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This paper presents a prototype of a portable and modular electrical impedance tomography (EIT) system for breast tumor detection. The proposed system uses MATLAB to generate three-dimensional representations of breast tissue. The modular architecture of the system allows for flexible customization and scalability. It consists of several interconnected modules. Each module can be easily replaced or upgraded, facilitating system maintenance and future enhancements. Testing of the prototype has shown promising results in preliminary screening based on experimental studies. Agar models were used for the experimental stage of this project. The 3D representations provide clinicians with valuable information for accurate diagnosis and treatment planning. Further research and refinement of the system is warranted to validate its performance in future clinical trials. [ABSTRACT FROM AUTHOR]

Objective: We explored the role of maximum intensity projection (MIP) based on high frame rate contrast-enhanced ultrasound (H-CEUS) for the differentiation of breast tumors. Methods: MIP imaging was performed in patients with breast tumors who underwent H-CEUS examinations. The microvasculature morphology of breast tumors was assessed. The receiver operating characteristic curve was plotted to evaluate the diagnostic performance of MIP. Results: Forty-three breast tumors were finally analyzed, consisting of 19 benign and 24 malignant tumors. For the =30-s and >30-s phases, dot-, line-, or branch-like patterns were significantly more common in benign tumors. A tree-like pattern was only present in the benign tumors. A crab claw-like pattern was significantly more common in the malignant tumors. Among the tumors with crab claw-like patterns, three cases of malignant tumors had multiple parallel small spiculated vessels. There were significant differences in the microvasculature morphology for the =30-s and >30-s phases between the benign and malignant tumors (all p < 0.001). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the =30-s phase were all higher than those of the >30-s phase for the classification of breast tumors. Conclusion: MIP based on H-CEUS can be used for the differentiation of breast tumors, and the =30-s phase had a better diagnostic value. Multiple parallel small spiculated vessels were a new finding, which could provide new insight for the subsequent study of breast tumors. [ABSTRACT FROM AUTHOR]

Breast carcinoma is the most common cancer in women. Nineteen different subtypes of breast carcinomas are recognized in the current WHO classification of breast tumors. Except for these subtypes, there are a number of carcinomas with special morphologic and immunohistochemical features that are not included in the 5th WHO classification, while others are considered special morphologic patterns of invasive breast carcinoma of no special type. In this manuscript, we systematically review the literature on four different subtypes of invasive breast carcinoma, namely lymphoepithelioma-like breast carcinoma, breast carcinoma with osteoclast-like giant cells, signet-ring breast carcinoma, and metaplastic breast carcinoma with melanocytic differentiation. We describe their clinicopathological characteristics, focusing on the differential diagnosis, treatment, and prognosis. [ABSTRACT FROM AUTHOR]

A recent study found that the activation of the glucocorticoid receptor (GR) leads to the upregulation of the ZBTB16 gene in breast cancer, specifically in luminal A tumors. The study suggests that ZBTB16 functions as a hormone-driven factor that limits the growth and progression of luminal breast cancer. The study also found that estrogen receptor (ER)-positive and progesterone receptor (PR)-positive breast tumors have higher levels of NR3C1 (gene encoding GR) expression compared to ER-negative and PR-negative tumors. Additionally, the study found that ZBTB16 expression is higher in ER-positive and PR-positive tumors compared to ER-negative and PR-negative tumors. These findings suggest that high expression of both NR3C1 and ZBTB16 is associated with the luminal A subtype of breast cancer and may contribute to a better prognosis in this patient group. [Extracted from the article]

Objective: Neuroendocrine neoplasms of primary breast tumors are rare compared to locations, such as the respiratory system and gastrointestinal system, where they are frequently observed. The diagnostic criteria for primary neuroendocrine tumors of the breast have been changed since first description. Morphological and immunohistochemical features helpful in their diagnosis, which vary due to the heterogeneous nature of these tumors, are highlighted in this retrospective study. The purpose was to determine specific histopathological features that can identify neuroendocrine morphology in primary breast tumors. Materials and Methods: Cases diagnosed with invasive breast carcinoma from resection materials in a single center between 2011 and 2022 and in which neuroendocrine markers were investigated were included. Demographic information, initial histopathological diagnosis, presence of tumor in another organ, tumor location, size and surgical details of the cases were obtained from the hospital database and pathology reports. The slides were re-evaluated in terms of tumor growth pattern, cribriformity, tubule formation, nuclear features, prominence of nucleoli, palisading and basal location of nuclei, presence of grooves, cytoplasmic features and evidence of cytoplasmic border. Results: The presence of basally located nuclei, absence of tubule formation, inconspicuous nucleoli, fine nuclear chromatin, granular cytoplasm and inconspicuous cytoplasmic borders were frequent findings in tumors with neuroendocrine features (p<0.05). These features may help differentiate primary breast tumors with neuroendocrine features from other breast carcinomas. Conclusion: The histopathological features that are different from the specific features seen in classical neuroendocrine tumors, the absence of specific clinical and radiological findings, the inability to study neuroendocrine markers in every laboratory and the need to prove that the breast tumor is not a metastasis all create diagnostic difficulties for primary breast neuroendocrine neoplasms. We believe that the results of this study may help diagnose and identify more specific histomorphological features that help determine neuroendocrine morphology in primary breast tumors. [ABSTRACT FROM AUTHOR]

Breast radiologists encounter unusual lesions, which may not be well described in the literature. Previously based on histologic and molecular classifications, the World Health Organization (WHO) classification of tumors has become increasingly multidisciplinary. Familiarity with imaging features and basic pathology of infrequent breast lesions, as well as their current classification according to the WHO, may help the radiologist evaluate biopsy results for concordance and help direct the management of uncommon breast lesions. This review article provides a case-based review of imaging features and WHO histologic classification of rare breast tumors. [ABSTRACT FROM AUTHOR]

The purpose of this study was to fuse conventional radiomic and deep features from digital breast tomosynthesis craniocaudal projection (DBT-CC) and ultrasound (US) images to establish a multimodal benign-malignant classification model and evaluate its clinical value. Data were obtained from a total of 487 patients at three centers, each of whom underwent DBT-CC and US examinations. A total of 322 patients from dataset 1 were used to construct the model, while 165 patients from datasets 2 and 3 formed the prospective testing cohort. Two radiologists with 10–20 years of work experience and three sonographers with 12–20 years of work experience semiautomatically segmented the lesions using ITK-SNAP software while considering the surrounding tissue. For the experiments, we extracted conventional radiomic and deep features from tumors from DBT-CCs and US images using PyRadiomics and Inception-v3. Additionally, we extracted conventional radiomic features from four peritumoral layers around the tumors via DBT-CC and US images. Features were fused separately from the intratumoral and peritumoral regions. For the models, we tested the SVM, KNN, decision tree, RF, XGBoost, and LightGBM classifiers. Early fusion and late fusion (ensemble and stacking) strategies were employed for feature fusion. Using the SVM classifier, stacking fusion of deep features and three peritumoral radiomic features from tumors in DBT-CC and US images achieved the optimal performance, with an accuracy and AUC of 0.953 and 0.959 [CI: 0.886–0.996], a sensitivity and specificity of 0.952 [CI: 0.888–0.992] and 0.955 [0.868–0.985], and a precision of 0.976. The experimental results indicate that the fusion model of deep features and peritumoral radiomic features from tumors in DBT-CC and US images shows promise in differentiating benign and malignant breast tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: HER2-low breast cancer is a newly recognized subtype that has shown promising responses to treatment with antibody–drug conjugates (ADCs). However, there is still little known about its clinical and molecular characteristics. In this study, we examined the clinical and pathological features, survival rates, and expression of HER2-related genes in Colombian patients with HER2-low breast cancer, comparing them to HER2-negative and positive groups. We found that HER2-low tumors were better differentiated and had a lower proliferation index compared to HER2-positive tumors. Additionally, compared to HER2-negative cases, HER2-low patients had higher mRNA expression of the ERBB2 gene and longer overall survival rates. Despite these findings, there were no significant differences in survival when adjusted for estrogen receptor status and clinical stage. These results highlight the need for further research on HER2-low breast cancer to optimize treatment strategies for this unique group. HER2-low tumors have shown promise in response to antibody–drug conjugates (ADCs) in recent clinical trials, underscoring the need to characterize this group's clinical phenotype. In this study, we aimed to explore the clinicopathological features, survival rates, and HER2 amplicon mRNA expression of women affected with HER2-low breast cancer, compared with HER2-negative and HER2-positive groups. We included 516 breast cancer patients from Colombia, for whom we compared clinicopathological features, mRNA expression of three HER2 amplicon genes (ERBB2, GRB7 and MIEN1), survival and risk of mortality between HER2-low cases (1+ or 2+ with negative in situ hybridization (ISH) result) with HER2-positive (3+ or 2+ with positive ISH test) and HER2-negative (0+) cases. A higher proportion of patients with better-differentiated tumors and a lower proliferation index were observed for HER2-low tumors compared to the HER2-positive group. Additionally, HER2-low tumors showed higher mRNA expression of the ERBB2 gene and longer overall survival rates compared to HER2-negative cases. Nonetheless, a Cox-adjusted model by ER status and clinical stage showed no statistically significant differences between these groups. Our results show differences in important clinicopathological features between HER2-low and both HER2-positive and negative tumors. Given this unique phenotype, it is crucial to evaluate the potential advantages of ADC therapies for this emerging subtype of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Beckwith–Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression. Case presentation: A 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected. Conclusions: In this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer among women, and ultrasound is a usual tool for early screening. Nowadays, deep learning technique is applied as an auxiliary tool to provide the predictive results for doctors to decide whether to make further examinations or treatments. This study aimed to develop a hybrid learning approach for breast ultrasound classification by extracting more potential features from local and multi-center ultrasound data. Methods: We proposed a hybrid learning approach to classify the breast tumors into benign and malignant. Three multi-center datasets (BUSI, BUS, OASBUD) were used to pretrain a model by federated learning, then every dataset was fine-tuned at local. The proposed model consisted of a convolutional neural network (CNN) and a graph neural network (GNN), aiming to extract features from images at a spatial level and from graphs at a geometric level. The input images are small-sized and free from pixel-level labels, and the input graphs are generated automatically in an unsupervised manner, which saves the costs of labor and memory space. Results: The classification AUCROC of our proposed method is 0.911, 0.871 and 0.767 for BUSI, BUS and OASBUD. The balanced accuracy is 87.6%, 85.2% and 61.4% respectively. The results show that our method outperforms conventional methods. Conclusions: Our hybrid approach can learn the inter-feature among multi-center data and the intra-feature of local data. It shows potential in aiding doctors for breast tumor classification in ultrasound at an early stage. [ABSTRACT FROM AUTHOR]

Conventional benign tumor excision leaves scars on the skin surface of the breast, which is unacceptable for young patients. The feasibility and clinical results of endoscopic resection of benign breast tumors through a single axillary incision via an inflatable method were evaluated. Methods: Clinicopathological data from 62 patients who underwent this procedure from June 2022 to July 2023 were retrospectively collected. The surgical success rate, number of tumors excised, operative time, intraoperative conditions, postoperative complications, and clinical outcomes were analyzed. Results: A total of 144 benign tumors were resected, and the surgical success rate was 100% (62/62). The time required to resect tumors located in the inner quadrant with larger diameters was shorter than the time to resect tumors located in the outer quadrant with smaller tumors. Sixty-two patients experienced reduced intraoperative bleeding and did not experience skin burns, incision infections, or poor healing. However, all patients experienced varying degrees of subcutaneous emphysema during the postoperative period. Fourteen patients experienced minor local effusions, and 3 patients experienced mild upper limb dysfunction, which resolved within one month. During the six-month follow-up period, there were no cases of tumor recurrence or new tumors. The ABNSW score was above 14 points, and patient satisfaction was high. Conclusion: Endoscopic resection of benign breast tumors through a single incision in the axilla via the inflatable method could quickly remove lesions larger than 3.0 cm. This method also results in hidden scars and good cosmetic effects on the shape of the breast. This is a new and effective treatment for benign breast tumors. Trial registration: This retrospective study was registered in the National Medical Research Registry filing system (https://www.medicalresearch.org.cn) (No. MR-44–22-007981) and recorded in the Medical Research Division of our hospital (No. NYXJS-22–021). [ABSTRACT FROM AUTHOR]

Background: Breast cancer, the most prevalent cancer in women and the second leading cause of cancer-related deaths worldwide, is a complex and heterogeneous disease characterized by multiple tumor types with distinct tissue patterns, biological characteristics, and clinical behaviors. Given the critical role of histopathological and molecular characteristics in the treatment and management of breast cancer. Objectives: This study was undertaken to investigate the histopathological and molecular characteristics of malignant breast masses in the city of Sanandaj from 2019 to 2021. Methods: In this descriptive-analytical study, out of 1,631 pathology reports from breast tissue samples collected in Sanandaj, a city in northwest Iran, between 2019 and 2021, 597 (36%) malignant cases were examined for their pathological type and molecular characteristics. Data analysis was performed using SPSS 26 software, employing chi-square and Fisher's exact tests. Results: The mean age of the patients at diagnosis was 49.7 ± 11.9 years. The most prevalent molecular subtype was luminal A (56.4%), followed by triple-negative (16.7%), human epidermal growth factor receptor 2 (HER2)-positive/enriched (14.1%), and luminal B (14%). Invasive ductal carcinoma was the predominant histological type, accounting for 82.7% of cases, followed by lobular invasive carcinoma (8.2%). Papillary carcinoma accounted for 5.9% of cases, metaplastic carcinoma for 1.8%, and mucinous carcinoma for 1.3%. Higher grades at the time of diagnosis were associated with the metaplastic subtype (P < 0.001). The only biomarker that showed a significant association with pathological types of breast cancer was Ki-67. The percentage of cases positive for Ki-67 was higher in three types of breast cancer: Infiltrating ductal carcinoma, metaplastic, and papillary (intraductal) carcinoma, compared to the other types (P < 0.001). Conclusions: According to our data, infiltrating ductal carcinoma is the most prevalent pathological type, and luminal A is the most common molecular subtype among Kurdish women in Iran. It is recommended that future studies examine patient survival based on the pathological and molecular types of tumors, including the evaluation of additional biomarkers. Furthermore, comparing these results with those from other ethnic groups could provide valuable insights into the impact of ethnicity on breast cancer characteristics and outcomes. [ABSTRACT FROM AUTHOR]

Background: To evaluate the technical success and patient safety of magnetic resonance-guided percutaneous microwave coagulation (MR-guided PMC) for breast malignancies. Methods: From May 2018 to December 2019, 26 patients with breast tumors measuring 2 cm or less were recruited to participate in a prospective, single-institution clinical study. The primary endpoint of this study was the evaluation of treatment efficacy for each patient. Histochemical staining with α-nicotinamide adenine dinucleotide and reduced (NADH)-diaphorase was used to determine cell viability following and efficacy of PMC. The complications and self-reported sensations from all patients during and after ablation were also assessed. The technical success of the PMC procedure was defined when the area of the NADH-diaphorase negative region fully covered the hematoxylin–eosin (H&E) staining region in the tumor. Results: All patients had a complete response to ablation with no residual carcinoma on histopathological specimen. The mean energy, ablation duration, and procedure duration per tumor were 36.0 ± 4.2 kJ, 252.9 ± 30.9 S, and 104.2 ± 13.5 min, respectively. During the ablation, 14 patients underwent prolonged ablation time, and 1 patient required adjusting of the antenna position. Eleven patients had feelings of subtle heat or swelling, and 3 patients experienced slight pain. After ablation, one patient took two painkillers because of moderate pain, and no patients had postoperative oozing or other complications after PMC. Induration around the ablation area appeared in 16 patients. Conclusion: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. Critical relevance statement: MR-guided PMC of small breast tumors is feasible and could be applied in clinical practice in the future. Key points: • MR-guided PMC of small breast tumors is feasible. • PMC was successfully performed for all patients. • All patients were satisfied with the final cosmetic result. [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the effects of BP and doxorubicin (DOX) on 4T1 tumor cells in a mouse model. Materials and Methods: After inducing breast tumors, 70 4T1-tumor-bearing BALB/c mice were divided into seven groups (n = 10/group). The groups were treated with DOX and BP for 35 days. On the 36th day, blood was taken from the heart, and serum was separated to measure levels of cytokines, estrogen, progesterone, testosterone, and nitric oxide. Antioxidant enzyme activities, as well as tissue ferric-reducing antioxidant power (FRAP) and malondialdehyde (MDA) levels, were evaluated. The expression of apoptotic genes and metastasis was measured using real-time polymerase chain reaction (PCR), while the expression of apoptotic proteins was evaluated using Western blotting. Finally, Ki-67 and p-53 were examined using immunohistochemistry to determine apoptosis. Results: The study found that BP, with its synergistic effects with DOX, reduced the volume of tumors and increased the expression of apoptotic genes and proteins. In a dose-dependent manner, groups receiving BP and DOX with their synergistic effects reduced the level of estrogen and nitric oxide and also reduced the level of pro-inflammatory cytokines. BP along with DOX increased serum interferon-γ (IFN-γ) levels. Tumor tissue FRAP and thiobarbituric acid reactive substances (TBARS) levels increased in BP-treated groups. Ki-67 and Bcl-2 proliferation markers levels decreased, and p53 levels increased in 4T1-breast tumors. Conclusion: The study concluded that BP with its synergistic effects along with DOX has the ability to suppress the growth of tumors and can also inhibit the oxidative damage of DOX. [ABSTRACT FROM AUTHOR]

Digital breast tomosynthesis (DBT) is a 3D breast cancer screening technique that can overcome the limitations of standard 2D digital mammography. However, DBT images often suffer from artifacts stemming from acquisition conditions, a limited angular range, and low radiation doses. These artifacts have the potential to degrade the performance of automated breast tumor classification tools. Notably, most existing automated breast tumor classification methods do not consider the effect of DBT image quality when designing the classification models. In contrast, this paper introduces a novel deep learning-based framework for classifying breast tumors in DBT images. This framework combines global image quality-aware features with tumor texture descriptors. The proposed approach employs a two-branch model: in the top branch, a deep convolutional neural network (CNN) model is trained to extract robust features from the region of interest that includes the tumor. In the bottom branch, a deep learning model named TomoQA is trained to extract global image quality-aware features from input DBT images. The quality-aware features and the tumor descriptors are then combined and fed into a fully-connected layer to classify breast tumors as benign or malignant. The unique advantage of this model is the combination of DBT image quality-aware features with tumor texture descriptors, which helps accurately classify breast tumors as benign or malignant. Experimental results on a publicly available DBT image dataset demonstrate that the proposed framework achieves superior breast tumor classification results, outperforming all existing deep learning-based methods. [ABSTRACT FROM AUTHOR]

Background: The aberrant amplification of mammary luminal progenitors is at the origin of basal-like breast cancers associated with BRCA1 mutations. Integrins mediate cell–matrix adhesion and transmit mechanical and chemical signals that drive epithelial stem cell functions and regulate tumor progression, metastatic reactivation, and resistance to targeted therapies. Consistently, we have recently shown that laminin-binding integrins are essential for the expansion and differentiation of mammary luminal progenitors in physiological conditions. As over-expression of the laminin-binding α6 integrin (Itgα6) is associated with poor prognosis and reduced survival in breast cancer, we here investigate the role of Itgα6 in mammary tumorigenesis. Methods: We used Blg-Cre; Brca1F/F; Trp53F/F mice, a model that phenocopies human basal-like breast cancer with BRCA1 mutations. We generated mutant mice proficient or deficient in Itgα6 expression and followed tumor formation. Mammary tumors and pretumoral tissues were characterized by immunohistochemistry, flow cytometry, RT-qPCR, Western blotting and organoid cultures. Clonogenicity of luminal progenitors from preneoplastic glands was studied in 3D Matrigel cultures. Results: We show that Itga6 deletion favors activation of p16 cell cycle inhibitor in the preneoplastic tissue. Subsequently, the amplification of luminal progenitors, the cell of origin of Brca1-deficient tumors, is restrained in Itgα6-deficient gland. In addition, the partial EMT program operating in Brca1/p53-deficient epithelium is attenuated in the absence of Itgα6. As a consequence of these events, mammary tumor formation is delayed in Itgα6-deficient mice. After tumor formation, the lack of Itgα6 does not affect tumor growth but rather alters their differentiation, resulting in reduced expression of basal cell markers. Conclusions: Our data indicate that Itgα6 has a pro-tumorigenic role in Blg-Cre; Brca1F/F; Trp53F/F mice developing basal-like mammary tumors. In particular, we reveal that Itgα6 is required for the luminal progenitor expansion and the aberrant partial EMT program that precedes the formation of BRCA1 deficient tumors. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to evaluate the prognostic role of p53 immunohistochemical (IHC) expression in a large cohort of patients with hormone receptors (HR)-positive/Her2-negative primary invasive breast cancer. Methods Retrospective review of consecutive cases treated at our Breast Unit between 2003 and 2013. Patients were divided into 3 subgroups based on p53 IHC expression: null (0%), low (0.1%-49%), and high (≥50%) p53 expression. Results A total of 1387 patients were included in the study with a median follow-up of 86 months. After adjusting for age, size, node status, lymphovascular invasion, progesterone, and Ki67 expression, only null p53 immunophenotype was associated with worse disease-free survival (DFS) (OR 1.74, 95% IC, 1.11-2.71, P  = .015) and distant recurrence-free survival (DRFS) (OR 1.73, 95% IC, 1.04-2.90, P  = .036). Null p53 impacted significantly DFS and DRFS also in patients with early breast cancer. Conclusions p53 IHC expression affects survival and, thus can be a valuable tool in the management of patients with HR-positive/Her2-negative breast cancer [ABSTRACT FROM AUTHOR]

Recent evidence has pointed out that the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) expression is a poor prognosis factor. However, the implications of CTLA-4 expression on circulating inflammatory mediators are unclear for breast cancer. Tumor biopsies and blood samples were collected from 117 breast cancer patients. Oxidative stress parameters were evaluated in plasma samples by measuring the lipoperoxidation profile and nitric oxide metabolites (NOx). Interleukins 12 (IL-12) and 4 (IL-4) were assessed by ELISA. CTLA-4 expression was determined by immunofluorescence assessed by its labeling in tumor-infiltrating leukocytes (TILs) or breast tumors. Correlations between CTLA-4 expression in breast tumors with TCD4/TCD8 infiltrating lymphocyte and inflammation-related genes were performed using data from TIMER 2.0/TCGA databases (n = 2160). CTLA-4 expression in TILs significantly correlated to triple-negative breast tumors. Patients carrying CTLA-4-positive tumors exhibited lower plasmatic NOx levels, and those expressing CTLA-4 in TILs had reduced levels of IL-12 in plasma. No changes in either IL-4 or lipid peroxidation profiles were detected concerning any CTLA4 status. Compared to the Luminal A ones, oxidative stress parameters and cytokines were observed in patients bearing triple-negative tumors. CTLA-4 expression in all breast cancer subtypes positively correlated to TCD4/TCD8 lymphocyte infiltrates, as well as to the pro-inflammatory genes IL12A, IL4, NFKB1, NFKB2, NOS1, NOS2, and NOS3. CTLA-4 expression in both tumor and TILs can affect the systemic inflammatory status of breast cancer patients, especially antitumor molecules such as IL-12 and NOx that correlate to more aggressive disease. [ABSTRACT FROM AUTHOR]

Introduction. There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods. We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results. Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion. Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses. [ABSTRACT FROM AUTHOR]

Digital breast tomosynthesis (DBT) stands out as a highly robust screening technique capable of enhancing the rate at which breast cancer is detected. It also addresses certain limitations that are inherent to mammography. Nonetheless, the process of manually examining numerous DBT slices per case is notably time-intensive. To address this, computer-aided detection (CAD) systems based on deep learning have emerged, aiming to automatically identify breast tumors within DBT images. However, the current CAD systems are hindered by a variety of challenges. These challenges encompass the diversity observed in breast density, as well as the varied shapes, sizes, and locations of breast lesions. To counteract these limitations, we propose a novel method for detecting breast tumors within DBT images. This method relies on a potent dynamic ensemble technique, along with robust individual breast tumor detectors (IBTDs). The proposed dynamic ensemble technique utilizes a deep neural network to select the optimal IBTD for detecting breast tumors, based on the characteristics of the input DBT image. The developed individual breast tumor detectors hinge on resilient deep-learning architectures and inventive data augmentation methods. This study introduces two data augmentation strategies, namely channel replication and channel concatenation. These data augmentation methods are employed to surmount the scarcity of available data and to replicate diverse scenarios encompassing variations in breast density, as well as the shapes, sizes, and locations of breast lesions. This enhances the detection capabilities of each IBTD. The effectiveness of the proposed method is evaluated against two state-of-the-art ensemble techniques, namely non-maximum suppression (NMS) and weighted boxes fusion (WBF), finding that the proposed ensemble method achieves the best results with an F1-score of 84.96% when tested on a publicly accessible DBT dataset. When evaluated across different modalities such as breast mammography, the proposed method consistently attains superior tumor detection outcomes. [ABSTRACT FROM AUTHOR]

Breast cancer is a genetically and clinically heterogeneous disease. Cancerous cells multiplying abnormally in the breast, eventually spreading to the rest of the body if untreated. Breast cancer almost exclusively occurs in women. Cancer is a major public health problem worldwide with millions of new cancer patients diagnosed each year and many deaths resulting from this disease. Worldwide, female breast cancer has now surpassed lung cancer as the most commonly diagnosed cancer. SUBJECTS: Ninety two females were included in the current study, they were classified into three groups, depending on their health status (patients and healthy women) and the type of tumor suffered by the study patients: 32 female patients with cancerous breast tumors before receiving chemotherapy, 30 female patients with benign breast tumors (the pathological control group) and 30 females, who were included as a healthy control group. METHODS: Sandwich-ELISA method was applied to evaluate adiponectin and interleukin-18 concentrations in the sera of the study participants. RESULTS: Assessment of the adiponectin revealed a significant increase in the samples of malignant breast tumors group when compared with those of benign breast tumors (p=0.000) and healthy individuals (p=0.002). Interleukin-18 levels in the malignancy tumor group were significantly lower than their levels in the pathological (p=0.007) as well as healthy (p=0.000) controls groups. This study shows apparent slight decrease of adiponectin concentrations in cancerous patients group after getting approximately three consecutive doses of chemotherapy in comparison with its levels pretreatment, while non-significant difference was noted when comparing interleukin-18 levels after receiving the last dose of chemotherapy with its level before starting treatment. Although the levels of interleukin-18 increased after the end of the recommended course of chemotherapy, it did not rise to the levels of this protein in the healthy control group. The individual efficiency (sensitivity) of the evaluated criteria in the current study for distinguishing between cancerous and benign breast tumors was convergent. While the study recorded the highest specificity (93%) for adiponectin while the lowest specificity (40%) was recorded in interleukin-18. Adiponectin and interleukin-18 were able to distinguish 28 out of 32 breast cancer samples (88%). [ABSTRACT FROM AUTHOR]

Breast cancer is the most common cancer in women. Breast masses are one of the distinctive signs for diagnosing breast cancer, and ultrasound is widely used for screening as a non-invasive and effective method for breast examination. In this study, we used the Mendeley and BUSI datasets, comprising 250 images (100 benign, 150 malignant) and 780 images (133 normal, 487 benign, 210 malignant), respectively. The datasets were split into 80% for training and 20% for validation. The accurate measurement and characterization of different breast tumors play a crucial role in guiding clinical decision-making. The area and shape of the different breast tumors detected are critical for clinicians to make accurate diagnostic decisions. In this study, a deep learning method for mass segmentation in breast ultrasound images is proposed, which uses densely connected U-net with attention gates (AGs) as well as channel attention modules and scale attention modules for accurate breast tumor segmentation.The densely connected network is employed in the encoding stage to enhance the network's feature extraction capabilities. Three attention modules are integrated in the decoding stage to better capture the most relevant features. After validation on the Mendeley and BUSI datasets, the experimental results demonstrate that our method achieves a Dice Similarity Coefficient (DSC) of 0.8764 and 0.8313, respectively, outperforming other deep learning approaches. The source code is located at github.com/zhanghaoCV/plos-one. [ABSTRACT FROM AUTHOR]

Background: Vasculogenic mimicry (VM) is an alternative intratumoral microcirculation system that depends on the capacity of tumor cells to reorganize and grow in three-dimensional (3D) channel architectures like the capillaries formed by endothelial cells. Both VM and angiogenesis may coordinately function to feed cancer cells, allowing tumor growth. Long noncoding RNAs (lncRNAs) regulate critical cellular functions in cancer cells, including cell proliferation, apoptosis, angiogenesis, invasion, and metastasis. The lncRNA, known as actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), has been described as an oncogene in diverse types of cancers. However, its role in VM and metastasis in triple-negative breast cancer (TNBC) is unknown. Methods: Reverse transcription and quantitative polymerase chain reaction (RT‒qPCR) experiments were performed to evaluate the expression of 10 selected lncRNAs from literature in metastatic and nonmetastatic biopsies from TNBC patients. The expression of AFAP1-AS1 was analyzed in Genotype-Tissue Expression Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) datasets. The AFAP1-AS1 expression was knocked in TNBC Hs578T cells by transfection of specific siRNAs. Channel-like formation assays were performed using 3D cultures over Matrigel in hypoxia-treated Hs578T cancer cells with diminished expression of AFAP1-AS1. The angiogenesis tests were conducted using human umbilical vein endothelial cells (HUVECs) and AFAP1-AS1- silenced Hs578T cells on 3D cell cultures. The presence of VM (CD31-/PAS+) in tumor tissues from TNBC patients with and without metastasis was assessed through immunohistochemistry using endothelial marker CD31 antibodies and periodic acid-Schiff (PAS) staining. Results: Compared with normal mammary tissues, AFAP1-AS1 expression was higher in breast cancer tissues. Moreover, AFAP1-AS1 expression was upregulated in the TNBC subtype compared to receptor-positive breast tumors. In addition, the expression of AFAP1-AS1 was correlated with the expression of the thirteen genes characteristic of a previously reported hypoxia signature. Interestingly, AFAP1-AS1 was upregulated in primary TNBC tumors from patients who developed metastasis compared with the nonmetastatic group. Functional analysis revealed that the knockdown of AFAP1-AS1 in Hs578T cells significantly impaired the hypoxia-induced VM, accompanied by a decrease in the development of 3D channel networks. Similarly, AFAP1-AS1 knockdown counteracts the angiogenic potential of cancer cells, as indicated by a reduction in the number of polygons, sprouting cells, and nodes in HUVEC cells. Remarkably, an increase in CD31-/PAS + staining of 3D channel networks in primary breast tumors from metastatic patients was found compared with the nonmetastatic group. Finally, we found that the number of blood vessels increased in the nonmetastatic group more than in the metastatic cohort. Conclusions: Our data suggested that AFAP1-AS1 controls both VM and angiogenesis in Hs578T breast cancer cells and that increased metastasis is associated with VM in TNBC patients. [ABSTRACT FROM AUTHOR]

Intraoperative surgical margin assessment remains a challenge during breast-conserving surgery. Here, we report a combined strategy of immuno–positron emission tomography (PET) for preoperative detection of breast cancer and guided assessment of margins in breast-conserving surgery through second near-infrared (NIR-II) fluorescence imaging of trophoblastic cell surface antigen 2 (TROP2). We demonstrated that the intensity of PET signals in the tumors was nearly five times higher than in normal breast tissue with a zirconium-89 tracer conjugated to sacituzumab govitecan (SG) in a mouse spontaneous breast cancer model, enabling the identification of tumors. We further generated a NIR-II probe of indocyanine green conjugated to SG (ICG-SG) and developed a rapid incubation imaging method for intraoperative margin assessment in a relevant time window for the operation workflow. The ICG-SG NIR-II fluorescence image guidance was first verified to remove tumors completely and accurately in mouse breast cancer models. Moreover, the rapid incubation imaging method was applied to distinguish benign and malignant breast lesions in samples from 26 patients with breast cancer. Therefore, we have developed both nuclide and optical probes targeting TROP2 for rapid and precise identification of tumor margins during breast-conserving surgery in humans. Editor's summary: Identification of tumor borders is essential for effective surgical management of breast cancer. TROP2 is expressed in breast tumors but not normal mammary tissues. Here, Chen et al. developed imaging probes with the TROP2-targeted sacituzumab govitecan (SG) antibody-drug conjugate to assist surgeons in determining tumor versus normal mammary tissues before and during surgery. Labeling of SG with the near-infrared (NIR) fluorophore indocyanine green (ICG) supported the identification of TROP2+ tumor margins in NIR-II–guided surgery in murine breast tumor models. A rapid ex vivo tissue staining method with SG-ICG was also developed to intraoperatively evaluate TROP2+ tumor margins during human breast-conserving surgery. TROP2 probes are a promising approach for improving surgical removal of breast tumors. —Molly Ogle [ABSTRACT FROM AUTHOR]

Introduction: Breast asymmetry (BA) is a common condition in patients with adolescent idiopathic scoliosis (AIS). Physicians may misdiagnose a patient with a unilateral breast tumor as a normal condition related to scoliosis. The present report describes the case of a patient with a breast tumor that was detected incidentally after surgical correction of scoliosis. Patient Presentation and Outcomes: A 21-year-old woman was diagnosed as having AIS and reported to our institute for management. Thoracic third to lumbar second vertebra instrumented spine de-rotation and associated fusion surgery were performed to correct the deformity. After the operation, enlargement of left breast volume and obvious BA were noted. Breast sonography was performed, and a large tumor was found. Finally, the biopsy revealed a fibroadenoma of the left breast. Conclusions: In managing patients with scoliosis and BA, comprehensive consideration of other possible etiologies is crucial to prevent misdiagnosis. This article reminds physicians that breast tumors can be concealed by BA related to AIS. [ABSTRACT FROM AUTHOR]

Background/Objectives: Heterodimer peptides targeting more than one receptor can be advantageous, as tumors can simultaneously express more than one receptor type. For human breast cancer, a promising biological target is tumor angiogenesis through αvβ3 integrin expression. Another promising target is Neuropeptide Y receptors, considering Y1R is overexpressed in 90% of human breast tumors. This article details the development and preclinical evaluation, both in vitro and in vivo, of a novel heterodimer peptide dual-receptor-targeting probe, [99mTc]HYNIC-cRGDfk-NPY, designed for imaging breast tumors. Methods: Female BALB/c healthy mice were used to perform biodistrubution studies and female SCID mice were subcutaneously injected with MCF-7 and MDA-MB-231 tumor cells. [99mTc]HYNIC-cRGDfk-NPY was intravenously administered to the mice, followed by ex vivo biodistribution studies and small-animal SPECT/CT imaging. Nonspecific tracer uptake in both models was determined by coinjecting an excess of unlabeled HYNIC-cRGDfk-NPY (100 µg) along with the radiolabeled tracer. Results: Imaging and biodistribution data demonstrate good uptake to estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) tumor models. The in vivo tumor uptakes of radiolabeled conjugate were 9.30 ± 3.25% and 4.93 ± 1.01% for MCF-7 and MDA-MB231, respectively. The tumor/muscle ratios were 5.65 ± 0.94 for the MCF-7 model and 7.78 ± 3.20 for MDA-MB231. Conclusions: [99mTc]HYNIC-cRGDfk-NPY demonstrated rapid blood clearance, renal excretion, and in vivo tumor uptake, highlighting its potential as a tumor imaging agent. [ABSTRACT FROM AUTHOR]

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of BMC Medical Informatics & Decision Making is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The hypermethylation status of the promoter region of the breast cancer 1 (BRCA1), a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of BRCA1 promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that BRCA1 promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the BRCA1 promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs. [ABSTRACT FROM AUTHOR]

BRCA1 variants are extensively associated with increased risk of breast cancer. Early detection and screening of variants is still rare in developing countries. Here, we investigated six BRCA1 variants in 300 subjects from Pakistani population using tetra amplification‐refractory mutation system (T‐ARMS) PCR. Our results indicate significant association of BRCA1 variants rs8176237 (AA; OR 8.2, 95% CI 3.02–22.64, p < 0.0001), rs1060915 (CC; OR 4.29, 95% CI 1.94–9.48, p = 0.0003), and rs799912 (TT; OR 3.16, 95% CI 1.44–6.94, p = 0.004) with up to 8‐fold increased odds of breast cancer under recessive model. Furthermore, BRCA1 haplotypes AGCACG and AGCCCT were associated with up to 18% breast cancer cases (p < 0.05). Additionally, we found association of these variants with up to 11‐fold increased odds of benign breast tumors. Linkage disequilibrium (LD) block‐wise analysis revealed haplotypes GCAC and ATAC were associated with significantly increased risk. To our knowledge, this is the first study that identifies the association of these BRCA1 variants with breast tumors in Pakistani population. In conclusion, BRCA1 variants investigated in the present study are associated with high odds of benign‐ and malignant breast tumors. Studies with bigger sample size may help early detection and screening to reduce the odds of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer, as is commonly assumed, one of the most diagnosed kind of cancer is a multifactorial disease, its exact cause is still unknown. It is considered the second killer cancer among women. The present study participants were Iraqi women patients in pre-malignant and malignant (n=59) women with breast tumors as well as age matched healthy Iraqi women (n=27). This study aimed to evaluate the redox status upon transformation from premalignant (benign) to malignant stage of breast cancer by evaluating the saliva-blood correlation to look for the possibility using saliva as alternative fluid for diagnosis of the tumor stages. This was achieved by measuring the [total oxidant status level (TOS), total antioxidant status level (TAS), and oxidative stress index level(OSI). (TOS) and (TAS) were determined in saliva and serum fluid samples from all participants using colorimetric methods, while the oxidative stress index (OSI) was calculated. The results obtained from the study showed that the P value ≤ 0.01 significantly increased the measured [TOS] level and the calculated [OSI] level in saliva and serum fluid samples in contrast significantly decreased the P value ≤ 0.01 in the [TAS] level in both types of fluids of the patient groups compared to that of the healthy control group. Similar results were obtained when the values of these parameters were compared in both samples (serum and saliva) samples were compared between the patient groups in both breast tumors (Premalignant& malignant). [ABSTRACT FROM AUTHOR]

Background: Breast cancer treatment response evaluation using the response evaluation criteria in solid tumors (RECIST) guidelines, based on tumor volume changes, has limitations, prompting interest in novel imaging markers for accurate therapeutic effect determination. Purpose: To use MRI‐measured cell size as a new imaging biomarker for assessing chemotherapy response in breast cancer. Study Type: Longitudinal; animal model. Study Population: Triple‐negative human breast cancer cell (MDA‐MB‐231) pellets (4 groups, n = 7) treated with dimethyl sulfoxide (DMSO) or 10 nM of paclitaxel for 24, 48, and 96 hours, and 29 mice with MDA‐MB‐231 tumors in right hind limbs treated with paclitaxel (n = 16) or DMSO (n = 13) twice weekly for 3 weeks. Field Strength/Sequence: Oscillating gradient spin echo and pulsed gradient spin echo sequences at 4.7 T. Assessment: MDA‐MB‐231 cells were analyzed using flowcytometry and light microscopy to assess cell cycle phases and cell size distribution. MDA‐MB‐231 cell pellets were MR imaged. Mice were imaged weekly, with 9, 6, and 14 being sacrificed for histology after MRI at weeks 1, 2, and 3, respectively. Microstructural parameters of tumors/cell pellets were derived by fitting diffusion MRI data to a biophysical model. Statistical Tests: One‐way ANOVA compared cell sizes and MR‐derived parameters between treated and control samples. Repeated measures 2‐way ANOVA with Bonferroni post‐tests compared temporal changes in MR‐derived parameters. A P‐value <0.05 was considered statistically significant. Results: In vitro experiments showed that the mean MR‐derived cell sizes of paclitaxel‐treated cells increased significantly with a 24‐hours treatment and decreased (P = 0.06) with a 96‐hour treatment. For in vivo xenograft experiments, the paclitaxel‐treated tumors showed significant decreases in cell size at later weeks. MRI observations were supported by flowcytometry, light microscopy, and histology. Data Conclusions: MR‐derived cell size may characterize the cell shrinkage during treatment‐induced apoptosis, and may potentially provide new insights into the assessment of therapeutic response. Level of Evidence: 2 Technical Efficacy Stage: 4. [ABSTRACT FROM AUTHOR]

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight. [ABSTRACT FROM AUTHOR]

Background: Prevention and treatment of metastatic breast cancer (BC) is an unmet clinical need. The retinoic acid derivative fenretinide (FeR) was previously evaluated in Phase I-III clinical trials but, despite its excellent tolerability and antitumor activity in preclinical models, showed limited therapeutic efficacy due to poor bioavailability. We recently generated a new micellar formulation of FeR, Bionanofenretinide (Bio-nFeR) showing enhanced bioavailability, low toxicity, and strong antitumor efficacy on human lung cancer, colorectal cancer, and melanoma xenografts. In the present study, we tested the effect of Bio-nFeR on a preclinical model of metastatic BC. Methods: We used BC cell lines for in vitro analyses of cell viability, cell cycle and migratory capacity. For in vivo studies, we used HER2/neu transgenic mice (neuT) as a model of spontaneously metastatic BC. Mice were treated orally with Bio-nFeR and at sacrifice primary and metastatic breast tumors were analyzed by histology and immunohistochemistry. Molecular pathways activated in primary tumors were analyzed by immunoblotting. Stem cell content was assessed by flow cytometry, immunoblotting and functional assays such as colony formation ex vivo and second transplantation assay in immunocompromised mice. Results: Bio-nFeR inhibited the proliferation and migration of neuT BC cells in vitro and showed significant efficacy against BC onset in neuT mice. Importantly, Bio-nFeR showed the highest effectiveness against metastatic progression, counteracting both metastasis initiation and expansion. The main mechanism of Bio-nFeR action consists of promoting tumor dormancy through a combined induction of antiproliferative signals and inhibition of the mTOR pathway. Conclusion: The high effectiveness of Bio-nFeR in the neuT model of mammary carcinogenesis, coupled with its low toxicity, indicates this formulation as a potential candidate for the treatment of metastatic BC and for the adjuvant therapy of BC patients at high risk of developing metastasis. [ABSTRACT FROM AUTHOR]

Background TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. Methods Breast (N  = 11 246), colorectal (N  = 15 425), hepatocellular (N  = 433), pancreatic (N  = 5488), and urothelial (N  = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Results Several pathogenic mutations were associated with TACSTD2 -high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2 -high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2 -low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS -mutant tumors. Patients with breast cancer with TACSTD2 -high tumors also experienced significantly worse OS following immune checkpoint inhibitors. Conclusions TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors. [ABSTRACT FROM AUTHOR]

Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin's multiaxial role in breast cancer progression and recurrence. Osteopontin promotes tumor growth in several cancer types. Here, in a preclinical model recapitulating features of human breast cancer recurrence, the authors report that osteopontin promotes the recruitment of immunosuppressive macrophages and its targeting reduces breast tumor growth and metastasis. [ABSTRACT FROM AUTHOR]

Open nanoshells such as nanobowls or nanocups collectively described as 'semi shells' have unique plasmonic properties due to their lack of symmetry. So far, their fabrication was based on multistep and laborious methods such as solid state sputter coating or selective deposition/etching using sacrificial templates. In this work, we report a rapid one step colloidal synthetic protocol for PEGylated semi-shell (SS) fabrication by simultaneous facet specific anisotropic chemical etching of rhombic dodecahedral ZIF-8 and heterogenous nucleation & growth of gold. The SS possesses a strong localized surface plasmon resonance in the near-infrared region, which is retained after surface passivation with polyethylene glycol and subsequent cryopreservation for extended shelf-life. Freshly reconstituted PEGylated SS was found to be safe & non-toxic in healthy C57BL/6 mice post intravenous administration. The PEGylated SS displayed significant photothermal efficiency of ~37% with 808 nm laser irradiation. Preclinical assessment of intra-tumoral photothermal efficacy indicated complete remission of primary breast tumor mass with insignificant metastasis to vital organs in 4T1 FL2 tumor bearing CD1 nude mice. Further, PEGylated SS mediated photothermal therapy also yielded morbidity free survivael of 75% for up to 90 days, indicating their potential to significantly improve outcomes in advanced breast tumors. Anisotropic gold-based colloidal nanoparticles such as semi shells have unique optical properties and widespread applications such as in bioimaging, biosensing and therapy, however, the fabrication process of semi shells remains a challenge due to laborious multistep solid state and colloidal procedures. In this study, the authors develop a rapid one-pot colloidal synthetic route for the fabrication of semi shells using ZIF-8 as a sacrificial template, and demonstrate their promise for photothermal therapy. [ABSTRACT FROM AUTHOR]

This document is a commentary on an article titled "AI-based time-intensity-curve assessment of breast tumors on MRI" published in the journal European Radiology. The article discusses the use of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess breast tumors. It explains that the qualitative and quantitative assessment of DCE-MRI data is based on evaluations of time-intensity curve (TIC) shapes, which can help differentiate between benign and malignant lesions. The commentary highlights a new approach that quantifies contrast enhancement over multiple phases of DCE-MRI and classifies the TIC into 19 different subtypes, achieving promising results for the differentiation of benign and malignant breast lesions. The authors suggest that this approach could provide additional quantitative information to enhance the diagnostic performance of DCE-MRI in a clinical setting. [Extracted from the article]

Simple Summary: Breast cancer remains a major health issue in the United States and around the world. While progress has been made in curing most types of breast cancer, there are currently no effective cures for a subtype called 'triple-negative' breast cancer. We have identified a gene named BORG that, based on experiments in cultured human cells and mice, plays an important role in triple-negative breast cancer. Here, we study the function of this gene in a large group of human triple-negative breast cancers and show that when the level of expression of this gene is high, tumors become more invasive and develop 'triple-negative'-like properties. Even in non-triple-negative tumors, high levels of expression of this gene are associated with more aggressive tumor behavior and poor response to therapy. Based on these validation studies in human tumors, we hope to leverage mechanistic vulnerabilities in BORG action to one day advance novel therapeutic strategies to alleviate hard-to-cure triple-negative breast tumors. Background/Objectives: Long noncoding RNAs (lncRNAs) are known to play key roles in breast cancers; however, detailed mechanistic studies of lncRNA function have not been conducted in large cohorts of breast cancer tumors, nor has inter-donor and inter-subtype variability been taken into consideration for these analyses. Here we provide the first identification and annotation of the human BORG lncRNA gene. Methods/Results: Using multiple tumor cohorts of human breast cancers, we show that while BORG expression is strongly induced in breast tumors as compared to normal breast tissues, the extent of BORG induction varies widely between breast cancer subtypes and even between different tumors within the same subtype. Elevated levels of BORG in breast tumors are associated with the acquisition of core cancer aggression pathways, including those associated with basal tumor and pluripotency phenotypes and with epithelial–mesenchymal transition (EMT) programs. While a subset of BORG-associated pathways was present in high BORG-expressing tumors across all breast cancer subtypes, many were specific to tumors categorized as triple-negative breast cancers. Finally, we show that genes induced by heterologous expression of BORG in murine models of TNBC both in vitro and in vivo strongly overlap with those associated with high BORG expression levels in human TNBC tumors. Conclusion: Our findings implicate human BORG as a novel driver of the highly aggressive basal TNBC tumor phenotype. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

High-risk benign breast tumors are known to develop breast cancer at high rates. However, it is still controversial whether they should be removed during diagnosis or followed up until cancer development becomes evident. Therefore, this study sought to identify circulating microRNAs (miRNAs) that could serve as detection markers of cancers arising from high-risk benign tumors. Small RNA-seq was performed using plasma samples collected from patients with early-stage breast cancer (CA) and high-risk (HB), moderate-risk (MB), and no-risk (Be) benign breast tumors. Proteomic profiling of CA and HB plasma was performed to investigate the underlying functions of the identified miRNAs. Our findings revealed that four miRNAs, hsa-mir-128-3p, hsa-mir-421, hsa-mir-130b-5p, and hsa-mir-28-5p, were differentially expressed in CA vs. HB and had diagnostic power to discriminate CA from HB with AUC scores greater than 0.7. Enriched pathways based on the target genes of these miRNAs indicated their association with IGF-1. Furthermore, the Ingenuity Pathway Analysis performed on the proteomic data revealed that the IGF-1 signaling pathway was significantly enriched in CA vs. HB. In conclusion, these findings suggest that these miRNAs could potentially serve as biomarkers for detecting early-stage breast cancer from high-risk benign tumors by monitoring IGF signaling-induced malignant transformation. [ABSTRACT FROM AUTHOR]

We have developed an imaging biomarker for quantitatively monitoring the response to clinical treatment in cancer patients. Similar to other diffusion-weighted imaging DWI techniques, our method allows for the monitoring of breast cancer progression based on the diffusion coefficient values in the affected area. Our technique has the advantage of using images from mammograms and mesoscopic multiparticle collision MPC simulation, making it more affordable and easier to implement compared to other DWI techniques, such as diffusion-weighted MRI. To create our simulation, we start with the region of interest from a mammogram where the lesion is located and build a flat simulation box with impenetrable cylindrical obstacles of varying diameters to represent the tissue's heterogeneity. The volume of each obstacle is based on the intensity of the mammogram pixels, and the diffusion coefficient is calculated by simulating the behavior of a point particle fluid inside the box using MPC. We tested our technique on two mammograms of a male patient with a moderately differentiated breast ductal carcinoma lesion, taken before and after the first cycle of four chemotherapy sessions. As seen in other DWI studies, our technique demonstrated significant changes in the fluid concentration map of the tumor lesion, and the relative values of the diffusion coefficient showed a clear difference before and after chemotherapy. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype, with a poor survival rate compared to others subtypes. For a long time, chemotherapy was the only systemic treatment for TNBC, and the identification of actionable molecular targets might ultimately improve the prognosis for TNBC patients. We performed a genome-wide analysis of DNA methylation at CpG islands on a collection of one hundred ten breast carcinoma samples and six normal breast tissue samples using reduced representation bisulfite sequencing with the XmaI restriction enzyme (XmaI-RRBS) and identified a subset of TNBC samples with significant hypomethylation at the LTB4R/LTB4R2 genes' CpG islands, including CpG dinucleotides covered with cg12853742 and cg21886367 HumanMethylation 450K microarray probes. Abnormal DNA hypomethylation of this region in TNBC compared to normal samples was confirmed by bisulfite Sanger sequencing. Gene expression generally anticorrelates with promoter methylation, and thus, the promoter hypomethylation detected and confirmed in our study might be revealed as an indirect marker of high LTB4R/LTB4R2 expression using a simple methylation-sensitive PCR test. Analysis of RNA-seq expression and DNA methylation data from the TCGA dataset demonstrates that the expression of the LTB4R and LTB4R2 genes significantly negatively correlates with DNA methylation at both CpG sites cg12853742 (R = −0.4, p = 2.6 × 10−6; R = −0.21, p = 0.015) and cg21886367 (R = −0.45, p = 7.3 × 10−8; R = −0.24, p = 0.005), suggesting the upregulation of these genes in tumors with abnormal hypomethylation of their CpG island. Kaplan–Meier analysis using the TCGA-BRCA gene expression and clinical data revealed poorer overall survival for TNBC patients with an upregulated LTB4R. To this day, only the leukotriene inhibitor LY255283 has been tested on an MCF-7/DOX cell line, which is a luminal A breast cancer molecular subtype. Other studies compare the effects of Montelukast and Zafirlukast (inhibitors of the cysteinyl leukotriene receptor, which is different from LTB4R/LTB4R2) on the MDA-MB-231 (TNBC) cell line, with high methylation and low expression levels of LTB4R. In our study, we assess the therapeutic effects of various drugs (including leukotriene receptor inhibitors) with the DepMap gene effect and drug sensitivity data for TNBC cell lines with hypomethylated and upregulated LTB4R/LTB4R2 genes. LY255283, Minocycline, Silibinin, Piceatannol, Mitiglinide, 1-Azakenpaullone, Carbetocin, and Pim-1-inhibitor-2 can be considered as candidates for the additional treatment of TNBC patients with tumors demonstrating LTB4R/LTB4R2 hypomethylation/upregulation. Finally, our results suggest that the epigenetic status of leukotriene B4 receptors is a novel, potential, predictive, and prognostic biomarker for TNBC. These findings might improve individualized therapy for TNBC patients by introducing new therapeutic adjuncts as anticancer agents. [ABSTRACT FROM AUTHOR]

Background: Social behaviors such as altruism, where one self-sacrifices for collective benefits, critically influence an organism's survival and responses to the environment. Such behaviors are widely exemplified in nature but have been underexplored in cancer cells which are conventionally seen as selfish competitive players. This multidisciplinary study explores altruism and its mechanism in breast cancer cells and its contribution to chemoresistance. Methods: MicroRNA profiling was performed on circulating tumor cells collected from the blood of treated breast cancer patients. Cancer cell lines ectopically expressing candidate miRNA were used in co-culture experiments and treated with docetaxel. Ecological parameters like relative survival and relative fitness were assessed using flow cytometry. Functional studies and characterization performed in vitro and in vivo include proliferation, iTRAQ-mass spectrometry, RNA sequencing, inhibition by small molecules and antibodies, siRNA knockdown, CRISPR/dCas9 inhibition and fluorescence imaging of promoter reporter-expressing cells. Mathematical modeling based on evolutionary game theory was performed to simulate spatial organization of cancer cells. Results: Opposing cancer processes underlie altruism: an oncogenic process involving secretion of IGFBP2 and CCL28 by the altruists to induce survival benefits in neighboring cells under taxane exposure, and a self-sacrificial tumor suppressive process impeding proliferation of altruists via cell cycle arrest. Both processes are regulated concurrently in the altruists by miR-125b, via differential NF-κB signaling specifically through IKKβ. Altruistic cells persist in the tumor despite their self-sacrifice, as they can regenerate epigenetically from non-altruists via a KLF2/PCAF-mediated mechanism. The altruists maintain a sparse spatial organization by inhibiting surrounding cells from adopting the altruistic fate via a lateral inhibition mechanism involving a GAB1-PI3K-AKT-miR-125b signaling circuit. Conclusions: Our data reveal molecular mechanisms underlying manifestation, persistence and spatial spread of cancer cell altruism. A minor population behave altruistically at a cost to itself producing a collective benefit for the tumor, suggesting tumors to be dynamic social systems governed by the same rules of cooperation in social organisms. Understanding cancer cell altruism may lead to more holistic models of tumor evolution and drug response, as well as therapeutic paradigms that account for social interactions. Cancer cells constitute tractable experimental models for fields beyond oncology, like evolutionary ecology and game theory. [ABSTRACT FROM AUTHOR]

Background: Compared to conventional 2D mammography, digital breast tomosynthesis (DBT) offers greater breast lesion detection rates. Ring-like hypodense artifacts surrounding dense lesions are a common byproduct of DBT. This study's purpose was to assess whether minuscule changes spanning this halo—termed the "broken halo sign"—could improve lesion classification. Methods: This retrospective study was approved by the local ethics review board. After screening 288 consecutive patients, DBT studies of 191 female participants referred for routine mammography with a subsequent histologically verified finding of the breast were assessed. Examined variables included patient age, histological diagnosis, architectural distortion, maximum size, maximum halo depth, conspicuous margins, irregular shape and broken halo sign. Results: While a higher halo strength was indicative of malignancy in general (p = 0.031), the broken halo sign was strongly associated with malignancy (p < 0.0001, odds ratio (OR) 6.33), alongside architectural distortion (p = 0.012, OR 3.49) and a diffuse margin (p = 0.006, OR 5.49). This was especially true for denser breasts (ACR C/D), where the broken halo sign was the only factor predicting malignancy (p = 0.03, 5.22 OR). Conclusion: DBT-associated halo artifacts warrant thorough investigation in newly found breast lesions as they are associated with malignant tumors. The "broken halo sign"—the presence of small lines of variable diameter spanning the peritumoral areas of hypodensity—is a strong indicator of malignancy, especially in dense breasts, where architectural distortion may be obfuscated due to the surrounding tissue. [ABSTRACT FROM AUTHOR]

This article proposes a low‐profile ultra‐wideband (UWB) antenna for breast tumor detection using the monostatic radar‐based microwave imaging (RBMI) technique. The proposed UWB antenna consists of a circular patch and ground plane along with a modified tapered feed line having a total size of 13 × 9 × 1.6 mm3. The designed antenna operates from 4 to 11 GHz based on a −10 dB reflection coefficient with a peak gain of 9.5 dBi at 4.8 GHz. Experimental validation is carried out after fabricating the prototype of the UWB antenna and the breast mimic. The measured backscattered signals are captured using the vector network analyzer (E‐5063A) by keeping the antenna at 10 mm from the breast phantom. After that, post‐processing of the measured data is done to detect the exact depth and location of the malignant tissue. The proposed antenna uses UWB band frequency of operation because it has some unique features, that is, it provides immunity to multipath fading, has a simple design, has a low cost of fabrication, and has biological friendliness. Moreover, due to the proposed antenna's resonance at a lower resonant frequency better depth of penetration is achieved in human body phantoms and the proposed antenna provides specific absorption rates (SAR) of 0.877 W/kg over 1 g of tissue at 4.8 GHz, which is an acceptable limit for SAR as per FCC guidelines. Therefore, the proposed antenna and monostatic RBMI technique are good candidates for breast tumor detection. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is the most prevalent cancer and is second leading cause of death from malignancy among women worldwide. In addition to tumor factors, the host characteristics of tumors have been paid more and more attention by the medical community. This study aimed to develop a breast cancer prediction model for the Chinese population using clinical and biochemical characteristics. Methods: This is a retrospective study. From 2012 to 2021, we selected 19,751 patients with breast diseases from the Guangdong Hospital of Traditional Chinese Medicine, which included 5660 patients with breast cancer and 14,091 patients with benign breast diseases—75% of patients were randomly assigned to the training group and 25% to the test group using a total of 34 clinical and biochemical characteristics. Significant clinical signs were investigated, and logistic regression with recursive feature elimination (RFE) model was used to develop a prediction model for distinguishing benign from malignant breast diseases. The prediction model's accuracy, precision, sensitivity, specificity, and area under the ROC curve (AUC) were calculated. Results: Clinical statistics demonstrated that the prediction model comprised 19 clinical characteristics had statistical separability in both the training group and the test group, as well as good sensitivity and prediction. Conclusions: This model based on biochemical parameters demonstrates a significant predictive effect for breast cancer and may be useful as a reference for invasive tissue biopsy in patients undergoing BI-RADS 3 and 4A breast imaging. [ABSTRACT FROM AUTHOR]

The hypoxic tumor microenvironment (TME) significantly affects cancer treatment. Conventional chemotherapeutic agents cannot effectively target hypoxic tumor tissue, which decreases efficacy and results in severe toxic side effects. To alleviate this problem, a self‐driving biomotor is developed by functionalizing MCDP nanoparticles containing calcium peroxide and doxorubicin (DOX) loaded onto polydopamine‐coated metal–organic frameworks（MOF）, with the anaerobic Bifidobacterium infantis (Bif) for synergistic chemotherapy and chemodynamic therapy (CDT) against breast cancer. The materials of institute Lavoisier (MIL) frameworks + CaO2 + DOX + polydopamine (MCDP)@Bif biohybrid actively targets hypoxic regions of solid tumors via the inherent targeting ability of Bif. Once it has accumulated in the tumor tissue, MCDP generates hydroxyl radicals through the enhanced Fenton‐type reactions between Fe2+ and self‐generated hydrogen peroxide in the acidic TME. The disruption of Ca2+ homeostasis and resulting mitochondrial Ca2+ overload triggers apoptosis and enhances oxidative stress, promoting tumor cell death. The results found that the DOX concentration in MCDP@Bif‐treated tumors is 3.8 times higher than that in free‐DOX‐treated tumors, which significantly prolongs the median survival of the tumor‐bearing mice to 69 days and reduces the toxic side effects of DOX. Therefore, the novel bacteria‐driven drug delivery system is highly effective in achieving synergistic chemotherapy and CDT against solid tumors. [ABSTRACT FROM AUTHOR]

The TP53 tumor suppressor gene is mutated early in the majority of patients with triple-negative breast cancer (TNBC). The most frequent TP53 alterations are missense mutations that contribute to tumor aggressiveness. We developed an autochthonous somatic K14-Cre driven TNBC mouse model with p53R172H and p53R245W mutations in which mutant p53 can be toggled on and off genetically while leaving the tumor microenvironment intact and wild-type for p53. These mice develop TNBCs with a median latency of 1 y. Deletion of mutant p53R172H or p53R245W in vivo in these tumors blunts their tumor growth and significantly extends survival of mice. Downstream analyses revealed that deletion of mutant Trp53 activated the cyclic GMP-AMP Synthase-Stimulator of Interferon Genes pathway but did not cause apoptosis implicating other mechanisms of tumor regression. Furthermore, we determined that only tumors with stable mutant p53 are dependent on mutant p53 for growth. [ABSTRACT FROM AUTHOR]