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BACKGROUND: Breast lump is one of the common surgical problems encountered in female patients. The goal of pathological diagnosis is to distinguish between aggressive carcinomas requiring aggressive treatment and benign lesions that allow for a more conservative approach. METHOD: A cross-sectional study was conducted in which the cytological diagnosis of palpable lesion of the breast was compared with histopathological diagnosis to find sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of FNAC in breast lumps. A total number of 62 fine needle aspiration cytology were performed. Every patient subjected to FNAC underwent a definitive surgical procedure and was subjected to histopathology. RESULTS: Statistical analysis was performed on the tabulated data and sensitivity and specificity with PPV and NPV were obtained. Of all 62 patients selected, only 2 were false negative for malignancy i.e., they were detected as benign lesions on FNAC but found to be malignant on histopathology. Hence, the sensitivity of the study was 92.3% and the specificity for malignant lesions was 100%. The PPV was 100% and the NPV was 94.7% CONCLUSION: Histological correlation indicated FNAC to be a good diagnostic tool as the p-value turned out to be 0.001, considered extremely significant. It gives a good histological correlation. [ABSTRACT FROM AUTHOR]

Cancer diseases constitute a major health problem which leads to the death of millions of people annually. They are unique among other diseases because cancer cells can perfectly adapt to the environment that they create themselves. This environment is usually highly hostile and for normal cells it would be hugely difficult to survive, however neoplastic cells not only can survive but also manage to proliferate. One of the reasons is that they can alter immunological pathways which allow them to be flexible and change their phenotype to the one needed in specific conditions. The aim of this paper is to describe some of these immunological pathways that play significant roles in gynecologic neoplasms as well as review recent research in this field. It is of high importance to possess extensive knowledge about these processes, as greater understanding leads to creating more specialized therapies which may prove highly effective in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: This position paper aims to address specific clinical questions regarding the use of cyclin-dependent kinase 4/6 inhibitors in elderly patients with early or advanced breast cancer. Its objectives are to delineate the current state of knowledge regarding the efficacy of these treatments in the elderly population and their tolerance profile, including the impact on quality of life, with a particular focus on the frailest subgroups, and to attempt to define the optimal treatment strategy for elderly and fragile patients (dosage and therapeutic sequence). Background: Breast cancer (BC) incidence increases with age, particularly in HR-positive/HER2-negative subtypes. Cyclin-dependent kinase 4 and 6 inhibitors (CDK 4/6is) alongside endocrine therapy (ET) have emerged as promising treatments for HR-positive/HER2-negative advanced and early BC. However, their efficacy, safety, and impact on quality of life (QoL) in older and frail patients remain underexplored. Methods: This position paper assesses the existing literature from 2015 to 2024, focusing on CDK4/6is use in patients aged 65 years and older with HR-positive/HER2-negative BC. Results: Our analysis methodically addresses critical questions regarding the utilization of CDK4/6is in the elderly BC patient population, organizing findings from the metastatic and adjuvant settings. In the metastatic setting, CDK4/6is significantly improve progression-free survival (PFS), paralleling benefits observed in younger patients, and suggest potential overall survival (OS) benefits, warranting further investigation. Despite an increased incidence of grade ≥ 3 adverse events (AEs), such as neutropenia and asthenia, CDK4/6is present a markedly lower toxicity profile compared to traditional chemotherapy, with manageable side effects. QoL analysis indicates that integrating CDK4/6is into treatment regimens does not significantly impact elderly BC patients' daily life and symptom management. Special attention is given to frail subgroups, and personalized approaches are recommended to balance efficacy and adverse effects, such as starting with ET alone and introducing CDK4/6is upon progression in patients with a low disease burden. Transitioning to the adjuvant setting, early results, particularly with abemaciclib, indicate positive effects on disease-free survival (DFS), emphasizing the need for continued analysis to validate these findings and assess long-term implications. However, data on older patients are insufficient to conclude whether they truly benefit from this treatment. Conclusion: Overall, CDK4/6is present a favorable benefit-risk profile in older BC patients, at least in advanced BC; however, further research is warranted to optimize treatment strategies and improve outcomes in this population [ABSTRACT FROM AUTHOR]

Simple Summary: This study aims to define and calculate several specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters included the ratio of specimen volume to tumor volume with different optimum margin widths (edges containing healthy tissue) and the tumor eccentricity, which is a measure for how centrally the tumor is located in the excised specimen. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume got excised, respectively. The median tumor eccentricity was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). These parameters could be used to compare surgical accuracy when evaluating new technologies for intraoperative BCS guidance in the future. This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity [maximum tumor-margin distance − minimum tumor-margin distance] and the relative tumor eccentricity [tumor eccentricity ÷ pathological tumor diameter] were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance. [ABSTRACT FROM AUTHOR]

Psychological distress persists amongst breast cancer survivors, so reliable assessment of symptoms is essential. The Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) is a composite measure of depression and anxiety and has been used to measure distress. This study aimed to evaluate the psychometric properties of the PHQ-ADS within breast cancer survivors. Breast cancer survivors (N = 280) were recruited online and followed up at 12-months. Depression (PHQ-8) and anxiety (GAD-7) items formed the composite PHQ-ADS score. Additional measures included: distress thermometer (convergent validity), fear of cancer recurrence and COVID distress (discriminant validity), and self-compassion (predictive validity). Confirmatory factor analysis (CFA) using weighted least squares mean and variance adjusted estimation was undertaken. One, two, and bifactor models underlying the PHQ-ADS were evaluated. The bifactor model had the most appropriate model fit overall. Omega hierarchical for the general distress factor was 0.914, accounting for 82% of explained variance. This suggests the PHQ-ADS is sufficiently unidimensional to warrant use of a total composite score. The PHQ-ADS demonstrated strong convergent and moderate discriminant validity. Self-compassion was an independent predictor of distress at 12-months. The PHQ-ADS is a valid measure for psychological distress in breast cancer survivors prescribed hormone therapy. • The PHQ-ADS shows good psychometric properties in breast cancer survivors. • Sufficient unidimensionality shown, suggesting suitability of total distress score. • The PHQ-ADS shows good convergent validity and adequate discriminant validity. • Self-compassion explained 7% unique variance in distress at 12 months. [ABSTRACT FROM AUTHOR]

For second ipsilateral breast tumor event (2ndIBTE), conservative treatment (CT) involving wide local excision plus accelerated partial breast reirradiation (APBrI) is increasingly used as an alternative to mastectomy. This study investigates the impact of APBrI technique and multicatheter interstitial high dose-rate brachytherapy (MIB) dosimetry parameters on toxicity and survival in patients with 2ndIBTE. Data from patients with 2ndIBTE treated with CT, were analyzed. Inclusion criteria specified 2ndIBTE occurring at least one year after 1st CT for primary breast cancer. Treatment details and dosimetry parameters were recorded. Primary endpoint was late toxicity. Secondary endpoints were late toxicity prognostic factors analysis and oncological outcome. From 07/2005 and 07/2023, 201 patients (pts) received 2nd CT. With a median follow-up of 49.6 months (44.9–59.5), tumor size was less than 2 cm (88.1%), with estrogen receptor positive (92.7%). Patients were low (63.7%) or intermediate (29.8%) GEC-ESTRO APBI risk classification. Late toxicities were observed in 34.8% (G1 52.3%, G2 40.7%). Cutaneous fibrosis was the most common toxicity. Cosmetic outcomes were excellent in 64.1%. Dosimetry analysis revealed positive correlations between complications and absolute volumes of CTV, V100, V150, and V200. Volumes requiring higher needle number and lower DNR resulted in fewer complications. 5-year disease-free and overall survival were 88% and 95% respectively. Second CT for 2ndIBTE showed favorable oncological outcomes and survival rates. Complications were correlated with specific dosimetric parameters, emphasizing the importance of tailored treatment planning. This study provides valuable insights in risk stratification and MIB optimization for APBrI. [ABSTRACT FROM AUTHOR]

Simple Summary: The current evidence regarding Indigenous* women and breast cancer in Australia shows lower prevalence but higher mortality rates. There are a range of reasons for this, including co-morbidities, lack of access to health services and low health information fluency. Perhaps most importantly, breast cancer health policy and service delivery practice do not meet the needs of Indigenous women in Australia, according to Indigenous women. Talking and listening to Indigenous women about breast cancer highlight that the solutions to improve breast cancer outcomes are available and that they are not complex. Indigenous women must be involved in the improvement of policy and practice in order for these outcomes to improve. *Terminology: We respectfully refer to Aboriginal and Torres Strait Islander people as "Indigenous". In Australia, the incidence rate of breast cancer is lower in Indigenous* women than non-Indigenous women; however, the mortality rate is higher, with Indigenous women 1.2 times more likely to die from the disease. This paper provides practical and achievable solutions to improve health outcomes for Indigenous women with breast cancer in Australia. This research employed the Context–Mechanism–Outcome (CMO) framework to reveal potential mechanisms and contextual factors that influence breast cancer outcomes for Indigenous women, stratified into multiple levels, namely, micro (interpersonal), meso (systemic) and macro (policy) levels. The CMO framework allowed us to interpret evidence regarding Indigenous women and breast cancer and provides nine practical ways to improve health outcomes and survival rates. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer is a heterogenous disease from many aspects. The most common special-type, invasive lobular carcinoma, is not homogenous either. It may have several mammographic appearances, some of which make screen detection difficult. Histologically, lobular carcinoma has a peculiar morphology consisting of non-cohesive cells often arranged in single file, but this classical morphology may often be admixed with less easily recognizable histological patterns, such as the solid, the alveolar, the trabecular, or the tubule-forming, some of which are characterized by the regained cohesion of the tumor cells. Whether the dominant histological patterns are associated with specific mammographic presentation is not known, but such associations may be important from diagnostic aspects looking at radio-pathological correlations. It was believed that the classical histologic pattern might be more often occult, whereas more cohesive or dense patterns might be more often mass forming. Our analysis failed to demonstrate obvious associations between radiological and pathological presentations. Invasive lobular carcinoma of the breast has different mammographic appearances, including spiculated or lobulated masses, architectural distortion, increased breast density, and the possibility of also being occult. Histologically, the morphology is also variable, as several patterns have been described beside the classical one, including the solid, the alveolar, the trabecular, the one with tubular elements, and others. Of 146 ILC cases, 141 were reviewed for mammographic appearance and 136 for histological patterns by two radiologist and two pathologists, respectively; 132 common cases were analyzed for possible associations between mammographic presentation and the histological patterns. Interobserver agreement on the presence or absence of a given mammographic morphology ranged from 45% (increased density) to 95% (occult lesion); the most common radiomorphology was that of a spiculated mass. Interobserver agreement on the presence or absence of a given histological pattern ranged between 79% (solid) and 99% (classical) but was worse when semi-quantification was also included. The mammography–pathology correlation was less than optimal. Multifocality was more commonly detected by histology. The identification of a mammographic mass lesion often coincided with a mass-like lesion on the histological slides and vice versa, but nearly half of the mammographically occult lesions were felt to have masses on histological slides assessed grossly. Histological patterns showed no obvious associations with one or the other mammographic appearance. [ABSTRACT FROM AUTHOR]

Two recent reports identify ZNF703 as an oncogene driving selection of frequent chromosome 8p12 amplifications in luminal B breast tumors. The estrogen-responsive ZNF703 gene encodes a transcriptional cofactor that, when overexpressed, induces cell proliferation and interferes with transforming growth factor beta signaling. In MCF7 cells, increased ZNF703 expression results in activation of genes involved in stem cell self-renewal - while in primary human mammary epithelial cells, ZNF703 increases the ratio of luminal to basal progenitors. Expression of the murine homolog of ZNF703 reduces cell adhesion and promotes metastasis. ZNF703 overexpression thus alters regulation of proliferation and differentiation in luminal B tumors.

Simple Summary: We previously showed that breast tumor tissues from women display an imbalance in abundance and composition of microbiota compared to normal healthy breast tissues. It is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The aim of our study was to conduct global metabolic profiling on normal and breast tumor tissues to identify differences in metabolite profiles and to determine whether breast microbial dysbiosis may be associated with enrichment of microbial metabolites in triple-negative breast cancer (TNBC) which disproportionately affects women of African ancestry. We observed significant correlations between elevated lipid metabolism pathways and microbial dysbiosis in TNBC tissues from both non-Hispanic black and white women. This is the first study to report an association between breast microbial dysbiosis and alterations in host metabolic pathways in breast tumors, including TNBC, of non-Hispanic black and non-Hispanic white women. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that is non-responsive to hormonal therapies and disproportionately impact women of African ancestry. We previously showed that TN breast tumors have a distinct microbial signature that differs from less aggressive breast tumor subtypes and normal breast tissues. However, it is unknown whether these differences in breast tumor microbiota may be driven by alterations in microbial metabolites, leading to potentially protective or pathogenic consequences. The goal of this global metabolomic profiling study was to investigate alterations in microbial metabolism pathways in normal and breast tumor tissues, including TNBC, of non-Hispanic black (NHB) and non-Hispanic white (NHW) women. In this study, we profiled the microbiome (16S rRNA) from breast tumor tissues and analyzed 984 metabolites from a total of 51 NHB and NHW women. Breast tumor tissues were collected from 15 patients with TNBC, 12 patients with less aggressive luminal A-type (Luminal) breast cancer, and 24 healthy controls for comparison using UHPLC-tandem mass spectrometry. Principal component analysis and hierarchical clustering of the global metabolomic profiling data revealed separation between metabolic signatures of normal and breast tumor tissues. Random forest analysis revealed a unique biochemical signature associated with elevated lipid metabolites and lower levels of microbial-derived metabolites important in controlling inflammation and immune responses in breast tumor tissues. Significant relationships between the breast microbiome and the metabolome, particularly lipid metabolism, were observed in TNBC tissues. Further investigations to determine whether alterations in sphingolipid, phospholipid, ceramide, amino acid, and energy metabolism pathways modulate Fusobacterium and Tenericutes abundance and composition to alter host metabolism in TNBC are necessary to help us understand the risk and underlying mechanisms and to identify potential microbial-based targets. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Early and complete surgical resection is the most important therapeutic and diagnostic measure. Adjuvant radiation is suggested for malign phyllode tumors, phyllode tumors larger than 10 cm or those with a low distance to the resection margins. Phyllodes tumors are rare fibroepithelial tumors of the breast. Histologically, they are usually classified as benign, borderline or malignant, though these classifications do not necessarily reflect the clinical course of the disease. These tumors may stay undetected for years, or show sudden and rapid progression. There is currently no consistent therapy recommendation based upon histological findings, the localization of the tumor and/or whether it is recurrent. Using the examples of three patients, we show how courses and therapy may differ widely, and discuss this in the context of the current state of the literature. [ABSTRACT FROM AUTHOR]

Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) is a prevalent post-translational modification (PTM) that regulates diverse cellular processes. Aberrant expression of type I PRMTs that catalyze asymmetric arginine dimethylation (ADMA) is often found in cancer, though little is known about the ADMA status of substrate proteins in tumors. Using LC-MS/MS along with pan-specific ADMA antibodies, we performed global mapping of ADMA in five patient-derived xenograft (PDX) tumors representing different subtypes of human breast cancer. In total, 403 methylated sites from 213 proteins were identified, including 322 novel sites when compared to the PhosphositesPlus database. Moreover, using peptide arrays in vitro, approximately 70% of the putative substrates were validated to be methylated by PRMT1, PRMT4, and PRMT6. Notably, when compared with our previously identified ADMA sites from breast cancer cell lines, only 75 ADMA sites overlapped between cell lines and PDX tumors. Collectively, this study provides a useful resource for both PRMT and breast cancer communities for further exploitation of the functions of PRMT dysregulation during breast cancer progression. [ABSTRACT FROM AUTHOR]

Impedance measuring acquisition systems focused on breast tumor detection, as well as image processing techniques for 3D imaging, are reviewed in this paper in order to define potential opportunity areas for future research. The description of reported works using electrical impedance tomography (EIT)-based techniques and methodologies for 3D bioimpedance imaging of breast tissues with tumors is presented. The review is based on searching and analyzing related works reported in the most important research databases and is structured according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) parameters and statements. Nineteen papers reporting breast tumor detection and location using EIT were systematically selected and analyzed in this review. Clinical trials in the experimental stage did not produce results in most of analyzed proposals (about 80%), wherein statistical criteria comparison was not possible, such as specificity, sensitivity and predictive values. A 3D representation of bioimpedance is a potential tool for medical applications in malignant breast tumors detection being capable to estimate an ap-proximate the tumor volume and geometric location, in contrast with a tumor area computing capacity, but not the tumor extension depth, in a 2D representation.

BackgroundAlthough numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.ResultsUnsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors.ConclusionMany of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.

Targeted therapy for patients with HER2‐positive (HER2+) breast cancer has improved overall survival, but many patients still suffer relapse and death from the disease. Intratumor heterogeneity of both estrogen receptor (ER) and HER2 expression has been proposed to play a key role in treatment failure, but little work has been done to comprehensively study this heterogeneity at the single‐cell level. In this study, we explored the clinical impact of intratumor heterogeneity of ER protein expression, HER2 protein expression, and HER2 gene copy number alterations. Using combined immunofluorescence and in situ hybridization on tissue sections followed by a validated computational approach, we analyzed more than 13 000 single tumor cells across 37 HER2+ breast tumors. The samples were taken both before and after neoadjuvant chemotherapy plus HER2‐targeted treatment, enabling us to study tumor evolution as well. We found that intratumor heterogeneity for HER2 copy number varied substantially between patient samples. Highly heterogeneous tumors were associated with significantly shorter disease‐free survival and fewer long‐term survivors. Patients for which HER2 characteristics did not change during treatment had a significantly worse outcome. This work shows the impact of intratumor heterogeneity in molecular diagnostics for treatment selection in HER2+ breast cancer patients and the power of computational scoring methods to evaluate in situ molecular markers in tissue biopsies.

Breast cancer, a prevalent and life-threatening disease, necessitates early detection for the effective intervention and the improved patient health outcomes. This paper focuses on the critical problem of identifying breast cancer using a model called Attention U-Net. The model is utilized on the Breast Ultrasound Image Dataset (BUSI), comprising 780 breast images. The images are categorized into three distinct groups: 437 cases classified as benign, 210 cases classified as malignant, and 133 cases classified as normal. The proposed model leverages the attention-driven U-Net's encoder blocks to capture hierarchical features effectively. The model comprises four decoder blocks which is a pivotal component in the U-Net architecture, responsible for expanding the encoded feature representation obtained from the encoder block and for reconstructing spatial information. Four attention gates are incorporated strategically to enhance feature localization during decoding, showcasing a sophisticated design that facilitates accurate segmentation of breast tumors in ultrasound images. It displays its efficacy in accurately delineating and segregating tumor borders. The experimental findings demonstrate outstanding performance, achieving an overall accuracy of 0.98, precision of 0.97, recall of 0.90, and a dice score of 0.92. It demonstrates its effectiveness in precisely defining and separating tumor boundaries. This research aims to make automated breast cancer segmentation algorithms by emphasizing the importance of early detection in boosting diagnostic capabilities and enabling prompt and targeted medical interventions. [ABSTRACT FROM AUTHOR]

Breast cancer is a type of cancer responsible for higher mortality rates among women. The cruelty of breast cancer always requires a promising approach for its earlier detection. In light of this, the proposed research leverages the representation ability of pretrained EfficientNet-B0 model and the classification ability of the XGBoost model for the binary classification of breast tumors. In addition, the above transfer learning model is modified in such a way that it will focus more on tumor cells in the input mammogram. Accordingly, the work proposed an EfficientNet-B0 having a Spatial Attention Layer with XGBoost (ESA-XGBNet) for binary classification of mammograms. For this, the work is trained, tested, and validated using original and augmented mammogram images of three public datasets namely CBIS-DDSM, INbreast, and MIAS databases. Maximum classification accuracy of 97.585% (CBIS-DDSM), 98.255% (INbreast), and 98.91% (MIAS) is obtained using the proposed ESA-XGBNet architecture as compared with the existing models. Furthermore, the decision-making of the proposed ESA-XGBNet architecture is visualized and validated using the Attention Guided GradCAM-based Explainable AI technique. [ABSTRACT FROM AUTHOR]

Breast cancers can appear and progress rapidly, necessitating more frequent monitoring outside of hospital settings to significantly reduce mortality rates. Recently, there has been considerable interest in developing techniques for portable, user-friendly, and low-cost breast tumor monitoring applications, enabling frequent and cost-efficient examinations. Microwave technique-based breast cancer detection, which is based on differential dielectric properties of malignant and healthy tissues, is regarded as a promising solution for cost-effective breast tumor monitoring. This paper presents the development process of the first proof-of-concept of a breast tumor monitoring vest which is based on the microwave technique. Two unique vests are designed and evaluated on realistic 3D human tissue phantoms having different breast density types. Additionally, the measured results are verified using simulations carried out on anatomically realistic voxel models of the electromagnetic simulations. The radio channel characteristics are evaluated and analyzed between the antennas embedded in the vest in tumor cases and reference cases. Both measurements and simulation results show that the proposed vest can detect tumors even if only 1 cm in diameter. Additionally, simulation results show detectability with 0.5 cm tumors. It is observed that the detectability of breast tumors depends on the frequency, antenna selection, size of the tumors, and breast types, causing differences of 0.5–30 dB in channel responses between the tumorous and reference cases. Due to simplicity and cost-efficiency, the proposed channel analysis-based breast monitoring vests can be used for breast health checks in smaller healthcare centers and for user-friendly home monitoring which can prove beneficial in rural areas and developing countries. [ABSTRACT FROM AUTHOR]

Aim: Neoadjuvant chemotherapy (NAC) has transitioned from a treatment modality used solely for inoperable and locally advanced breast cancer to a therapeutic approach for early-stage breast cancer. High-risk patients, such as those with HER2-positive and triple- negative breast cancer, particularly benefit from NAC. This study aimed to evaluate the factors affecting pathological complete response (pCR) in primary breast tumors and axillary lymph nodes in patients with breast cancer. Methods: The study included female patients with breast cancer who received NAC at a training and research hospital between 2020 and 2024. Patients were categorized based on age, tumor stage, and tumor biology: luminal A, HER2-positive luminal B, HER2- negative luminal B, HER2-positive alone, or triple-negative. The presence or absence of E-cadherin in tumor cells and Ki-67 levels were also examined. Data were obtained from medical records to assess the impact of these factors on complete response in patients with breast cancer and axillary metastatic lymph nodes following NAC. Results: Univariate analysis revealed that histopathological subtypes, estrogen receptor and progesterone receptor (PR) status, HER2 status, perineural invasion, lymphovascular invasion (LVI), Ki-67 index, and carcinoma in situ (CIS) component significantly influenced pCR. Multivariate analysis confirmed that PR status [Odds ratio (OR): 3.33, 95% confidence interval (CI): 1.57-7.08, p=0.002], HER2 status (OR: 3.56, 95% CI: 1.71-7.44, p=0.001), LVI (OR: 3.91, 95% CI: 1.84-8.30, p<0.001), Ki-67 index (OR: 1.03, 95% CI: 1.01-1.05, p<0.001), and CIS component (OR: 7.01, 95% CI: 2.44-20.11, p<0.001) were independent predictors of complete response. Conclusion: Our findings underscore the multifaceted nature of NAC response in breast cancer, which is influenced by histopathological and molecular characteristics. [ABSTRACT FROM AUTHOR]

Simple Summary: Improving the response of breast cancer patients by designing and applying the most appropriate treatment for each case is a major scientific challenge. Given the role of intracellular calcium in cell proliferation, apoptosis evasion and cell resistance, in this review, we discuss its potential for the development of new pharmacological treatments to treat the disease. Cancer is one of the main health problems worldwide. Only in 2020, this disease caused more than 19 million new cases and almost 10 million deaths, with breast cancer being the most diagnosed worldwide. Today, despite recent advances in breast cancer treatment, a significant percentage of patients will either not respond to therapy or will eventually experience lethal progressive disease. Recent studies highlighted the involvement of calcium in the proliferation or evasion of apoptosis in breast carcinoma cells. In this review, we provide an overview of intracellular calcium signaling and breast cancer biology. We also discuss the existing knowledge on how altered calcium homeostasis is implicated in breast cancer development, highlighting the potential utility of Ca2+ as a predictive and prognostic biomarker, as well as its potential for the development of new pharmacological treatments to treat the disease. [ABSTRACT FROM AUTHOR]

The human epidermal growth factor receptor 2 (HER2/neu) is overexpressed in 20-30% of breast cancers and is associated with tumor growth, angiogenesis, and development of distant metastases. Trastuzumab, an anti-HER2 monoclonal antibody, is used for the treatment of HER2 positive breast cancer and clinical efficacy of this agent is dependent on HER2 expression. Targeted PET imaging of HER2 with radiolabeled trastuzumab may be used to determine HER2 expression levels and guide therapy selection. The purpose of the current study was to evaluate a facile 89Zr-trastuzumab preparation method that can be efficiently applied for clinical grade production. Also, relative HER2 expression levels in orthotopic and metastatic breast cancer models were assessed by PET imaging using the 89Zr-trastuzumab produced by this simpler method.

Histone deacetylase (HDAC) inhibitors impair tumor cell proliferation and alter gene expression. However, the impact of these changes on anti-tumor immunity is poorly understood. Here, we showed that the class I HDAC inhibitor, entinostat (ENT), promoted the expression of immune-modulatory molecules, including MHCII, costimulatory ligands, and chemokines on murine breast tumor cells in vitro and in vivo. ENT also impaired tumor growth in vivo—an effect that was dependent on both CD8+ T cells and IFNγ. Moreover, ENT promoted intratumoral T-cell clonal expansion and enhanced their functional activity. Importantly, ENT sensitized normally unresponsive tumors to the effects of PD1 blockade, predominantly through increases in T-cell proliferation. Our findings suggest that class I HDAC inhibitors impair tumor growth by enhancing the proliferative and functional capacity of CD8+ T cells and by sensitizing tumor cells to T-cell recognition. [ABSTRACT FROM AUTHOR]

Antigen recognition by MHC class I molecules is a key step for the initiation of the immune response. We hypothesized that expression of these molecules could be a marker of immune-activated breast cancers. Data from KM Plotter were extracted to develop an exploratory cohort. Information from Cancer Genome Atlas (TCGA) and METABRIC was used to create two validation cohorts. Raw data were re-processed and analyzed using plyr R and Bioconductor. We predicted epitope-HLA binding to MHC I molecules by using NetMHC 4.0. Cox proportional hazards regression was computed to correlate gene expression and survival outcome. There was a weak but positive correlation between mutational burden and the expression of most MHC class I molecules. In the exploratory cohort, expression of HLA-A and HLA-B was associated with favorable relapse-free survival (RFS) and overall survival (OS) in the basal-like subgroup. This was confirmed in the METABRIC and TCGA dataset. Expression of HLA-A and HLA-B was associated with biomarkers of T cell activation (GZMA, GZMB, and PRF1) and improved the predictive capacity of known immunologic signatures. Several neopeptides expressed in breast cancer were also identified including FUK, SNAPC3, GC, ANO8, DOT1L, HIST1H3F, MYBPH, STX2, FRMD6, CPSF1, or SMTN, among others. Expression of HLA A and B is associated with T cell activation and identifies immune activated, basal-like breast cancers with favorable prognosis. Antigen recognition markers should be incorporated into the assessment of the tumor immune state of basal-like breast patients. [ABSTRACT FROM AUTHOR]

To investigate the difference in texture features on diffusion weighted imaging (DWI) images between breast benign and malignant tumors. Patients including 56 with mass-like breast cancer, 16 with breast fibroadenoma, and 4 with intraductal papilloma of breast treated in the Hainan Hospital of Chinese PLA General Hospital were retrospectively enrolled in this study, and allocated to the benign group (20 patients) and the malignant group (56 patients) according to the post-surgically pathological results. Texture analysis was performed on axial DWI images, and five characteristic parameters including Angular Second Moment (ASM), Contrast, Correlation, Inverse Difference Moment (IDM), and Entropy were calculated. Independent sample t-test and Mann-Whitney U test were performed for intergroup comparison. Regression model was established by using Binary Logistic regression analysis, and receiver operating characteristic curve (ROC) analysis was carried out to evaluate the diagnostic efficiency. The texture features ASM, Contrast, Correlation and Entropy showed significant differences between the benign and malignant breast tumor groups (P ASM =0.014, P contrast =0.019, P correlation =0.010, P entropy =0.007). The area under the ROC curve was 0.685, 0.681, 0.754, and 0.683 respectively for the positive texture variables mentioned above, and that for the combined variables (ASM, Contrast, and Entropy) was 0.802 in the model of Logistic regression. Binary Logistic regression analysis demonstrated that ASM, Contrast and Entropy were considered as the specific imaging variables for the differential diagnosis of breast benign and malignant tumors. The texture analysis of DWI may be a simple and effective tool in the differential diagnosis between breast benign and malignant tumors. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy among women, and early diagnosis and targeted therapy have garnered significant attention. Non-coding RNAs have emerged as potential diagnostic, prognostic, and treatment biomarkers for breast cancer. This study aimed to evaluate the expression of non-coding RNAs, specifically miR-506 and circular RNA 000284, and their target gene SNAIL-2 in breast cancer patients compared to normal controls. The study also focused on clinicopathological characteristics, and plasma was monitored for expression of circ0000284 to identify a possible accessible cancer-related marker. Methods: Using the SYBR-Green Real-time PCR technique, circ0000284, miR-506, and SNAIL2 expression were analyzed in total RNA extracted from 80 breast tumors compared with normal control. Also, the expression of circ0000284 was monitored in the plasma of breast cancer patients. The association of circ0000284, miR-506, and SNAIL2 expression with clinicopathological characteristics were studied. Results: The results showed overexpression, down-regulation, and up-regulation of circRNA 000284, miR-506, and SNAIL-2, respectively. These expression changes were associated with advanced stages of the disease and lymph nodal involvement, which are signs of a poor prognosis (<0. 0001). Additionally, a positive direct correlation was observed between circRNA000284 expression in tumors and plasma (<0. 0001). Moreover, it was discovered that circ-0000284 sponged miR-506, causing up-regulation of SNAIL-2 as its mRNA target. Conclusion: The upregulation of SNAIL-2 as an epithelial-mesenchymal-transition (EMT) factor leads to poor prognosis in breast cancer and is epigenetically regulated by miR-506 and circRNA 000284. Therefore, the overexpression of circR- NA000284 in plasma could be considered an indicator of lymph nodal involvement and advanced stages of cancer, and nominated as a poor prognostic biomarker for future considerations. [ABSTRACT FROM AUTHOR]

Introduction Oncoplastic techniques expanded the spectrum of breast conservative surgery for the management of early breast cancer. Planning for resection of medial breast tumors is difficult. The scars are apparent and deformity is eminent. Mammaplasty techniques do not leave scars in the medial area and reshaping can avoid deformity. Aim The study was carried out to evaluate the use of superior lateral pedicle and its inferior extension to fill the medial defects that occur after resection of medial breast tumors exploring the technical issues and results in terms of resection volume, adequacy of resection, deformity, complications, and esthetic results. Patients and methods Thirty consecutive patients with early breast cancer and medial tumors underwent wide excision to negative margins followed by reconstruction of defects using the extended superior lateral pedicle technique. Results All cases had negative resection margins. The weight of the specimen ranged from 65 to 565 g with an average weight of 262.47±165.31 g. Complications occurred in eight patients. No major complications or nipple loss occurred. Esthetic results were considered very good to excellent by both surgeons and patients. Conclusion Oncoplastic techniques for medial breast quadrants enabled wide resection, achieved adequate resection to negative margins with minimal complication rates and favorable esthetic results. [ABSTRACT FROM AUTHOR]

Abstract Background Obesity increases breast cancer (BC) risk in post-menopausal women by mostly unknown molecular mechanisms which may partly be regulated by microRNAs (miRNAs). Methods We isolated RNA from paired benign and malignant biopsies from 83 BC patients and determined miRNA profiles in samples from 12 women at the extremes of the BMI distribution by RNA-seq. Candidates were validated in all samples. Associations between miR-10b expression and validated target transcript levels, and effects of targeted manipulation of miR-10b levels in a primary BC cell line on proliferation and invasion potential, were explored. Results Of the 148 miRNAs robustly expressed in breast tissues, the levels of miR-21, miR-10b, miR-451a, miR-30c, and miR-378d were significantly associated with presence of cancer. Of these, miR-10b showed a stronger down-regulation in the tumors of the obese subjects, as opposed to the lean. In ductal but not lobular tumors, significant inverse correlations were observed between the tumor levels of miR-10b and miR-30c and the mRNA levels of cancer-relevant target genes SRSF1, PIEZO1, MAPRE1, CDKN2A, TP-53 and TRA2B, as well as tumor grade. Suppression of miR-10b levels in BT-549 primary BC–derived cells increased cell proliferation and invasive capacity, while exogenous miR-10b mimic decreased invasion. Manipulation of miR-10b levels also inversely affected the mRNA levels of miR-10b targets BCL2L11, PIEZO1 and NCOR2. Conclusions Our findings suggest that miR-10b may be a mediator between obesity and cancer in post-menopausal women, regulating several known cancer-relevant genes. MiR-10b expression may have diagnostic and therapeutic implications for the incidence and prognosis of BC in obese women.

Breast cancer cells modulate lipid and fatty acid metabolism to sustain proliferation. The role of adipocytes in cancer treatment efficacy remains, however, to be fully elucidated. We investigated whether diet-induced obesity (DIO) affects the efficacy of doxorubicin treatment in a breast tumor-bearing mouse model. Female C57BL6 mice were fed a high fat or low fat diet for the full duration of the study (12 weeks). After 8 weeks, mice were inoculated with E0771 triple-negative breast cancer cells in the fourth mammary gland to develop breast tumor allographs. Tumor-bearing mice received either vehicle (Hank's balanced salt solution) or doxorubicin (chemotherapy). Plasma inflammatory markers, tumor, and mammary adipose tissue fatty acid composition, as well as protein expression of lipid metabolism markers were determined. The high fat diet (HFD) attenuated the treatment efficacy of doxorubicin. Both leptin and resistin concentrations were significantly increased in the HFD group treated with doxorubicin. Suppressed lipogenesis (decreased stearoyl CoA-desaturase-1) and lipolysis (decreased hormone-sensitive lipase) were observed in mammary adipose tissue of the DIO animals, whereas increased expression was observed in the tumor tissue of doxorubicin treated HFD mice. Obesogenic conditions induced altered tissue fatty acid (FA) compositions, which reduced doxorubicin's treatment efficacy. In mammary adipose tissue breast cancer cells suppressed the storage of FAs, thereby increasing the availability of free FAs and favored inflammation under obesogenic conditions.

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Abstract Background Approximately one in five breast cancers are driven by amplification and overexpression of the human epidermal growth factor receptor 2 (HER2) receptor kinase, and HER2-enriched (HER2E) is one of four major transcriptional subtypes of breast cancer. We set out to understand the genomics of HER2 amplification independent of subtype, and the underlying drivers and biology of HER2E tumors. Methods We investigated published genomic data from 3155 breast tumors and 5391 non-breast tumors. Results HER2 amplification is a distinct driver event seen in all breast cancer subtypes, rather than a subtype marker, with major characteristics restricted to amplification and overexpression of HER2 and neighboring genes. The HER2E subtype has a distinctive transcriptional landscape independent of HER2A that reflects androgen receptor signaling as replacement for estrogen receptor (ER)-driven tumorigenesis. HER2 amplification is also an event in 1.8% of non-breast tumors. Conclusions These discoveries reveal therapeutic opportunities for combining anti-HER2 therapy with anti-androgen agents in breast cancer, and highlight the potential for broader therapeutic use of HER2 inhibitors.

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.

Background and purpose: Breast cancer is the most common type of cancer in women and the second cause of cancer death in Iran. Widespread use of mammography and sonography could increase survival in patients with early detection. Sensitivity and specificity of mammography and sonography are different in various sources. This study aimed at assessing the concordance of mammography-sonography reports with pathology reports in tumor size among patients with breast cancer. Materials and methods: This research studied 100 women with pathologically proven invasive breast cancer attending Ramsar Imam Sadjad Hospital, 2016-2017. The concordance of mammography-sonography reports with pathology report was studied. Pearson correlation coefficient was applied to investigate the correlations. Results: The mean age of the patients was 48±7.45. Most of them were married with history of labor and breastfeeding. Many patients had BMI>25. In most cases left breast and external upper quadrant were involved and most tumors had ductal pathology. The correlation coefficient between tumor size in mammography and pathology was 0.80 (p

Background & Objectives: lnc-CCAT2 is a non-protein coding RNA, which is highly expressed in tissues and cancer cell types. Due to the increasing incidence of breast tumors in recent years, in this research, the qualification of CCAT2 gene expression is assessed as a potential molecular marker in the diagnosis and treatment of breast tumors. Material & Methods: Totally, 35 breast tumor specimens and 35 non-tumoral ones related to the tumor margins were studied using quantitative real-time PCR method. Gene β2m was used as the internal control. Obtained results were statistically analyzed Using the SPSS and sigmaplot software. Results: The results showed that CCAT2 gene expression, significantly increased in breast tumor samples compared to marginal non-tumor specimens. (P < 0.01) Conclusion: This results showed that CCAT2 gene can be applied as a diagnostic marker for the identification and diagnosis of breast tumor tissues and non-tumor types. Therefore, it can be used alongside other conventional Diagnostic Laboratorial methods. More studies are underway on the biomarking potentiality of this gene.