indicators of obesity) in Egyptian breast cancer patients are higher compared to other parts of the world. Both BMI and BSA were poorly predictive of prognostic parameters in breast cancer patients.

Cultural Adaptation and Validation of the EORTC QLQ-BR45 to Assess Health-Related Quality of Life of Breast Cancer Patients

Abstract Background The European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR23 is considered a premier module for breast cancer patients that is utilised synchronously with the core questionnaire. However, new and scalable treatments on breast cancer patients’ quality of life (QoL) need a more accurate and comprehensive tool to be assessed. Therefore, the EORTC introduced the newly updated module EORTC QLQ-BR45. Hence, the current study aims to perform cultural adaptation, pilot testing and assessment of the psychometric properties of the Egyptian Arabic translation of the EORTC QLQ-BR45 module on Egyptian breast cancer patients. Patients and Methods First, a review of the existing Arabic translation and the modified preliminary translation was sent to a professional proofreader. Then, comprehensibility of the Egyptian Arabic translation was pilot tested on a sample of 13 breast cancer patients. Afterwards, 74 patients with proven locally advanced breast cancer receiving neoadjuvant chemotherapy at Beni-Suef University Hospital, Beni-Suef, Egypt were interviewed. A second interview was conducted post-surgery for patients receiving target therapy, endocrine therapy or radiotherapy. The psychometric properties of the EORTC QLQ-BR45 were assessed in terms of reliability, convergent and divergent validity. Results Adequate internal consistency reliability (Cronbach’s α coefficients &gt;0.7) was demonstrated for the questionnaire, except for body image scale (α = 0.51) and systemic therapy side effects scale (α = 0.63). Multi-trait scaling analysis exhibited acceptable convergent and divergent validity, and scaling success was observed for all questionnaire items. Conclusion The Egyptian Arabic version of the EORTC QLQ-BR45 module is valid and adequately reliable. These results support using the EORTC QLQ-BR45 in future breast cancer clinical trials.

Adherence and Discontinuation of Endocrine Therapy among Egyptian Breast Cancer Patients Receiving Adjuvant Treatment: A Cross-sectional Study

Adherence and Discontinuation of Endocrine Therapy among Egyptian Breast Cancer Patients Receiving Adjuvant Treatment: A Cross-sectional Study

Abstract 257: Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing

Abstract Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing Aim: This study aimed to identify the tumor mutation burden (TMB) value in Egyptian Breast cancer (BC) patients. Additionally, we aimed to find the best model to predict TMB value by the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2), and proliferative index Ki-67, to help expecting the prognosis of patients and predicting the possible response to immunotherapy. Patients and methods: In 58 Egyptian patients with BC, the Ion AmpliSeq Comprehensive Cancer Panel based on NGS was used to determine the TMB value of primary tumor tissues of Egyptian BC patients. The predicted TMB value was divided into 4 groups: A (0.00-0.625), B (0.626-1.25), C (1.251-2.50), and D (&amp;gt;2.50), according to the quartile method, with group A as reference level. Different machine learning models were used to select the optimal classification model. Results: The measured TMB value was between 0 and 8.12/Mb. The TMB distribution among the studied 58 cases was: 19 cases in group A, 12 cases in group B, 14 cases in group C, and 13 cases in group D. ER positive expression was significantly associated with TMB ≤ 1.25 (ER positive vs ER-negative, OR =0.35, 95% CI: 0.04-2.98, p= 0.001). TMB ≤1.25 was significantly distributed in patients with PR positive expression (PR positive versus PR negative, OR = 0.17, 95% CI= 0.02-0.44, p= 0.002). Ki67 expression positive was significantly associated with TMB &amp;gt;1.25 than those who were Ki-67 expression negative (Ki67 positive versus Ki67 negative, OR = 9.33, 95% CI= 2.07-42.18, p= 0.004). Also, TMB &amp;gt;1.25 was significantly distributed in triple negative (TN) patients than non-TN patients (OR=9.69, 95% CI: 1.05-89.9, p=0.045). However, no significant differences were observed between HER2 positive and HER2 negative group (OR = 2.47, 95% CI: 0.64-9.54, p =0.19). The adjusted Pseudo-R2 was 0.329 (P&amp;lt;0.001). The optimized logistic regression model was TMB = -27.5 -1.82 ER - 0.73 PR + 0.826 HER2 + 2.08 Ki67. Conclusion: the preliminary findings of our studied sample set revealed that level of TMB in Egyptian BC patients is relatively low. Also, TMB value in hormone receptor positive and Ki-67 expression positive Egyptian BC patients is higher than hormone receptor negative and Ki-67 expression negative patients. Moreover, TMB value can be predicted based on the expression level of ER, PR, HER-2, and Ki-67. The optimized logistic regression model was TMB = -27.5 -1.82 ER - 0.73 PR + 0.826 HER2 + 2.08 Ki67. Citation Format: Auhood Nassar, Ahmed M. Lymona, Mai M. Lotfy, Amira Salah El-Din Youssef, Abdel-Rahman N. Zekri. Tumor mutation burden of Egyptian breast cancer patients based on next generation sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 257.