Different Stages Of Breast Cancer Research Articles

Complement protein expression changes in various conditions of breast cancer: in-silico analyses-experimental research.

Breast cancer is the most prevalent cancer diagnosed in females worldwide. The known biomarkers are insufficient to understand the actual prognosis of breast cancer, and identifying new biomarkers is desirable and valuable data to improve the patient's survival. Many inflammatory biomarkers, such as the complement system, can be regarded as prognostic values and as potent inflammatory mediators; complement proteins have a critical role in tumorigenesis. In the current study, the authors aim to investigate complement protein expression changes, particularly complement 3 (C3), complement 7 (C7), complement factor B (CFB), and complement factor D (CFD), in various conditions of breast cancer using in-silico tools. The intent data were extracted using webtools, including; Kaplan-Meier plotter, BcGenExMiner, UALCAN, cbioportal, GeneMania, and Enrichr. To select valid data, a P greater than 0.05 was considered. The current study clarified that 21 complement genes correlated to survival conditions. Also, down or upregulation of extracted genes and breast cancer statuses were identified. Additionally, expression level difference of complement genes in various breast cancer four stages was detected. Ultimately, co-expression genes with complement genes were extracted and networked. Changes in the expression of complement proteins can strongly correlate to breast cancer's prognosis, status, and survival. Furthermore, considering the vital role of CFD and CFB complement proteins in the alternative pathway in different stages of breast cancer, CFD and CFB can be regarded as reliable prognostic values for diagnosis.

Health-related quality of life in different stages of breast cancer in Serbia.

Breast cancer is the most commonly diagnosed malignant tumor worldwide, and Serbia ranks first in Europe in standardized breast cancer mortality rate. The aim of this research is to estimate health-related quality of life (HRQoL) and work productivity among patients in different stages of breast cancer in Serbia. A total of 175 breast cancer patients attending the breast cancer outpatient clinic at the Oncology Institute of Vojvodina between March 2022 and February 2023 were included in the study. Patients were divided into three mutually exclusive groups: (1) First year after primary breast cancer (Group P), (2) Second and following years after primary breast cancer or recurrence (Group S) and (3) Metastatic disease (Group M). The EQ-5D-3L self-classifier was used to estimate the HRQoL, using the EQ-5D-3L index value and visual analog scale (VAS) score. Мean EQ-5D-3L index value was 0.777 for Group P, and 0.768 for Group S. Patients with metastatic disease reported the lowest EQ-5D index value of 0.646 (p < 0.05). Pain/discomfort, as well as anxiety/depression, were the main drivers of the reduction in HRQoL. Patients in Group M also reported the lowest VAS score of 65.4. Furthermore, the highest percentage of women who sought leave or cited breast cancer as the reason for their early retirement were patients with metastatic disease. HRQoL was most impaired in Group M, and patients with metastatic disease were more likely to take sick leave or retire early due to breast cancer. Delaying or preventing metastatic recurrence could significantly benefit patients' productivity and HRQoL.

Effect of tumorspheres cultured from circulating cancer stem cells on the innate checkpoint CD47 in patients with breast cancer.

e13113 Background: Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies reported that increased expression of CD47 enable cancer cells to evade phagocytosis by macrophages and promote the cancer stem cell phenotype. Understanding the mechanisms behind this CD47 overexpression in cancer stem cells is critical for developing more effective immunotherapy. Therefore, in the current study, we evaluated the incidence and clinical relevance of tumorspheres cultured from cCSCs expressing CD47 in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of cCSCs was performed using the sphere-forming assay. Additionally, anti-CD47 antibody staining was applied to examine CD47 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres was associated with disease progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p&lt;0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p&lt;0.05). CD47 was highly expressed in tumorspheres, which are enriched from circulating cancer stem cells and associated with triple-negative tumors. We also observed high heterogeneity of CD47 expression between the tumorspheres of a patient and between the patients. Conclusions: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with high expression of CD47 might suggest their immunoregulatory potential. Better understanding of the interaction between cCSCs and tumor immunology may improve outcome especially in high-risk patients in part by attacking cCSCs and disinhibiting innate immunity.

A liquid biopsy-based assay for classifying breast cancer from benign nodule.

e12572 Background: Breast cancer (BRCA) ranks as the most frequently diagnosed non-skin cancer and stands as the second leading cause of cancer-related mortality in women in the United States. Globally, 2.3 million women were diagnosed with breast cancer in 2020, resulting in 685,000 deaths. Therefore, accurate classification of breast cancer could contribute to immediate treatment and improve outcomes for individuals diagnosed with breast cancer. Our study introduces an ensemble model utilizing the distinctive characteristics of cell-free DNA (cfDNA) fragmentation from whole genome sequencing (WGS) for the classification of BRCA and benign nodule. Methods: The study cohort consisted of 214 individuals diagnosed with breast cancer (BRCA) and 211 individuals with benign breast nodule. Employing whole-genome sequencing (WGS), we subjected plasma samples from all participants to comprehensive fragmentomic profiling. Three fragmentomic features: copy number variation (CNV), fragmentation size coverage (FSC), and fragmentation size distribution (FSD), were utilized by machine learning algorithms. An ensemble model integrated results from each algorithm then generated a cancer score ranging from 0 to 1 for each sample. The model was trained exclusively using the training cohort and the model’s performance was assessed in the independent validation cohort. Results: Our ensemble model demonstrated a sensitivity of 80.2% and a specificity of 95.3% in training cohort, with an AUC of 0.966. In the validation cohort, the model maintained its effectiveness, with a sensitivity of 73.6%, a specificity of 89.3% supported by an AUC of 0.919. Notably, the model showed various predictive ability across different stages of breast cancer. In the training cohort, it exhibited a sensitivity of 76.4% for Stage I, 81.8% for Stage II, and 88.9% for Stage III, indicating superior predictive power at advanced progression levels. Additionally, the model demonstrated a consistent sensitivity of 75% for Stage I in the validation cohort, affirming its reliable performance across independent datasets. When stratified by molecular subtypes, the model showed relatively lower scores and sensitivity BRCA with HR+/HER2+, compared to HR-/HER2+ and HR+/HER2- subgroups, as well as Triple-Negative Breast Cancer. Finally, the model generated unbiased predictions across various histology subtypes, accurately discerning ductal carcinoma and other BRCA histology subtypes in training and validation cohorts. Conclusions: The ensemble model that leverages non-invasive liquid biopsy-based assay for the accurate classification of BRCA and benign nodule provides a critical opportunity for effective intervention for cancer patients. This approach, facilitating swift and appropriate treatments, and optimizing the allocation of healthcare resources, underscores its significance in the ongoing pursuit of enhancing breast cancer care and outcomes.

Effectiveness of the socioecological informed contextual treatment summary and care plan (TSSCP-P, Brazil) for breast cancer survivors: a randomized, controlled study

ObjectiveThis study aimed to evaluate the impact of an intervention using the Treatment Summary and Survivorship Care Plan (TSSCP-P) on self-efficacy and quality of life (QoL) in breast cancer survivors.MethodA clinical study, randomized and controlled, conducted to assess self-efficacy and QOL in breast cancer survivors. The participants were randomly assigned to either an intervention group or a control group. The intervention group received individualized nursing consultations guided by the TSSCP-P, while the control group received standard care. Self-efficacy and QoL were assessed at three evaluation moments using validated scales: Functional Assessment of Cancer Therapy-Breast Plus Anm Morbidity (FACT B + 4) and Perceived General Self-Efficacy Scale. Statistical analyses, including regression analysis and hypothesis tests, were conducted to examine the effects of the intervention on self-efficacy and QoL.ResultsFemale breast cancer survivors (N = 101) were recruited. The intervention group demonstrated a significant improvement in self-efficacy over time compared to the control group (p = 0.01). However, no significant differences were observed in the overall QoL scores between the two groups. Subscale analysis revealed a significant improvement in physical well-being for the intervention group (p = 0.04), while emotional well-being showed a non-significant improvement (p = 0.07). The study suggests that individualized care plans and support strategies, such as the TSSCP-P, can positively influence breast cancer survivors’ self-efficacy and certain aspects of their QoL.ConclusionThese findings highlight the potential benefits of the TSSCP-P intervention in enhancing self-efficacy among breast cancer survivors. However, further research is needed to explore its impact on overall QoL and its effectiveness across different stages of breast cancer, as well as with longer follow-up periods.Clinical trial registration numberBrazilian Registry of Clinical Trials (ReBEC- RBR-2m7qkjy; UTN code: U1111-1257–3560), registered in April 19th, 2022.

Identification of Gene Expression in Different Stages of Breast Cancer with Machine Learning.

Determining the tumor origin in humans is vital in clinical applications of molecular diagnostics. Metastatic cancer is usually a very aggressive disease with limited diagnostic procedures, despite the fact that many protocols have been evaluated for their effectiveness in prognostication. Research has shown that dysregulation in miRNAs (a class of non-coding, regulatory RNAs) is remarkably involved in oncogenic conditions. This research paper aims to develop a machine learning model that processes an array of miRNAs in 1097 metastatic tissue samples from patients who suffered from various stages of breast cancer. The suggested machine learning model is fed with miRNA quantitative read count data taken from The Cancer Genome Atlas Data Repository. Two main feature-selection techniques have been used, mainly Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance, to identify the most discriminant and relevant miRNAs for their up-regulated and down-regulated states. These miRNAs are then validated as biological identifiers for each of the four cancer stages in breast tumors. Both machine learning algorithms yield performance scores that are significantly higher than the traditional fold-change approach, particularly in earlier stages of cancer, with Neighborhood Component Analysis and Minimum Redundancy Maximum Relevance achieving accuracy scores of up to 0.983 and 0.931, respectively, compared to 0.920 for the FC method. This study underscores the potential of advanced feature-selection methods in enhancing the accuracy of cancer stage identification, paving the way for improved diagnostic and therapeutic strategies in oncology.

Abstract PO1-13-09: Programmed cell death ligand 1 (PD-L1) is constitutively expressed on tumorspheres cultured from circulating cancer stem cells in breast cancer patients

Abstract Background Circulating cancer cells, and in particular their very rare subpopulation, circulating cancer stem cells (cCSCs), are responsible for recurrence and metastasis. The exact role of cCSCs in escape of cancer from immunosurveillance is still unknown, but recent studies revealed that enhanced PDL-1 expression in cancer stem cells is a novel mechanism to promoting cancer cell immune evasion and could crucially contribute to the maintenance of CSC self-renewal. Understanding the mechanisms behind this PDL-1 overexpression in cancer stem cells is critical for developing more effective anti-PD-1/PD-L1 therapy. Therefore the aim of the study was to determine the number of tumorspheres and expression of PD-L1 on tumorspheres cultured from cCSC in breast cancer patients. Methods: 110 patients with breast cancer in different stages of disease were included in this study. The determination of circulating cancer stem cells was performed using the sphere-forming assay. Additionally anti-PDL-1 antibody staining was applied to examine PDL-1 expression on breast tumorspheres. Results: We have developed an innovative in vitro platform for detection of cCSCs from peripheral blood of cancer patients. The number of tumorspheres increased significantly with tumor progression and aggressiveness of primary tumor. Patients with metastatic disease had statistically more tumorspheres as compared to patients without metastasis (30 vs 10/100µl blood, p&amp;lt; 0.05). Patients with multiple metastasis had more tumorspheres compared to patients with single metastases (60 vs 30/100µl blood, p&amp;lt; 0.05). The number of tumorspheres was positively correlated with Ki-67, Her2 status and grade score in primary breast tumors. We observed high PDL-1 expression and their considerable heterogeneity in enriched tumorspheres. Conclusion: The number of tumorspheres cultured from peripheral blood directly reflects aggressiveness and proliferation capacity of primary tumor. The presence of tumorspheres with expression of PDL-1 might suggest their immunomodulating potential. Better understanding of the interaction between cCSCs and tumor immunology may help to identify strategies to eradicate the minor subpopulation that escapes conventional therapy attack, thus providing a solution to the problem of drug resistance and metastasis. Citation Format: Monika PIZON, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. Programmed cell death ligand 1 (PD-L1) is constitutively expressed on tumorspheres cultured from circulating cancer stem cells in breast cancer patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-09.

Soluble Periostin is a potential surveillance biomarker for early and long-term response to chemotherapy in advanced breast cancer

BackgroundNoninvasive biomarkers for the assessment of response to chemotherapy in advanced breast cancer (BCa) are essential for optimized therapeutic decision-making. We evaluated the potential of soluble Periostin (POSTN) in circulation as a novel biomarker for chemotherapy efficacy monitoring.MethodsTwo hundred and thirty-one patients with different stages of BCa were included. Of those patients, 58 patients with inoperable metastatic disease receiving HER2-targeted or non-targeted chemotherapy were enrolled to assess the performances of markers in recapitulating the chemotherapy efficacy assessed by imaging. POSTN, together with CA153 or CEA at different time points (C0, C2, and C4) were determined.ResultsPOSTN levels were significantly associated with tumor volume (P < 0.0001) and TNM stages (P < 0.0001) of BCa. For early monitoring, dynamics of POSTN could recapitulate the chemotherapy efficacy among all molecular subtypes (Cohen’s weighted kappa = 0.638, P < 0.0001), much better than that of carcinoembryonic antigen (CEA) and cancer antigen 153 (CA15-3). For early partial response, superior performance of POSTN was observed (Cohen’s weighted kappa = 0.827, P < 0.0001) in cases with baseline levels above 17.19 ng/mL. For long-term monitoring, the POSTN response was observed to be strongly consistent with the course of the disease. Moreover, progression free survival analysis showed that patients experienced a significant early decrease of POSTN tended to obtain more benefits from the treatments.ConclusionsThe current study suggests that soluble POSTN is an informative serum biomarker to complement the current clinical approaches for early and long-term chemotherapy efficacy monitoring in advanced BCa.

Serum High Sensitivity C - reactive protein At Different Stages of Breast Cancer

Serum High Sensitivity C - reactive protein At Different Stages of Breast Cancer

Triglyceride-glucose index is a risk factor for breast cancer in China: a cross-sectional study

BackgroundThis research delved into the association between the risk of the Chinese population suffering from breast cancer (BC) and the triglyceride-glucose (TyG) index.MethodsA total of 2,111 sufferers with benign breast disease (BBD) and 477 sufferers with BC were enrolled, and their TyG index was measured. Participants with varying TyG index values were categorized into quartiles. Logistic regression analysis was employed to assess the relationship between the TyG index and BC risk. The diagnostic performance of the TyG index for different stages of BC was measured using the receiver operating characteristic (ROC) curve.ResultsThe TyG index of BC sufferers exceeded that of BBD (P < 0.001). A continuous increase in the risk of BC was found to be positively correlated with an ever-increasing TyG index. In the unadjusted model, the risk of getting BC mounted with quartiles of the TyG index growing (P < 0.001). In a logistic regression analysis that included all confounders, the highest quartile of the TyG index was strongly linked to BC risk [1.43 (1.01, 2.02), P < 0.05]. Moreover, with the adjustment of potential confounders, a high TyG index was found to result in a 2.53-fold higher risk of being diagnosed with advanced BC.ConclusionsThe risen TyG index was positively correlated to the heightening risk of BC and had the potential to serve as a promising biomarker for BC. Individuals with a high TyG index ought to be mindful of the heightened risk of BC onset and progression.

In-silico and in-vitro evidence suggest LINC01405 as a sponge for miR-29b and miR-497-5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma.

Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs. The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR-29b and miR-497-5p that results in regulating PI3-Kinase, WNT, and TGF-beta signaling pathways. We performed a meta-analysis of five GEO datasets, encompassing microarray and RNA-seq data, to identify differentially expressed genes. The Cancer Genome Atlas transcriptome dataset was also analyzed to determine essential gene modules, associated with different stages of breast cancer by weighted gene co-expression networks. In addition, networks of drug-gene interactions were constructed to explore potential treatment options. LINC01405 as a microRNA sponge was chosen and examined. furthermore, downstream target genes were discovered. Experimental validation consisted of plasmid constructs used in cell culture experiments, RT-qPCR for expression analysis, and cell cycle assays. Our bioinformatics findings showed higher LINC01405 expression in Basal-like triple-negative breast carcinoma. In contrast, lower expression in Luminal samples was observed compared with normal samples, which was consistently observed in both breast cancer tissues and cell lines. LINC01405 expression level was correlated with miR-29b and miR-497 levels. The MDA-MB-231 cell line demonstrated higher LINC01405 expression and lower miR-29b and miR-497 expression levels. However, SKBR3 and MCF7 cells had lower LINC01405 expression and higher miR-29b and miR-497 levels, suggesting a regulatory role for LINC01405 as a competing endogenous RNA. This was experimentally confirmed when LINC01405 was overexpressed in SKBR3 cells, and the common target genes of miR-29b and miR-497 were upregulated. Additionally, LINC01405 upregulation led to the increased cell populations, proliferation, and upregulation of critical cancer-related genes, including AKT1, AKT3, mTOR, WNT3A, SMAD3, CYCLIN D1, CYCLIN D2, BCL2, and GSK3B. We revealed the differential expression of LINC01405 in several types of breast cancer and its role in regulating signaling pathways, potentially via scavenging miRNAs. These findings clarified the role of LINC01405 in breast cancer development and identified potential therapeutic targets.

DNA Gate-Based CRISPR-Cas Exponential Amplification System for Ultrasensitive Small Extracellular Vesicle Detection to Enhance Breast Cancer Diagnosis.

Tumor-derived small extracellular vesicles (tEVs) as potential biomarkers possess abundant surface proteins closely related to parent cells, which are crucial for noninvasive cancer diagnosis. However, tEVs exhibit phenotype heterogeneity and low abundance, posing a significant challenge for multiplex detection with a high sensitivity. Herein, we developed a DNA gate-based exponential amplification CRISPR-Cas (DGEAC) system for accurate and ultrasensitive detection of tEVs, which can greatly improve the accuracy of breast cancer (BC) diagnosis. Based on the coexpression of CD63 and vascular endothelial growth factor (VEGF) on BC-derived tEVs, we developed a dual-aptamer-based AND gate fluorescent probe by proximity hybridization. By integrating the target recognition and trans-cleavage activity of Cas12a, an autocatalysis-driven exponential amplification circuit was developed for ultrasensitive detection of CD63 and VEGF proteins on tEVs, which could avoid false negative signals from single protein or other interfering proteins. We achieved highly sensitive detection of tEVs over a linear range from 1.75 × 103 to 3.5 × 108 particles/mL with a detection limit as low as 1.02 × 103 particles/mL. Furthermore, the DGEAC system can distinguish tEVs from tEVs derived from different BC cell lines, including MDA-MB-231, MCF-7, SKBR3, and MCF-10A. Compared to linear amplification (AUC 90.0%), the DGEAC system effectively differentiates BC in different stages (AUC 98.3%).

Comparison of BRCA1 Gene Expression and CA15‐3 Tumor Marker Level in Different Stages of Breast Cancer

Breast cancer (BC), a globally prevalent malignancy, shows significant variability in incidence across different geographical regions. In this study, we examined the expression of the tumor suppressor gene BRCA1 and the tumor marker CA15‐3 in women diagnosed with BC, focusing on different cancer grades. Our research, conducted at the Baqiyat Elah Hospital in Tehran in 2021, involved collecting blood and serum samples from BC patients. These samples underwent BRCA1 gene expression analysis and CA15‐3 tumor marker assessment. Using the AJCC grading system, we categorized BC patients into various grades. Our findings revealed that BRCA1 gene expression was present in 28.57% of patients, while 71.43% showed negative expression. Both BRCA1 expression and CA15‐3 levels significantly increased with advanced cancer stages (P &lt; 0.001). These results suggest the potential utility of BRCA1 gene expression and CA15‐3 tumor marker assessment in BC prognosis and management, particularly concerning staging and disease progression. This study provides valuable insights into the biology of BC and the development of prognostic markers for improved patient outcomes.

Beyond Blood Counts: Hematocrit Dynamics in Breast Cancer Monitoring

This review delves into the expanding role of hematocrit dynamics as a critical parameter in the monitoring and management of breast cancer. Moving beyond conventional reliance on blood counts, the analysis explores the intricate relationship between hematocrit fluctuations and various facets of breast cancer progression, treatment response, and overall patient outcomes. The review aims to elucidate the potential of hematocrit as a dynamic biomarker, offering insights into the underlying physiological changes associated with the disease. By examining the correlation between hematocrit levels and different stages of breast cancer, treatment modalities, and patient-specific factors, this review seeks to enhance the current understanding of hematocrit's prognostic and predictive value. Additionally, it explores the implications of hematocrit dynamics on therapeutic strategies, emphasizing the need for personalized approaches in breast cancer care. The synthesis of available evidence in this review underscores the significance of considering hematocrit as a valuable and dynamic parameter in breast cancer monitoring. The integration of hematocrit dynamics into clinical practice has the potential to refine diagnostic and prognostic frameworks, contributing to a more comprehensive and personalized approach to breast cancer management. In conclusion, this review provides a critical examination of the evolving landscape beyond blood counts, highlighting the emerging importance of hematocrit dynamics in enhancing our understanding and management of breast cancer.

Construction of an Emotional Lexicon of Patients With Breast Cancer: Development and Sentiment Analysis.

The innovative method of sentiment analysis based on an emotional lexicon shows prominent advantages in capturing emotional information, such as individual attitudes, experiences, and needs, which provides a new perspective and method for emotion recognition and management for patients with breast cancer (BC). However, at present, sentiment analysis in the field of BC is limited, and there is no emotional lexicon for this field. Therefore, it is necessary to construct an emotional lexicon that conforms to the characteristics of patients with BC so as to provide a new tool for accurate identification and analysis of the patients' emotions and a new method for their personalized emotion management. This study aimed to construct an emotional lexicon of patients with BC. Emotional words were obtained by merging the words in 2 general sentiment lexicons, the Chinese Linguistic Inquiry and Word Count (C-LIWC) and HowNet, and the words in text corpora acquired from patients with BC via Weibo, semistructured interviews, and expressive writing. The lexicon was constructed using manual annotation and classification under the guidance of Russell's valence-arousal space. Ekman's basic emotional categories, Lazarus' cognitive appraisal theory of emotion, and a qualitative text analysis based on the text corpora of patients with BC were combined to determine the fine-grained emotional categories of the lexicon we constructed. Precision, recall, and the F1-score were used to evaluate the lexicon's performance. The text corpora collected from patients in different stages of BC included 150 written materials, 17 interviews, and 6689 original posts and comments from Weibo, with a total of 1,923,593 Chinese characters. The emotional lexicon of patients with BC contained 9357 words and covered 8 fine-grained emotional categories: joy, anger, sadness, fear, disgust, surprise, somatic symptoms, and BC terminology. Experimental results showed that precision, recall, and the F1-score of positive emotional words were 98.42%, 99.73%, and 99.07%, respectively, and those of negative emotional words were 99.73%, 98.38%, and 99.05%, respectively, which all significantly outperformed the C-LIWC and HowNet. The emotional lexicon with fine-grained emotional categories conforms to the characteristics of patients with BC. Its performance related to identifying and classifying domain-specific emotional words in BC is better compared to the C-LIWC and HowNet. This lexicon not only provides a new tool for sentiment analysis in the field of BC but also provides a new perspective for recognizing the specific emotional state and needs of patients with BC and formulating tailored emotional management plans.

Comparison of seroma formation between flap and non-flap fixation technique of mastectomy for different stages of breast cancer.

Objective: To compare the effect of flap fixation and non-flap fixation for preventing seroma formation depending upon stage of surgery in patients undergoing mastectomy at RMU Allied Hospitals following mastectomy in our local population. Study Design: Randomized Controlled Trial. Setting: Surgical Units of Holy Family Hospital, Benazir Bhutto Hospital, DHQ Hospital (RMU &amp; Allied Hospital). Period: October 2020 to April 2021. Material &amp; Methods: Sample size of 114 cases was included in the study. It was Non probability, consecutive sampling technique. Patients were equally randomized to flap-fixation (Group A) and non-flap fixation (Group B). Patients of both groups were followed up to 48 hours postoperatively for seroma formation. Results were analysed using SPSS software and compared by applying chi-square test and p-value ≤0.05 considered significant. Results: Statistically significant difference (p-value ≤0.05) for seroma formation was noted only in disease stage IIIA. In group A (Flap Fixation), seroma formation was noted in 22.8% (n=13) patients, while in group B (Non-Flap Fixation) it was noted in 45.6% (n=26) patients only. Conclusion: The patients with stage IIIA undergoing mastectomy are significantly (p-value ≤0.05) associated with seroma formation. Whereas, flap fixation is more useful technique for minimizing seroma formation.

A review of FDA approved drugs and their formulations for the treatment of breast cancer.

Breast cancer is one of the most diagnosed solid cancers globally. Extensive research has been going on for decades to meet the challenges of treating solid tumors with selective compounds. This article aims to summarize the therapeutic agents which are either being used or are currently under approval for use in the treatment or mitigation of breast cancer by the US FDA, to date. A structured search of bibliographic databases for previously published peer-reviewed research papers on registered molecules was explored and data was sorted in terms of various categories of drugs used in first line/adjuvant therapy for different stages of breast cancer. We included more than 300 peer-reviewed papers, including both research and reviews articles, in order to provide readers an useful comprehensive information. A list of 39 drugs are discussed along with their current status, dose protocols, mechanism of action, pharmacokinetics, possible side effects, and marketed formulations. Another interesting aspect of the article included focusing on novel formulations of these drugs which are currently in clinical trials or in the process of approval. This exhaustive review thus shall be a one-stop solution for researchers who are working in the areas of formulation development for these drugs.

The role of circulating cell-free DNA and its integrity as a biomarker for diagnosis of breast cancer using ALU (247/115) bP sequences

of breast cancer by using sensitive and specific biomarkers is necessary. Cell– free DNA (cf-DNA) is a candidate biomarker in various cancers. Contrasting, shorted uniformed DNA released from apoptotic non-diseased cells, DNA released from malignant cells varies in size. DNA integrity is a ratio between 247 and 115 bp. This study aimed to evaluate the diagnostic values of cf-DNA using ALU -247 and ALU- 115 and DNA integrity in peripheral blood of breast cancer patients as a noninvasive marker. Also, to determine correlations between ALU-247 and ALU-115, DNA integrity, cancer antigen (CA )15-3 and carcinoembryonic antigen (CEA) with each other in breast cancer patients and in different stages of breast cancer. This study included 100 females, divided into 3 groups. The first group consisted of 20 apparently healthy females as the control group. The second group included 20 patients with benign breast lesions. The third group included 60 patients with breast cancer. Serum levels of both ALU-247 and ALU-115 as well as cf-DNA integrity were statistically significant higher in breast cancer patients as compared to the control group (p=0.018, p&lt;0.001 and p=0.009 respectively). Compared to the control group, ALU-247 had the best diagnostic sensitivity for diagnosis of breast cancer (86.78%) with 75% specificity with area under the curve of 0.848. We concluded that measuring ALU-247, ALU-115 and DNA integrity in peripheral blood would be a promising novel approach for diagnosis and early detection of breast cancer.

Identification, characterization, and prognosis investigation of pivotal genes shared in different stages of breast cancer

One of the leading causes of death (20.1 per 100,000 women per year), breast cancer is the most prevalent cancer in females. Statistically, 95% of breast cancer are categorized as adenocarcinomas, and 55% of all patients may go into invasive phases; however, it can be successfully treated in approximately 70–80% of cases if diagnosed in the nascent stages. The emergence of breast tumor cells which are intensely resistant to conventional therapies, along with the high rate of metastasis occurrence, has highlighted the importance of finding novel strategies and treatments. One of the most advantageous schemes to alleviate this complication is to identify the common differentially expressed genes (DEGs) among primary and metastatic cancerous cells to use resultants for designing new therapeutic agents which are able to target both primary and metastatic breast tumor cells. In this study, the gene expression dataset with accession number GSE55715 was analyzed containing two primary tumor samples, three bone-metastatic samples, and three normal samples to distinguish the up- and down regulated genes in each stage compared to normal cells as control. In the next step, the common upregulated genes between the two experimental groups were detected by Venny online tool. Moreover, gene ontology, functions and pathways, gene-targeting microRNA, and influential metabolites were determined using EnrichR 2021 GO, KEGG pathways miRTarbase 2017, and HMDB 2021, respectively. Furthermore, elicited from STRING protein–protein interaction networks were imported to Cytoscape software to identify the hub genes. Then, identified hub genes were checked to validate the study using oncological databases. The results of the present article disclosed 1263 critical common DEGs (573 upregulated + 690 downregulated), including 35 hub genes that can be broadly used as new targets for cancer treatment and as biomarkers for cancer detection by evaluation of expression level. Besides, this study opens a new horizon to reveal unknown aspects of cancer signaling pathways by providing raw data evoked from in silico experiments. This study’s outcomes can also be widely utilized in further lab research since it contains diverse information on common DEGs of varied stages and metastases of breast cancer, their functions, structures, interactions, and associations.

Clinical significance of long non-coding RNA ZEB2-AS1 and EMT-related markers in ductal and lobular breast cancer.

Breast cancer is considered the most prevalent type of cancer in women and accounts for a high rate of death. A body of research has demonstrated that lncRNAs have a regulatory function in human diseases, especially cancers. ZEB2-AS1 is known as an oncogenic lncRNA in various types of cancers, and its deregulation may contribute to cancer development and progression. Therefore, we aimed to reveal the association of ZEB2-AS1 expression with epithelial-mesenchymal transition (EMT) markers, as a hallmark of cancer progression, in a clinical setting. A recent study suggested that ZEB2-AS1 is significantly involved in EMT. Here we intended to explore the roles of lncRNA ZEB2-AS1 in breast cancer (BC) using bioinformatics tools and laboratory settings. We first evaluated the expression of ZEB2-AS1 mRNA in tumor and healthy control tissues by lnCAR database. Furthermore, ZEB2-AS1 expression level, ZEB2, E-cadherin, and vimentin was measured via qRT-PCR in 30 paired ductal and lobular carcinoma tissues from breast cancer patients and the normal adjacent ones. The correlation between the lncRNA ZEB2-AS1 expression and clinicopathological characteristics of the breast cancer patients was evaluated. ZEB2-AS1 showed an upregulation in breast cancer tissues (p = .04) compared to normal adjacent samples. In addition, its level was higher in breast cancer patients with advanced Stages (III & IV) (n = 18) compared to early Stages (I & II) (n = 12) (p = .04). Moreover, ZEB2 (p = .01) and vimentin (p = .02) expression were upregulated in the BC sample, but the expression level of E-cadherin (p = .02) was downregulated when compared with the adjacent normal tissues. By comparison of the expression of EMT-markers between different stages of breast cancer, overexpression of ZEB2 (p = .04) and vimentin (p = .04) and down expression of E-cadherin (p = .03) was observed in advance stages. Collectively, our findings suggest that ZEB2-AS1 expression is significantly upregulated in tumor tissues, especially in advanced stages and ZEB2-AS1 is associated with the aggressiveness of tumors by functioning as putative oncogenic lncRNA. In addition, a combination of ZEB2-AS1 and these EMT markers in breast cancer potentiates these genes as biomarkers for tumor progression.