Types Of Breast Cancer Research Articles

Abstract 2987: microRNA (miRNA) a putative biomarker to better define the molecular apocrine breast cancer (MABC) subtype

Abstract Background: Breast cancer (BC), is a highly heterogeneous disease, divided into molecular subtypes based on gene expression and clinical outcomes. Transcriptomics profiling depicted a subtype that has luminal expression profile but lacks estrogen receptor (ER), progesterone receptor expression with an overlapping expression of HER-2; yet it overexpresses androgen receptor (AR). This subtype was referred to as MABC and constitutes 8-14% of all BC types. At present MABC is often misdiagnosed with triple negative BC (TNBC). Its improper diagnosis demands the adoption of complementary tools; miRNA, key players in BC tumorigenic processes, hold promise in defining MABC. Methods: 539 BC microarray data were downloaded from The Cancer Genome Atlas (TCGA-BRCA) (PMID: 25691825) using TCGA biolinks R/Bioconductor package (PMID:267704973). Cases with available miRNA data were retained and classified using citbcmst R package (PMID: 21785460). Differential expression analysis identified deregulated miRNAs using DEseq2. The validation set consists of 111 ER-neg samples (68 MABC, and 43 TN samples) with an average age at diagnosis 58.51 years and a median follow-up=78.5 months. MABC tumors were characterized apart of TNBC by the molecular signature (AR, FOXA1 and AR-related genes, PMID: 25516281) on fresh tissue sections. Using miRCURY LNATM miRNA PCR assay, miRNA profiling was done for a panel of differentially expressed miRNAs. Non tumorigenic (MCF-10A) and BC Cellular models MABC (MDA-MB-453) and TNBC (MDA-MB-231) were used to investigate the invasive potential of MABC. Results: TCGA data analysis indicated MABC as a separate entity based on gene signature. MiRNA-seq data analysis depicted a set of 6 significantly deregulated miRNA with absolute value of log2 fold change> 1 and P-adjusted value <0.05 between MABC and TNBC. We validated, by miRNA profiling, significant upregulation of miR-2115-3p and miR-187-3p in MABC compared to TNBC. These miRNAs significantly differentiate MABC patients from TNBC patients where the combined miRNA panel of miR-2115-3p and miR-187-3p had an area under the curve of 0.904 ±0.28 (P<0.0001 and 95% CI: 0.850-0.958) and sensitivity, specificity, and a diagnostic accuracy of 90.41%, 81.1%, and 86.5% respectively. Preliminary data, showed that non-tumorigenic/non-invasive MCF-10A had a significant increase in its invasive ability upon transfection with miR-187-3p mimic (P<0.05). Similarly, the invasive cell line MDA-MB-231 showed a significant increase in invasion upon transfection with miR-187-3p mimic (P<0.05). On the other hand, only miR-187-3p inhibitor significantly decreased the invasive potential of MDA-MB-453 cells (P<0.05). Conclusion: MABC has a unique signature of miRNA as compared to TNBC. miR-2115-3p, and miR-187-3p could be potential diagnostic biomarkers for MABC. The invasive potential of MABC could be attributed to miR-187-3p activity. Citation Format: Ghada Chamandi, Adrien Borgel, Abdallah Kurdi, Pierre Khoueiry, Luis Teixeira, Morgane Le Bras, Jacqueline Lehamnn, Rihab Nasr. microRNA (miRNA) a putative biomarker to better define the molecular apocrine breast cancer (MABC) subtype [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 2987.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

Deubiquitinase BRCC3 promotes the migration, invasion and EMT progression of colon adenocarcinoma by stabilizing MET expression.

Breast cancer type 1 susceptibility protein/breast cancer type 2 susceptibility protein-containing complex subunit 3 (BRCC3), a deubiquitinase (DUBs), is overexpressed in various cancers. However, the underlying biological roles of BRCC3 in adenocarcinoma colon (COAD) have yet to be decrypted. In this work, we explored the potential biological function of BRCC3 in the natural process of COAD cells. The expression levels of BRCC3 in COAD tissues and cell lines were investigated via quantitative real time polymerase chain reaction and western blotting analyses. Meanwhile, short hairpin RNAs targeting BRCC3 (sh-BRCC3) or mesenchymal-epithelial transition factor (MET) (sh-MET) were used to investigate the biological function, including proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) progression in COAD cells. Furthermore, the expression levels of EMT-related biomarkers were detected with western blotting analysis. Furthermore, we also performed Co-IP assay to identify the correlation between BRCC3 and MET. BRCC3 expression was increased in COAD tissues and cell lines. ShRNA-mediated downmodulation of BRCC3 in COAD cell lines induced EMT progression. BRCC3 knockdown resulted in decreased migration as well as invasion and increased apoptosis of SW480 and Lovo cells. Besides, MET was regulated by BRCC3 and involved in the migration, invasion, and EMT in SW480 and Lovo cells. Finally, we uncovered that the overexpressed MET reversed the effects of BRCC3 knockdown in COAD cell development. BRCC3 acted as a critical factor in the development of COAD by deubiquitinating and stabilizing MET, which might provide an emerging biomarker for the therapeutic and diagnosis strategy of COAD.

Incidence and risk factors of breast cancer-related lymphedema in Korea: A nationwide retrospective cohort study.

Breast cancer-related lymphedema (BCRL) is a secondary lymphedema that occurs after breast cancer related treatments. BCRL develops from damage or dysfunction of the normally functioning lymphatic system due to surgery, radiation therapy and rarely due to cancer recurrence. This nationwide, retrospective study was aimed at investigating the incidence and risk factors of BCRL using the database of the Korean National Health Insurance Service (NHIS). Patients with newly diagnosed breast cancer who underwent breast surgery from January 1, 2017 to December 31, 2020, were recruited. The incidence was compared by four groups according to the operation type of breast cancer (breast conserving surgery (BCS) with sentinel lymph node biopsy (S), BCS with axillary lymph node dissection (A), total mastectomy (TM) with S, modified radical mastectomy(MRM)). The incidence rates of lymphedema were calculated by the number of incident events by the total follow-up period. Cox proportional hazard regression was used to calculate the risk of incidence of lymphedema based on a patients' characteristics, breast cancer treatment and comorbidities. The final cohort of operation subjects that satisfied the inclusion criteria was 34,676. BCRL occurred in 4,242 patients (12.2%), and the median follow-up period was 695.4 days. The BCRL was diagnosed in the BCS with S (8.0%), BCS with A (23.5%), TM with S (10.7%), MRM (28.5%) with an incidence of 40.8, 132.2, 55.8 and 171.8 per 1,000 person-years, respectively. Young age, obesity, chemotherapy, radiotherapy, residence in metropolitan areas and hyperlipidemia were identified as risk factors. In Korea, the incidence of BCRL was found to be 12.2%, with the highest risk observed among patients who underwent MRM. Therefore, surgical oncologists should meticulously assess the appropriate surgical approach and consider providing education to patients with risk factors for BCRL, aiming to ensure effective prevention strategies.

Vulnerability of Store-Operated Calcium Entry to Inhibitors and Microenvironment in Cells of Different Breast Cancer Subtypes.

The incidence and development of cancer are highly dependent on pathological disturbances in calcium homeostasis of the cell. One of the major pathways for calcium entry is store-operated calcium entry (SOCE), which functions in virtually all cell types. Changes in the expression level of the main proteins organizing SOCE are observed during the development of various cancer types, particularly breast cancer (BC). This leads to unique SOCE with characteristics individual for each type of BC and requires particular therapeutic approaches. In this study, we tested the sensitivity of SOCE in various BC cells to selective ORAI channel inhibitors and the less selective compounds Leflunomide and Teriflunomide, approved by the FDA for clinical use. We also analyzed the vulnerability of SOCE to the influence of factors typical of the tumor microenvironment: hypoxia and acidification. We have observed that the SOCE inhibitors Leflunomide and Teriflunomide suppress SOCE in the triple-negative BC cell line MDA-MB-231, but not in the luminal A BC cell line MCF-7. MDA-MB-231 cells also demonstrate higher pH dependence of SOCE compared to MCF-7 cells. In addition, the oxygen scavenger sodium dithionide also affects SOCE, stimulating it in MDA-MB-231 cells but inhibiting in MCF-7 cells. Overall, our data highlight the importance of considering the different sensitivities of various BC cell types to inhibitors and to microenvironmental factors such as hypoxia and acidification when developing targeted drugs.

Design, optimization, characterization, and in vitro evaluation of metformin-loaded liposomes for triple negative breast cancer treatment

Recently, metformin (Met) has shown to have antineoplastic properties in cancer treatment by improving hypoxic tumor conditions, and causing reduction in the synthesis of biomolecules, which are vital for cancer growth. However, as an orally administered drug, Met has low bioavailability and rapid renal clearance. Thus, the goal of this study was to vectorize Met inside liposomes in the context of triple negative breast cancer (TNBC), which currently lacks treatment options when compared to other types of breast cancer. Vectorization of Met inside liposomes was done using Bangham method by implementing double design of experiment methodology to increase Met drug loading (minimum-run resolution V characterization design and Box-Behnken design), as it is generally extremely low for hydrophilic molecules. Optimization of Met-loaded liposome synthesis was successfully achieved with drug loading of 190 mg/g (19% w/w). The optimal Met-liposomes were 170 nm in diameter with low PdI (< 0.1) and negative surface charge (-20 mV), exhibiting sustained Met release at pH 7.4. The liposomal Met delivery system was stable over several months, and successfully reduced TNBC cell proliferation due to the encapsulated drug. This study is one the first reports addressing liposome formulation through thin-film hydration using two design of experiment methods aiming to increase drug loading of Met.

Analyses of hypoxia-related risk factors and clinical relevance in breast cancer.

Hypoxia plays an important role in the heterogeneity, relapse, metastasis, and drug resistance of breast cancer. In this study, we explored the hypoxia-related biological signatures in different subtypes of breast cancer and identified the key prognostic factors by bioinformatics methods. Based on The Cancer Genome Atlas (TCGA) Breast Cancer datasets, we divided the samples into immune-activated/suppressed populations by single-sample gene set enrichment analysis (ssGSEA) and then used hierarchical clustering to further identify hypoxic/non-hypoxic populations from the immune-suppressed samples. A hypoxia related risk model of breast cancer was constructed. Nuclear factor interleukin-3 regulated (NFIL3), serpin family E member 1 (SERPINE1), FOS, biglycan (BGN), epidermal growth factor receptor (EGFR), and sushi-repeat-containing protein, X-linked (SRPX) were identified as key hypoxia-related genes. Margin status, American Joint Committee on Cancer (AJCC) stage, hypoxia status, estrogen receptor/progesterone receptor (ER/PR) status, NFIL3, SERPINE1, EGFR, and risk score were identified as independent prognostic indicators for breast cancer patients. The 3- and 5-year survival curves of the model and immunohistochemical staining on the breast cancer microarray verified the statistical significance and feasibility of our model. Among the different molecular types of breast cancer, ER/PR+ and HER2+ patients might have higher hypoxia-related risk scores. ER/PR-negative samples demonstrated more activated immune-related pathways and better response to most anticancer agents. Our study revealed a novel risk model and potential feasible prognostic factors for breast cancer and might provide new perspectives for individual breast cancer treatment.

Imaging Characteristics and Hormonal Receptor Correlations in Varieties of Breast Cancer

Background: While there is acknowledgment of the vital role of factors such as the status of histological grades and hormone receptor (HR) in shaping targeted treatment strategies for breast cancer (BC), comprehensive research that unifies the study of imaging features with the evaluation of HR characteristics and histopathological data is notably absent in Albania, creating a critical research gap that this study endeavors to fill. This study aimed to investigate the imaging characteristics observed in ultrasound and the possible correlations between expression levels of HRs in ductal and lobular types of BC to elucidate potential prognostic and therapeutic implications. Methods and Results: This descriptive study, conceived as a series of cases, leveraged a prospective approach to scrutinize the dynamics of the study population over four years (2019-2023) in the Mother Teresa University Hospital Center and a private oncology clinic in Tirana. The convenience sampling strategy enlisted 238 female patients (mean age 60.5±12.5 years) diagnosed with BC who had been tested for HRs and consented to participate. Diagnostic imaging was facilitated using a Chison US equipped with a 10 MH linear probe. The results were adjudged based on the BI-RADS tumor classification.HR markers were discerned through rigorous immunohistochemical analyses. Utilizing SPSS version 21.0, statistical analyses incorporated a variety of tests, including Spearman's rho to assess correlations between hormonal receptors and imaging morphological characteristics and ordinal logistic regression to evaluate the relationships between hormonal receptors and cancer grades. Analyzing the localization of the tumor revealed that a slightly higher proportion had it on the left side, accounting for 52.9% compared to 47.1% on the right side. Regarding the BI-RADS classification observed through echographic examination, a vast majority were classified as BI-RADS 5 (92.8%), followed by a smaller percentage distributed amongst BI-RADS 4 (5.9%), BI-RADS 3 (0.84%), and BIRADS 6 (0.42%). Examining the cancer grades determined that 68.3% were at Grade 2, whereas Grades 1 and 3 were noticeably less common, standing at 1.7% and 30.2%, respectively. Estrogen receptor (ER) and progesterone receptor (PgR) sensitivity were high in most patients, exhibiting 77.7% and 70.6% positivity, respectively, alongside a notable presence of high Ki67 levels in 75.2% of the individuals. The investigation into HER2 status demonstrated that a significant number were negative (76.1%), as opposed to 17.6% being positive and 6.3% equivocal. Remarkably, 5.5% of the patients had a triple-negative status upon biopsy evaluation.The Spearman's rho correlations displayed a moderate positive correlation between ER and PgR (rho=0.563) and a weak negative correlation between ER and Ki67 (rho=-0.343) (P&lt;0.05 in both cases). PgR and Ki67 show a weak negative correlation (rho=-0.353, P&lt;0.05), suggesting a tendency for higher PgR values to correspond with lower Ki67 values. The ordinal logistic regression analysis identified a statistically significant negative relationship between the ER variable and the outcome variable, denoted by a coefficient of -2.137, P&lt;0.05. Additionally, Ki67 showcased a positive relationship with the outcome, as indicated by a coefficient of 5.150, P&lt;0.05. Conclusion: This study delineates the nuanced relationships between biomarkers such as ER, PgR, and Ki67 in different types of infiltrative cancers, pointing to a complex interplay that necessitates further exploration while also noting the independence of BI-RADS imagery in these correlations.

Classification of Early Breast Cancer using Convolutional Neural Networks

Breast cancer is a life-threatening disease that impacts millions of people worldwide, necessitating heightened awareness and effective early detection strategies. Current methods for determining the presence and type of breast cancer in a clinical breast exam conducted by healthcare providers may be inaccurate, imprecise, and prone to error. The goal of this research project is to offer a second opinion for physicians to predict whether or not a patient has early onset breast cancer through a machine learning model developed from an image dataset, to significantly reduce the error in breast cancer staging, making the process more efficient in healthcare. Early detection is crucial for successful treatments of breast cancer, as treatment options in late-stage diagnosis of breast cancer can have a much worse prognosis. In the US, 240,000 cases of breast cancer are diagnosed per year in both men and women with a mortality rate of approximately 42,000 per year. [1] To approach this problem, I have tested an MLP Classifier, Logistic Regression, Ridge Classifier, Random Forest Classifier, Decision Tree Classifier, Support Vector Classifier, and trained a Convolutional Neural Network to compare various results and determine the best accuracy. The Convolutional Neural Network yielded impressive outcomes, reaching up to 79% testing accuracy and 98% training accuracy. The final model exhibits the capability to identify early signs of breast cancer and differentiate between malignant and benign tumours with relatively high accuracy showing the potential of AI in combination with medical imaging that can assist medical staff in diagnosis.

A comprehensive evaluation of the therapeutic potential of silibinin: a ray of hope in cancer treatment.

Natural compounds hold promise in the search for cancer therapies due to their unique chemical structures and combinations that may effectively combat cancer while minimizing toxicity and side effects compared to conventional treatments. Silibinin, a natural lignan, has been found to possess strong anti-cancer activity against several types of human cancers based on emerging research. This study aims to provide an overview of the therapeutic potential of silibinin in the treatment and prevention of cancers. A comprehensive search was conducted using various internet databases such as PubMed, Google Scholar, and ScienceDirect to identify relevant research papers. Silibinin has been shown to exhibit anticancer activity against several types of cancers, including liver, lungs, breast, prostate, colorectal, skin, and bladder cancers. Its multifaceted mechanisms of action contribute to its therapeutic effects. Silibinin exerts antioxidant, anti-inflammatory, anti-proliferative, pro-apoptotic, anti-metastatic, and anti-angiogenic activities, making it a promising candidate for cancer therapy. One of the key mechanisms underlying the anticancer effects of silibinin is its ability to modulate multiple signaling pathways involved in cancer development and progression. It can inhibit the activation of various oncogenic pathways, including PI3K/Akt, NF-κB, Wnt/β-catenin, and MAPK pathways, thereby suppressing cancer cell proliferation, inducing cell cycle arrest, and promoting apoptosis. Silibinin possesses great potential as an effective treatment agent for cancer. The multifaceted mechanisms of action, favorable safety profile, and potential synergistic effects of silibinin with conventional therapies make it an attractive candidate for further investigation and development as a cancer treatment. However, more extensive clinical studies are necessary to fully establish the efficacy, optimal dosage, and long-term effects of silibinin in cancer treatment.

Clear View Cancer-AI

Abstract: Brest tumor is one of the most dangerous diseases in females. There are a variety of breast cancer; the type of breast cancer depends on which cells turn into cancer. It is so crucial to identify the disease in the early stage so that it can be treated comfortably. Machine learning Machine learning stands out as an exceptionally potent tool to detect cancer in breast. Machine learning facilitates the training of machine and creating some models which can predict the chances of breast cancer . Among the prevalent techniques in machine learning classifier for breast cancer identification are SVM, Naive Bayes, Logistic regression, KNN, Random Forest, AdaBoost, Random Forest, Decision tree, and XGBoost. The motive of this research is to find out the best machine-learning technique which provides the most accuracy for the detection of breast cancer. The precision of machine learning models can differ for dissimilar datasets. This research has been tested across various datasets of large and small sizes and after analyzing the accuracies of these machine learning techniques the conclusion is drawn.

Isocitrate dehydrogenase 2 regulates the proliferation of triple-negative breast cancer through the ferroptosis pathway.

Triple-negative breast cancer (TNBC) is currently the type of breast cancer with the worst prognosis; it lacks specific treatments, such as ER/PR antagonistic endocrine and anti-HER2 targeted therapies. Although immunotherapy with immune checkpoints has shown some efficacy in many solid tumors, clinical data in TNBC suggest significant limitations. The essence of ferroptosis is the impaired metabolism of intracellular lipid oxides, which in turn causes the activation and abnormalities of the immune system, including ROS, and not only plays an important role in liver injury and organ aging but also a large amount of data points to the close correlation between the ferroptosis process and tumor development. In this study, through the analysis of large-throughput biological data of breast tumors, combined with the characteristics of the biological process of ferroptosis, the specific gene IDH2 was found to be significantly highly expressed in TNBC and functionally correlated with ferroptosis. Through clinical specimens validated at the gene and protein levels, in vitro tumor cell line validation, and in vivo mouse models, we found that the high expression of IDH2 in TNBC has a role in inhibiting the ferroptosis process in TNBC, thus promoting the proliferation of TNBC cells and other malignant features.

N- and s-substituted Pyrazolopyrimidines: A promising new class of potent c-Src kinase inhibitors with prominent antitumor activity

In this work, readily achievable synthetic pathways were utilized for construction of a library of N/S analogues based on the pyrazolopyrimidine scaffold with terminal alkyl or aryl fragments. Subsequently, we evaluated the anticancer effects of these novel analogs against the proliferation of various cancer cell lines, including breast, colon, and liver lines. The results were striking, most of the tested molecules exhibited strong and selective cytotoxic activity against the MDA-MB-231 cancer cell line; IC50 1.13 µM. Structure-activity relationship (SAR) analysis revealed that N-substituted derivatives generally enhanced the cytotoxic effect, particularly with aliphatic side chains that facilitated favorable target interactions. We also investigated apoptosis, DNA fragmentation, invasion assay, and anti-migration effects, and discussed their underlying molecular mechanisms for the most active compound 7c. We demonstrated that 7c N-propyl analogue could inhibit MDA-MB-231 TNBC cell proliferation by inducing apoptosis through the regulation of vital proteins, namely c-Src, p53, and Bax. In addition, our results also revealed the potential of these compounds against tumor metastasis by downregulating the invasion and migration modes. Moreover, the in vitro inhibitory effect of active analogs against c-Src kinase was studied and proved that might be the main cause of their antiproliferative effect. Overall, these compelling results point towards the therapeutic potential of these derivatives, particularly those with N-substitution as promising candidates for the treatment of TNBC type of breast cancer.

Neutrophil extracellular trap-associated risk index for predicting outcomes and response to Wnt signaling inhibitors in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a type of breast cancer with poor prognosis, which is prone to distant metastasis and therapy resistance. The presence of neutrophil extracellular traps (NETs) contributes to the progression of breast cancer and is an efficient predictor of TNBC. We obtained the bulk and single-cell RNA sequencing data from public databases. Firstly, we identified five NET-related genes and constructed NET-related subgroups. Then, we constructed a risk index with three pivotal genes based on the differentially expressed genes between subgroups. Patients in the high-risk group had worse prognosis, clinicopathological features, and therapy response than low-risk group. Functional enrichment analysis revealed that the low-risk group was enriched in Wnt signaling pathway, and surprisingly, the drug sensitivity prediction showed that Wnt signaling pathway inhibitors had higher drug sensitivity in the low-risk group. Finally, verification experiments in vitro based on MDA-MB-231 and BT-549 cells showed that tumor cells with low-risk scores had less migration, invasion, and proliferative abilities and high drug sensitivity to Wnt signaling pathway inhibitors. In this study, multi-omics analysis revealed that genes associated with NETs may influence the occurrence, progression, and treatment of TNBC. Moreover, the bioinformatics analysis and cell experiments demonstrated that the risk index could predict the population of TNBC likely to benefit from treatment with Wnt signaling pathway inhibitors.

Breast Conserving Surgery (BCS) is Superior to Mastectomy in Early Stage Triple Negative Breast Cancer (TNBC) a Comparative Study

Background: Breast cancer is the most prevalent form of cancer in women worldwide and the second-leading cause of death from cancer in women. Because the estrogen receptor, progesterone receptor, and HER2 are not expressed, triple-negative breast cancer (TNBC) has an aggressive clinical history. The highest rates of recurrence and survival, higher average grades, and larger tumor sizes at diagnosis are all characteristics of TNBC. Objective: To compare between breast conserving surgery (BCS) and mastectomy patients with early stage Triple negative breast cancer (TNBC). Materials and Methods: We conducted a comparative retrospective monocentric study that evaluated TNBC patients treated with upfront surgery at CMH Dhaka, CMH Bogura and Kurmitola General Hospital, Dhaka. The observation period was from 1 January 2021 to 31 December 2022. All patients received biopsy to obtain the pathological tissue before treatment, and their immunohistochemical results met the diagnostic criteria for TNBC. Study patients divide din to two group 40 surgeries with primary site were categorized as receiving BCS and other hand 40 surgeries with categorized as receiving mastectomy. BCSS and OS were the primary outcomes of our study. Results: Tumor grade II, tumor size &gt;20.0 mm and lymph node 2 were significantly associated with breast cancer-specific survival. Tumor size &gt;20.0 mm and lymph node 2 were significantly associated with TNBC survival. Conclusion: TNBC is a breast cancer type that is aggressive and has a bad prognosis. With regard to breast cancer-specific survival, advanced age, being single, left side of laterality, tumor grades II and III, large tumor size, and lymph node 2 were all substantially related.

MTFN: multi-temporal feature fusing network with co-attention for DCE-MRI synthesis.

Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) plays an important role in the diagnosis and treatment of breast cancer. However, obtaining complete eight temporal images of DCE-MRI requires a long scanning time, which causes patients' discomfort in the scanning process. Therefore, to reduce the time, the multi temporal feature fusing neural network with Co-attention (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables the acquisition of DCE-MRI images without scanning. In order to reduce the time, multi-temporal feature fusion cooperative attention mechanism neural network (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables DCE-MRI image acquisition without scanning. In this paper, we propose multi temporal feature fusing neural network with Co-attention (MTFN) for DCE-MRI Synthesis, in which the Co-attention module can fully fuse the features of the first and third temporal image to obtain the hybrid features. The Co-attention explore long-range dependencies, not just relationships between pixels. Therefore, the hybrid features are more helpful to generate the eighth temporal images. We conduct experiments on the private breast DCE-MRI dataset from hospitals and the multi modal Brain Tumor Segmentation Challenge2018 dataset (BraTs2018). Compared with existing methods, the experimental results of our method show the improvement and our method can generate more realistic images. In the meanwhile, we also use synthetic images to classify the molecular typing of breast cancer that the accuracy on the original eighth time-series images and the generated images are 89.53% and 92.46%, which have been improved by about 3%, and the classification results verify the practicability of the synthetic images. The results of subjective evaluation and objective image quality evaluation indicators show the effectiveness of our method, which can obtain comprehensive and useful information. The improvement of classification accuracy proves that the images generated by our method are practical.

An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer

Individual cancers are composed of heterogeneous tumor cells with distinct phenotypes and genotypes, with triple negative breast cancers (TNBC) demonstrating the most heterogeneity among breast cancer types. Variability in transcriptional phenotypes could meaningfully limit the efficacy of monotherapies and fuel drug resistance, although to an unknown extent. To determine if transcriptional differences between tumor cells lead to differential drug responses we performed single cell RNA-seq on cell line and PDX models of breast cancer revealing cell subpopulations in states associated with resistance to standard-of-care therapies. We found that TNBC models contained a subpopulation in an inflamed cellular state, often also present in human breast cancer samples. Inflamed cells display evidence of heightened cGAS/STING signaling which we demonstrate is sufficient to cause tumor cell resistance to chemotherapy. Accordingly, inflamed cells were enriched in human tumors taken after neoadjuvant chemotherapy and associated with early recurrence, highlighting the potential for diverse tumor cell states to promote drug resistance.

Cyclin-dependent kinase 7 (CDK7) inhibitors as a novel therapeutic strategy for different molecular types of breast cancer.

Cyclin-dependent kinase (CDK) 7 is aberrantly overexpressed in many types of cancer and is an attractive target for cancer therapy due to its dual role in transcription and cell cycle progression. Moreover, CDK7 can directly modulate the activities of estrogen receptor (ER), which is a major driver in breast cancer. Breast cancer cells have exhibited high sensitivity to CDK7 inhibition in pre-clinical studies. In this review, we provide a comprehensive summary of the latest insights into CDK7 biology and recent advancements in CDK7 inhibitor development for breast cancer treatment. We also discuss the current application of CDK7 inhibitors in different molecular types of breast cancer to provide potential strategies for the treatment of breast cancer. Significant progress has been made in the development of selective CDK7 inhibitors, which show efficacy in both triple-negative breast cancer (TNBC) and hormone receptor-positive breast cancer (HR+). Moreover, combined with other agents, CDK7 inhibitors may provide synergistic effects for endocrine therapy and chemotherapy. Thus, high-quality studies for developing potent CDK7 inhibitors and investigating their applications in breast cancer therapy are rapidly emerging. CDK7 inhibitors have emerged as a promising therapeutic strategy and have demonstrated significant anti-cancer activity in different subtypes of breast cancer, especially those that have been resistant to current therapies.

CDH1 gene as biomarker towards breast cancer prediction*

Breast cancer is considered to be happened due to genetic aberration. Out of several genes expressed, it is found that cadherin 1, type 1 (CDH1) is responsible in several ways to control the metabolic order in human. Deregulation of the function of protein E-cadherin, expressed from CDH1 plays an important role in lobular breast cancer. In order to understand the root cause of this recent claim, we focus on CDH1 gene: whether the genetic information translated due to any deviation/alteration/modification in its sequence is related to the occurrence of the different types breast cancer. Towards this end, quantitative analysis of different biophysical and bio-chemical properties of CDH1 gene in genomic and proteomic levels from the available genomic (cDNA) sequences of CDH1 gene (obtained from the COSMIC Database for 78 patients, suffering from various types of breast cancer) clearly emphasizes that alternation/modification in the sequence of the CDH1 gene can be detrimental. Furthermore, Random forest, K-nearest neighbour and stochastic gradient descent (SGD) algorithms are applied on the derived dataset to classify the types of breast cancer, and to validate our hypothesis regarding the acute role of CDH1 as potential bio marker for breast cancer. Analysis of the mutated CDH1 gene sequences, and their related parameters using aforesaid machine learning techniques clearly establish that CDH1 gene can take the deterministic role in predicting the chances of occurrences of different types of breast cancer with an accuracy of > 90 % . Such an observation opens a new paradigm in diagnostic approach of breast cancer. Communicated by Ramaswamy H. Sarma

Management of Neuroendocrine Breast Carcinoma (NEBC): Review of Literature.

Extra pulmonary high-grade poorly differentiated neuroendocrine carcinomas (EP-NECs) are rare tumors that usually arise in the gastrointestinal and genitourinary tracts. Primary neuroendocrine carcinoma of the breast (NEBC) is extremely rare, representing less than 0.1% of all breast cancers and less than 1% of neuroendocrine neoplasms. Consequently, they can be misdiagnosed as other types of breast cancer, however, proper immunohistochemical (IHC) studies can assist with making the correct diagnosis. Management of NEBC can be challenging given the paucity of evidence-based literature and should not routinely follow the therapeutic guidelines of other breast cancers. In this article, we review the current literature regarding the management of NEBC.