Different Stages Of Breast Cancer Research Articles

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.

Evaluation of role of serum prolactin & ki-67 in different stages of breast cancer

Breast cancer is the most frequent cancer among women. Prolactin (PRL) is a hormone secreted from anterior pituitary gland which stimulates cell proliferation, survival of cancer cells, its migration, invasion and angiogenesis. Breast cancer is strongly associated with raised plasma Prolactin level (PRL). The Prolactin behaves like Growth Hormone and its actions by the growth-promoting JAK/STAT pathway suggests its tumor-promoting effects.Ki-67 a Nuclear Protein is highest in Luminal B, Ki67 are not related to age but is correlated with tumor size. Fraction of Ki-67 positive tumor cells correlates with the clinical course of cancer cells. Hence, Ki- 67 can be an effective target in cancer therapy. Ki-67% and Serum Prolactin level may be considered a valuable biomarker in breast cancer patients and be used in treatment, follow-up and Prognosis.

Clinicopathologic Features of Breast Cancer in Egypt-Contemporary Profile and Future Needs: A Systematic Review and Meta-Analysis.

Breast cancer (BC) is the most common cancer among Egyptian females. No current national cancer database is available in Egypt to provide reliable data on the specific clinicopathologic features of BC in this population. Herein, we investigated the clinical profile of BC among Egyptian women. A systematic review of studies on BC published from inception until December 2021 was performed. We explored pooled estimated proportions of different stages of BC at presentation in Egypt and other clinicopathologic features including age, menopausal status, tumor (T) and lymph node (N) stages, and biological subtypes. Data analysis was performed using meta package (R). Twenty-six studies were eligible for our systematic review and meta-analysis, including 31,172 BC cases. In 12 studies, including 15,067 patients with BC, the estimated mean age was 50.46 years (95% CI, 48.7 to 52.1; I2, 99%), with a pooled proportion of premenopausal/perimenopausal women of 57% (95% CI, 50 to 63; I2, 98%). Among 9,738 patients with BC, pooled proportions of stage I, II, III, and IV were 6% (95% CI, 4 to 8; I2, 90%), 37% (95% CI, 31 to 43; I2, 93%), 45% (95% CI, 42 to 49; I2, 78%), and 11% (95% CI, 9 to 15; I2, 87%), respectively. The pooled proportions of patients with T3 and T4 tumors were 21% (95% CI, 14 to 31; I2, 99%) and 8% (95% CI, 5 to 12; I2, 96%), respectively, while those with positive lymph nodes were 70% (95% CI, 59 to 79; I2, 99%). Dominance of advanced stage and young age at diagnosis represented the two main features of BC among Egyptian women. Our data may serve to guide the policymakers in Egypt as well as other countries with lower resources to prioritize the diagnostic and therapeutic needs in this context.

Proteoglycans in breast cancer, identification and characterization by LC-MS/MS assisted proteomics approach: A review.

Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC-MS/MS-based proteomics approach, which will be further helpful for identification of potential PGs-based biomarkers or therapeutic targets. There is a lack of comprehensive knowledge on the use of LC-MS/MS-based proteomics approaches to identify and characterize PGs in breast cancer. LC-MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach. Proteomics techniques including LC-MS/MS-based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC-MS/MS-based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers.

Incidence of second primary malignancies in women with different stages of breast cancer.

Breast cancer (BC) is the most common cancer in women worldwide. Because of the extended survival of patients with BC, the occurrence of second primary malignancies (SPMs) after BC is an important issue. We identified female patients with BC in the Breast Cancer Health Database of Taiwan, which includes four cancer registry datasets between 2002 and 2014 from Taiwan Cancer Registry. We compared the incidence of SPM between patients who received chemotherapy and/or radiotherapy with those who did not. Stratified analyses were performed according to the American Joint Committee on Cancer (AJCC) stage. The Cox regression model was used to identify the risk factors for SPM and evaluate their effects. We enrolled 85,947 eligible patients with BC, and 2,656 (3.09%) patients developed SPM. The median duration of SPM was 2.70 (1.14-5.14) years. Radiotherapy was administered in 40,946 (47.64%) patients, and chemotherapy was administered in 52,120 (60.64%). The most common SPMs were digestive tract cancers (876, 31.89%). The risk factors for SPM included the AJCC stage, chemotherapy, radiotherapy, age, and underlying comorbidities. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in any stage. In contrast, after adjusting for other risk factors, patients at stage III/IV who received both therapies had lower risks of SPM compared with those who did not (p = 0.047). The risk of SPM was different across BC stages. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in women with BC.

Downregulation of MICA/B tumor surface expressions and augmented soluble MICA serum levels correlate with disease stage in breast cancer.

In this study, the profiling of the expression of major histocompatibility complex (MHC) class I-related chain A and B (MICA/B) in human breast cancer tumor tissue, saliva, and urine samples of breast cancer patients and control is carried out. MICA/B is ligand of NKG2D receptor expressed on malignant cells. The release of MICA/B from tumor tissue comprises an immune escape mechanism that impairs antitumor immunity. Based on this literature we explored the potential of soluble MICA (sMICA) as a marker in breast cancer (BC). The expression was profiled by using immunohistochemistry (MICA/B), western blot (MICA/B) and ELISA (MICA). The optical density of western blot of MICA/B in different stages of BC illustrated significant difference as per one way analysis of variance and significant difference with stage III and IV by Dunnett's multiple comparisons test respectively. Analysis of sMICA in serum, saliva and urine of BC patients revealed significantly higher levels (median 41.0 ± 4.1 pg/ml in pre-treatment sera, 181.9 ± 1.6 pg/ml in saliva and 90.7 ± 1.7 pg/ml in urine) than in control (median <1.2 pg/ml). The elevated levels of sMICA were related to the cancer stage. The elevated levels of sMICA were observed in patients with well differentiated cancer while the poor expression of sMICA was observed in patients with poorly differentiated tumors. Tumor immunity is impaired by the release of MICA in the biofluids and may be useful for detection and diagnosis of the stage of BC.

Correlation between oxidative stress markers and cytokines in different stages of breast cancer.

This study aims to estimate the level of malondialdehyde (MDA) as oxidative stress marker and reduced glutathione (GSH) as antioxidant and correlate them to different inflammatory markers as interleukins (IL-6, IL-8, IL-10) and tumor necrosis factor alpha (TNF-α) in different stages of breast cancer (BC). For the purpose of comparisons, 35 healthy subjects matched for age, sex and ethnic background were selected who have no history or clinical evidence of BC or any chronic disease and obvious abnormalities as a control group and 35 patients of different stages of BC were participated in the study. The cancer patients were diagnosed by specialists. Even the exact cause of the disease has not been identified but according to this study, 5% of the patients were having family history of the disease and 62% of the patients were having a BMI over 25. Over 60% of the patients were postmenopausal and all females participated in this study were nonsmokers. MDA level showed a significant increase when BC patients were compared to healthy subjects, this oxidative stress marker showed a significant increase with the increase of the stage of the disease. In contrast the level of the lipid peroxide scavenger GSH reduced with increasing the stage of the disease. The level of some cytokines showed a significant change between different stages and the control group. Correlation between MDA and GSH with these cytokines showed a positive correlation between all cytokines and the MDA level and a negative correlation between GSH and the cytokines. The results of this study suggests that BC stimulates the oxidative stress response and for that, different inflammatory cytokines will be produced and there is a pronounced relationship between oxidative stress parameters and these cytokines and the level of these cytokines are associated with aggressive tumors.

Roles of Different Radiations in Treatment of Breast Cancer

The review aimed to describe the role of radiations in treatment of breast cancer. The review also describe that which type of radiation is used to treat different stages of breast cancer i.e, metastatic stage, advance stage and early stage of breast cancer. The radiation therapy plays a significant role in the treatment of breast cancer. The treatment delivery methods are considerably changed in the recent decades. The concept of using radiotherapy for the treatment of breast cancer has remained equally important for oncologists throughout the years still research has been going on to make these radiotherapy sessions more and more convenient for the patients. The combination of breast conservation surgery an APBI can result in survival without having any other health related issues for other nearby organs. Recent findings have reported about incorporation of APBI into clinical usage. APBI should be used for patients with low risk of ductal carcinoma or in case of first stage of invasive ductal cancer which has prominent margins for the excision, and where the estrogen receptor positivity is clear. Radiation therapy is effectively used for the treatment and management of loco regionally advanced and distant metastatic disease. There is research going on to find most appropriate technique in which convenient and protected procedure is used for patients to avoid any side effects. New and advanced techniques are used to limit radiation related toxicity.

The content of cytokines in the blood of patients with various stages of breast cancer

Background. Cytokine homeostasis is an important factor characterizing the general condition and adaptive capabilities of the body of patients with malignant neoplasms. However, the role of various growth factors and their significance in the development and enhancement of malignant growth in breast cancer remain poorly understood.&#x0D; Aim. To evaluate the levels of cytokines - tumor necrosis factor , interleukins-4, -6, -8 and -10 in the blood serum of patients with different stages of breast cancer in comparison with healthy volunteers.&#x0D; Material and methods. The study was conducted in 65 patients aged 25 to 67 years (mean age 44.5 [40.056.5] years). Two groups were distinguished: the first with stage 12, the second with stage 34 of breast cancer. The comparison group consisted of 15 apparently healthy women without cancer, aged 29 to 66 years (mean age 51.0 [39.061.0] years). Blood levels of tumor necrosis factor , interleukins-4, -6, -8 and -10 were studied by enzyme immunoassay. The obtained data were processed using the methods of variation statistics, the Statistica 10.0 software package. The significance of differences was assessed by calculating the median and interquartile interval, analysis of variance was performed using the KruskalWallis H-test, and Dan's Q-test was used for multiple comparisons. The critical significance level p for statistical tests was taken equal to 0.05.&#x0D; Results. In the group of patients with stage 12 breast cancer, an increase in the blood levels of all studied cytokines was revealed in comparison with the group of healthy women: interleukin-6 (p=0.00719), interleukin-8 (p=0.00259), tumor necrosis factor (p=0.00014), interleukin-4 (p1=0.0133), interleukin-10 (p1 0.00001). In the group of patients with stage 34 breast cancer, an increase in blood levels was characteristic of all studied cytokines: interleukin-8 (p=0.00009), tumor necrosis factor (p=0.000004), interleukin-4 (p 0.00001), interleukin-10 (p 0.00001), except for interleukin-6 (p=0.15608). The established patterns in changes in the content of cytokines in the blood of patients with breast cancer at different stages of development can serve as the basis for developing approaches to the diagnosis and treatment of the disease.&#x0D; Conclusion. In patients with breast cancer, the levels of tumor necrosis factor , interleukins-4, -6, -8, -10 (p 0.05) are higher than in healthy women.

Whole-genome circulating tumor DNA methylation landscape reveals sensitive biomarkers of breast cancer.

The changes in circulating tumor DNA (ctDNA) methylation are believed to be early events in breast cancer initiation, which makes them suitable as promising biomarkers for early diagnosis. However, applying ctDNA in breast cancer early diagnosis remains highly challenging due to the contamination of background DNA from blood and low DNA methylation signals. Here, we report an improved way to extract ctDNA, reduce background contamination, and build a whole‐genome bisulfite sequencing (WGBS) library from different stages of breast cancer. We first compared the DNA methylation data of 74 breast cancer patients with those of seven normal controls to screen candidate methylation CpG site biomarkers for breast cancer diagnosis. The obtained 26 candidate ctDNA methylation biomarkers produced high accuracy in breast cancer patients (area under the curve [AUC] = 0.889; sensitivity: 100%; specificity: 75%). Furthermore, we revealed potential ctDNA methylated CpG sites for detecting early‐stage breast cancer (AUC = 0.783; sensitivity: 93.44%; specificity: 50%). In addition, different subtypes of breast cancer could be well distinguished by the ctDNA methylome, which was obtained through our improved ctDNA‐WGBS method. Overall, we identified high specificity and sensitivity breast cancer‐specific methylation CpG site biomarkers, and they will be expected to have the potential to be translated to clinical practice.

Assessing the interrelation between oestrogen receptor status, heart rate variability and serum nitric oxide in breast cancer patients: Understanding their prognostic relevance.

e12564 Background: Heart Rate Variability (HRV) is a non-invasive procedure to assess cardiac functions and provides an index of autonomic function that intricately controls vascular tone. Studying the alteration in HRV with agents producing oxidative stress will provide useful information about disease progression. Lower HRV indicates low level of Parasympathetic Nervous System activation and dysregulation of cardiac functions. Elements of tumour microenvironment like prostaglandin E2, oestrogen and hypoxia stimulate nitric oxide (NO) production which reacts with free radicals released by tumour tissue forming oxidising agents. NO enhances oxidative stress causing vascular dysfunction. Very few studies have reported an interrelationship between NO and HRV parameters in breast cancer. The aim of the study is to verify the relation between HRV and serum NO levels in ER+ and ER- breast cancer groups. Methods: Study design: Analytical, Cross sectional. Sample Size: 135 women above 20 years of age with and without breast cancer. 69 women with histologically proven breast cancer in different stages and 66 women who were healthy age matched controls were included. Oestrogen Receptor (ER) status was obtained from clinical records. Out of 69 women with breast cancer, 31 were ER- with 15 in stage 1 and 16 in stage 2. 38 women were ER+ with 5 in stage 2 and 33 in stage 3. Serum NO was measured using colorimetry. Heart Rate Variability was measured from lead II ECG using Power Lab 15T and lab chart software. Serum NO levels and HRV parameters were compared between ER groups. Results: ER+ women had higher HRV with parasympathetic predominance compared to ER- with p&lt;0.001. ER+ women also had higher serum NO levels compared to ER- group with p&lt;0.001. Though no direct correlation was noticed between NO and HRV, multiple analysis of variance showed significant (p&lt;0.001) difference of all values across the groups. irrespective of menopausal status. Conclusions: A significant difference was observed in HRV of ER+ and ER- women with breast cancer. Most ER+ women were in stage 3 with significantly higher NO levels. Serum NO is expected to be the factor most responsible for HRV changes particularly in stage 3/ER+. Parasympathetic predominance seen in ER+ women possibly is due to high NO levels.[Table: see text]

PD-L1 is overexpressed on tumorspheres cultured from circulating cancer stem cells in patients with breast cancer.

3052 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 linked to 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 &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). 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. Conclusions: 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 immunregulatory 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.

Multi-Omics Approach Points to the Importance of Oxylipins Metabolism in Early-Stage Breast Cancer.

Simple SummaryOn a system level, multi-omics approaches allow studying oxylipins, metabolites of omega-3 or omega-6 polyunsaturated fatty acids. We compared the ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) oxylipin profile signatures in the blood plasma of 152 healthy volunteers (HC) and 169 patients with different stages of breast cancer (BC). We identified 18 differentially expressed oxylipins between BC vs. HC patients, including anandamide, prostaglandins, and hydroxydocosahexaenoic acids. To integrate lipidomics, transcriptomics, and genomics data, we analyzed a transcriptome of 10 open database datasets obtained from tissues and blood cells of BC patients and SNP data for 33 genes related to oxylipin metabolism and revealed 19 changed genes, among them CYP2C19, PTGS2, HPGD, and FAAH included in the list of DEGs in the analysis of transcriptomes and the list of SNPs associated with BC. Our data allow us to suppose that oxylipin profiles can be used to evaluate the early stages of breast cancer.The involvement of oxylipins, metabolites of polyunsaturated fatty acids, in cancer pathogenesis was known long ago, but only the development of the high-throughput methods get the opportunity to study oxylipins on a system level. The study aimed to elucidate alterations in oxylipin metabolism as characteristics of breast cancer patients. We compared the ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) oxylipin profile signatures in the blood plasma of 152 healthy volunteers (HC) and 169 patients with different stages of breast cancer (BC). To integrate lipidomics, transcriptomics, and genomics data, we analyzed a transcriptome of 10 open database datasets obtained from tissues and blood cells of BC patients and SNP data for 33 genes related to oxylipin metabolism. We identified 18 oxylipins, metabolites of omega-3 or omega-6 polyunsaturated fatty acids, that were differentially expressed between BCvsHC patients, including anandamide, prostaglandins and hydroxydocosahexaenoic acids. DEGs analysis of tissue and blood samples from BC patients revealed that 19 genes for oxylipin biosynthesis change their expression level, with CYP2C19, PTGS2, HPGD, and FAAH included in the list of DEGs in the analysis of transcriptomes and the list of SNPs associated with BC. Results allow us to suppose that oxylipin signatures reflect the organism’s level of response to the disease. Our data regarding changes in oxylipins at the system level show that oxylipin profiles can be used to evaluate the early stages of breast cancer.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Pleiotropic Impacts on Breast Cancer Occurrence, Development, and Therapy.

Breast cancer (BC) is one of the most devastating cancers, with high morbidity and mortality, among the female population worldwide. In BC, mesenchymal stem cells (MSCs), as pluripotent stromal stem cells, play a significant role in TME formation and tumor progression. Recently, an increasing number of studies have demonstrated that extracellular vesicles (EVs) are essential for the crosstalk between MSCs and BC cells. MSC-derived EVs (MSC-EVs) can deliver a diversity of molecules, including lipids, proteins, and nucleic acids, etc., to target cells, and produce corresponding effects. Studies have demonstrated that MSC-EVs exert both inhibitory and promotive effects in different situations and different stages of BC. Meanwhile, MSC-EVs provide novel therapeutic options for BC, such as EVs as carriers for drug delivery. Therefore, in this review, we summarize the role of MSC-EVs in BC progression and application in clinical treatment, in the hope of providing a basis for further research.

FOXO1 Gene Downregulation and Promoter Methylation Exhibits Significant Correlation With Clinical Parameters in Indian Breast Cancer Patients.

Background: Forkhead box “O” one which is member of Forkhead box family of transcription factors is known to play key role in different physiological processes including cell cycle arrest, autophagy, and apoptosis. FOXO1 is defined to play tumor suppressive role in various malignancies including breast cancer and its Dysregulation is frequently reported. However, the evaluation of FOXO1 promoter methylation and its expression at mRNA and protein level in different stages of breast cancer and its association with different clinical parameters is still not studied. Therefore, for better understanding the role of FOXO1 in breast cancer, in our study we examined the FOXO1 mRNA and protein expression in Breast cancer samples of Indian breast cancer patients. Results: Total 127 breast cancer samples along with adjacent normal tissue (n = 127) were analyzed through methylation specific PCR (MS-PCR), mRNA expression (Real-time PCR) and Immunohistochemistry (IHC). We detected 69.29% cases to be downregulated at the mRNA level, and 77.95% of cases exhibited no or low protein expression. In our data we report a significant association (p = 0.0001) between the downregulated protein expression and promoter hypermethylation of FOXO1 gene. We also found a significant correlation of FOXO1 mRNA level with Age (p = 0.008), age at first live birth (p = 0,003), tumor size (p = 0.05) and lymph node status (p = 0.01). Conclusion: we in our study report the tumor suppressive role of FOXO1 in case of Indian breast cancer patients and our data suggest it to exhibit prognostic importance. However, further research is needed to evaluate FOXO1 significance in diagnostic and therapeutic targeting in breast cancer cases.

Determination of enzyme Q10 level in Pakistani female patients with breast cancer

Coenzyme Q 10 (CoQ 10 ) is a nutrient-like fat substance usually found in the heart, liver, kidney, and pancreas. Breast cancer is the most well-known tumor that has been analyzed and its incidence has been found to increase with age. To determine the levels of CoQ 10 in female patients with breast cancer, 40 blood samples from female patients with different stages of breast cancer (i.e., T-II, T-III, and T-IV) were collected from various breast care clinics in Sindh, Pakistan. These samples were analyzed using high-performance liquid chromatography with diode-array detection. The results showed that CoQ 10 levels in the patients with stage T-II breast cancer in the age range of 29‒61 years were 0.29‒0.36 µg/mL. The patients with stage T-III breast cancer in the age range of 25‒65 years showed CoQ 10 levels of 0.13‒0.19 µg/mL. The patients with stage T-IV breast cancer in the age range of 28‒73 years exhibited CoQ 10 levels of 0.09‒0.16 µg/mL. The CoQ 10 levels in the control samples were in the range of 0.26‒0.73 µg/mL. It was observed that as the stage of cancer progresses, the CoQ 10 level decreases. This remarkable reduction may be a result of the chemotherapy treatment given to the patients, their diet, and socioeconomic status.

Breast Thermography as an Adjunct Tool to Monitor the Chemotherapy Response in a Triple Negative BIRADS V Cancer Patient: A Case Study.

Prior studies have reported that breast thermography is a potential adjunct tool to mammography in early cancer detection, especially in developing countries with limited medical facilities. This non-invasive, safe, and painless screening tool can reduce the mortality due to cancer by early detection and monitoring. This prospective study aims to analyze changes in static breast thermograms of a BIRADS V category breast cancer patient to assess the response to Neoadjuvant chemotherapy (NACT) in locally advanced cancer and to compare with thermograms of a BIRADS II category benign patient. Breast thermograms of the malignant and benign patients in five different views were taken using FLIR E40 thermal camera under strict acquisition protocols. Details of the patient along with the thermograms were recorded pre and post NACT. There is a qualitative reduction in the warm region of the surface after the first cycle of chemotherapy treatment. Thermal, fractal, and statistical analysis of thermograms is performed for both patients. In the patient with aggressive ductal carcinoma, the difference in the mean surface temperature between contralateral breasts is high, which is reduced after the first cycle of NACT. This preliminary study indicates that breast thermography can potentially be used as an effective non-invasive, non-contact, and radiation-free tool to analyze the effect of NACT on patients with different stages of breast cancer. This study also signifies the role of the thermography technique in reaching a largely rural population with limited medical resources for early cancer screening.

Abstract P3-12-37: The impact of the COVID-19 outbreak on breast cancer stage in the Netherlands by screening status

Abstract Introduction: The COVID-19 outbreak led to the suspension of the Dutch breast cancer screening program, increased the reluctance of patients to visit the general practitioner (GP), and led to a lack of capacity at the GP. As a consequence, the incidence of breast cancer diagnoses decreased. Objective: This study aimed to investigate the impact of the COVID-19 outbreak on the incidence of different stages of breast cancer, by screening status. Methods: Women diagnosed between January 1st 2017 and February 28th 2021 with primary breast cancer without a history of breast cancer were selected from the Netherlands Cancer Registry. March 1st 2020 till February 28th 2021 was regarded as the COVID-19 period. Breast cancer incidence within this COVID-19 period was calculated by tumor stage and compared with the incidence in 2017/2019 (reference). Incidence was expressed per 100,000 women aged 18 year or older, living in the Netherlands at the start of the year. Thereafter, the COVID-19 period was divided into four subperiods, based on COVID-19 related events: March-April 2020, May-June 2020, July-August 2020, September 2020-February 2021. Incidence in each of those periods was calculated by tumor stage and compared with the incidence in 2017/2019. Analyses were further stratified by screening status. Incidence of screen-detected tumors was expressed per 100,000 women aged 50-74 living in the Netherlands at the start of the year. Results: A total of 15,916 women were diagnosed in 2017, 15,574 in 2018, 15,867 in 2019, 13,497 in 2020 and 2,532 up to February 2021. Compared to 2017/2019, the incidence of DCIS and stage I-III tumors was statistically significantly lower during the COVID-19 period (32%, 24%, 9% and 11% respectively) (Table 1), leading to 603, 1539, 520 and 160 missed diagnoses respectively. The incidence of stage IV tumors was 5% higher, however this was not significant. The incidence of DCIS remained significantly lower throughout the four subperiods, while the incidence of stage I-II tumors was comparable with 2017/2019 in September 2020-February 2021 and the incidence of stage III was comparable with 2017/2019 in both July-August 2020 and September 2020-February 2021. The incidence of DCIS and stage I-II non-screen-detected tumors was significantly lower during March-April 2020 and was comparable with 2017/2019 in the subperiods thereafter. The incidence of DCIS and stage I-IV screen-detected tumors was significantly lower during March 2020-February 2021, with the incidence of DCIS and stage I-III tumors being lower during each subperiod and the incidence of stage IV tumors being lower during May-June 2020. Conclusion: The COVID-19 outbreak led to a decrease in the incidence of DCIS and stage I-III tumor diagnoses, which still lags behind in February 2021. Until February 2021 no stage shift was seen. Incidence of breast cancer diagnoses per tumor stage and screening statusDCISStage IStage IIStage IIIStage IVReference126.590.876.820.411.0COVID-19 period218.069.269.518.111.5March - April reference14.515.112.73.61.8March - April 20202.28.18.48.41.4May - June reference14.115.413.83.71.9May - June 20201.57.510.52.91.9July - August reference14.315.413.13.31.9July - August 20202.310.711.63.42.2September - February reference113.644.937.39.85.4September 2020 - February 202112.042.939.09.26.0Non-screen-detectedDCISStage IStage IIStage IIIStage IVReference18.841.258.817.910.4COVID-19 period27.639.958.016.611.2March - April reference11.46.99.73.11.7March - April 20200.95.07.02.61.4May - June reference11.67.610.83.11.9May - June 20201.47.210.52.91.9July - August reference11.36.910.03.01.8July - August 20201.16.910.23.22.1September - February reference14.519.828.28.55.1September 2020 - February 20214.320.830.38.05.8Screen-detected3DCISStage IStage IIStage IIIStage IVReference145.3127.146.36.31.3COVID-19 period226.374.127.02.90.6March - April reference18.021.07.51.20.2March - April 20203.58.03.30.20.1May - June reference16.520.17.51.10.2May - June 20200.30.70.20.10.0July - August reference17.621.78.00.80.3July - August 20203.29.73.60.40.1September - February reference123.364.323.33.30.7September 2020 - February 202119.355.819.92.20.4Incidence is expressed per 100,000 women living in the Netherlads Bold: the incidence in that period of 2020/2021 is statistically significantly lower/higher compared to the incidence in the same period of 2017/2019 (averaged) 1. Reference period: 2017/2019 2. COVID-19 period: March 2020 -February 2021 3. Expressed per 100,000 women aged 50-74 years Citation Format: Anouk H Eijkelboom, Sabine Siesling, Linda de Munck, Carla H van Gils, Marc BI Lobbes, Vivianne CG Tjan-Heijnen, Luc JA Strobbe, Jelle Wesseling, Ruud M Pijnappel, Mireille JM Broeders, NABON-COVID-19 consortium, COVID and Cancer Care-NL consortium (ZONMW number10430022010014). The impact of the COVID-19 outbreak on breast cancer stage in the Netherlands by screening status [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-37.

Abstract P4-04-08: Determination of PD-L1 expression on tumorspheres cultured from the peripheral blood in patients with breast cancer

Abstract Background Cancer stem cells (CSCs) are the critical subpopulation of cancer cells involved in tumor formation, progression, metastasis and drug resistance. CSCs also have been considered as the main cause of cancer recurrence. The exact role of CSCs in escape of cancer from immunosurveillance is still unknown, but recent studies revealed that enhanced PDL-1 expression in cancer stem cells is linked to 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 the peripheral blood in patients with breast cancer.Methods:110 patients with breast cancer in different stages of disease were included in this study. The determination of circulating tumor cells and circulating cancer stem cells (cCSC) was performed using maintrac and tumorsphere forming assay, respectively. Additionally anti-PDL-1 antibody staining was applied to examine PDL-1 expression on breast tumorspheres.Results:We developed an innovative in vitro platform for cultivation of CSCs from peripheral blood of solid cancer patients and confirmed for the first time that tumorspheres are positive for PDL-1 in breast cancer patients. Our data also show a considerable heterogeneity in the PDL-1 expression of tumorspheres. We confirmed once again that the number of tumorspheres increased significantly with tumor progression, especially with presence of metastasis. 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 proliferating index Ki-67 and grade score in primary breast tumor. Moreover, patients with HER2 positive tumors had more tumorspheres compared to patients with HER2 negative primary tumors (35 vs 10/100 µl blood, p&amp;lt;0.005). 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 immunregulatory potential, but further studies are needed to validate the impact of PDL-1 expression on tumorspheres in patients with breast cancer. Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. Determination of PD-L1 expression on tumorspheres cultured from the peripheral blood in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-04-08.