Extreme Oncoplasty: Oncologically Safe When Compared with Mastectomy.

BACKGROUND: Extreme oncoplasty is a breast-conserving operation using oncoplastic techniques in a patient who does not meet the traditional criteria for breast conservation and in whom most physicians would suggest a mastectomy. These tumors are generally multicentric and/or multifocal, they span more than 50 mm, or they can be large recurrences in a previously irradiated breast. METHODS: A prospective single institution database was queried from 2008 through mid 2023 for patients who met the criteria for extreme oncoplasty and were treated with excision plus whole-breast radiation therapy (WBRT) or mastectomy without WBRT. Patients with recurrent breast cancer were excluded. Endpoints were local, regional, and distant recurrence as well as overall and breast-cancer-specific survival. RESULTS: 272 patients were treated with oncoplastic mammaplasty, using a standard or split reduction excision followed by postoperative WBRT. An additional 101 patients elected to be treated with mastectomy without postoperative radiation therapy. With a median follow-up of 7 years, there were no significant differences in local, regional, or distant recurrence, nor in breast-cancer-specific survival or overall survival. CONCLUSIONS: We strongly support extreme oncoplasty plus WBRT as the default procedure of choice for patients with large multifocal/multicentric lesions amenable to reconstruction with volume displacement mammaplasty.

Feasibility and acceptability of study methods and psychosocial interventions for body image among women diagnosed with breast cancer: A systematic review and narrative synthesis.

OBJECTIVE: This systematic review aimed to summarize evidence for the feasibility and acceptability of psychosocial interventions for body image among women diagnosed with breast cancer and the study methods used to evaluate the interventions in question. METHODS: Articles were identified via MEDLINE, CINAHL, CENTRAL, PsychINFO, and EMBASE. Inclusion criteria were: (1) peer-reviewed publication in English from 2000 onward with accessible full-text, (2) reported data on the feasibility and/or acceptability of psychosocial interventions and/or study methods, (3) included at least one measure of body image or reported a body-related theme, and (4) sample comprised women diagnosed with breast cancer. All study designs were eligible. Two reviewers independently performed study selection, data extraction, and quality assessment. RESULTS: Sixty-two articles were included. Participants and comparator groups varied as did interventions. Feasibility and acceptability of the interventions and study methods were inconsistently operationalized and reported across studies. Evidence of feasibility and acceptability was heterogeneous within and across studies, though mostly positive. CONCLUSION: Published psychosocial interventions for body image and study methods are generally feasible and acceptable. Findings should be used to advance the development, implementation, and evaluation of interventions designed to improve outcomes (body image or otherwise) for women diagnosed with breast cancer. SYSTEMATIC REVIEW REGISTRATION: This review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42021269062, 11 September 2021).

Identification of FTY720 and COH29 as novel topoisomerase I catalytic inhibitors by experimental and computational studies.

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes. Molecular docking revealed that FTY720 and COH29 interacted favorably with TOP1. Molecular dynamics simulations revealed that FTY720 and COH29 could affect the catalytic domain of TOP1, thus resulting in altered DNA-binding cavity size. The alanine scanning and interaction entropy identified Arg536 as a hotspot residue. In addition, the bioinformatics analysis predicted that FTY720 and COH29 could be effective in treating malignant breast tumors. Biological experiments verified their antitumor activities using MCF-7 breast cancer cells. Their combinatory effects with TOP1 poisons were also investigated. Further, FTY720 and COH29 were found to cause less DNA damage compared with TOP1 poisons. The findings provide reliable lead compounds for the development of novel TOP1 catalytic inhibitors and offer new insights into the potential clinical applications of FTY720 and COH29 in targeting TOP1.

The Size Differences of Breast Cancer and Benign Tumors Measured by Two-Dimensional Ultrasound and Contrast-Enhanced Ultrasound.

OBJECTIVES: Ultrasound (US) imaging has been observed to underestimate tumor size in clinical practice. This study aims to compare the size measurements of breast cancer and benign tumors using two-dimensional ultrasound (2DUS) and contrast-enhanced ultrasound (CEUS). METHODS: The study included 42 clinically confirmed breast cancer and 47 benign breast tumors. Two experienced physicians independently measured the maximal longitudinal and transverse diameters of the masses in 2DUS and CEUS. All analyses were performed in R (4.2.2) and GraphPad Prism 6. RESULTS: The maximal longitudinal and transverse diameters of breast cancer measured by CEUS were 26.61 ± 0.21% and 26.24 ± 0.19% larger compared with 2DUS, and benign breast tumors had an 11.74 ± 0.21% and 11.06 ± 0.14% increase in size compared with 2DUS. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) for the difference between 2DUS and CEUS was 0.870 for longitudinal diameters (95% CI: 0.795-0.945, sensitivity 0.842, specificity 0.783, threshold value 0.215), and 0.863 for transverse diameters (95% CI: 0.785-0.942, sensitivity 0.667, specificity 0.936, threshold value 0.203). CONCLUSIONS: The size measurements of both breast cancer and benign tumors were larger in CEUS compared with 2DUS, with CEUS measurements of breast cancer being more pronounced than those of benign breast tumors. These findings suggest that CEUS may provide a more precise assessment of tumor size, which is crucial for determining optimal treatment strategies and improving patient outcomes in breast cancer management.

Application of an artificial intelligence-based system in the diagnosis of breast ultrasound images obtained using a smartphone.

BACKGROUND: Breast ultrasound (US) is useful for dense breasts, and the introduction of artificial intelligence (AI)-assisted diagnoses of breast US images should be considered. However, the implementation of AI-based technologies in clinical practice is problematic because of the costs of introducing such approaches to hospital information systems (HISs) and the security risk of connecting HIS to the Internet to access AI services. To solve these problems, we developed a system that applies AI to the analysis of breast US images captured using a smartphone. METHODS: Training data were prepared using 115 images of benign lesions and 201 images of malignant lesions acquired at the Division of Breast Surgery, Gifu University Hospital. YOLOv3 (object detection models) was used to detect lesions on US images. A graphical user interface (GUI) was developed to predict an AI server. A smartphone application was also developed for capturing US images displayed on the HIS monitor with its camera and displaying the prediction results received from the AI server. The sensitivity and specificity of the prediction performed on the AI server and via the smartphone were calculated using 60 images spared from the training. RESULTS: The established AI showed 100% sensitivity and 75% specificity for malignant lesions and took 0.2 s per prediction with the AI sever. Prediction using a smartphone required 2 s per prediction and showed 100% sensitivity and 97.5% specificity for malignant lesions. CONCLUSIONS: Good-quality predictions were obtained using the AI server. Moreover, the quality of the prediction via the smartphone was slightly better than that on the AI server, which can be safely and inexpensively introduced into HISs.

Human breast tumor derived endothelial cells exhibit distinct biological properties.

BACKGROUND INFORMATION: Excessive angiogenesis characterized by leaky, tortuous, and chaotic vasculature is one of the hallmarks of cancers and is significantly correlated to poor prognosis. Disorganized angiogenesis leads to poor perfusion of anti-cancer drugs and limits access to immune cells. Hence, impeding angiogenesis is one of the attractive therapeutic targets to inhibit progression and metastasis in several solid tumors including breast. RESULTS: We have developed a robust and reproducible method for isolating and ex vivo culture of endothelial cells (EC) derived from non-malignant (Endo-N) and malignant (Endo-T) part from clinically characterized human breast tumors. RT-PCR and immunoblotting analysis indicated that these cells exhibited expression of endothelial specific genes such as PECAM-1 (CD31), Endoglin (CD105), eNOS, VE-cadherin, VCAM1, and MCAM. Vasculogenic mimicry and contamination of progenitor EC recruited in tumors was ruled out by absence of CD133 expression and normal karyotype. Both the cell types showed stable expression of CD31 and CD105 up to seven passages. Furthermore, compared to Endo-N cells, Endo-T cells showed (a) constitutively increased proliferation marked by nearly 36% of cells in mitotic phase, (b) requirement of glutamine for cell survival, (c) pro-migratory phenotype, (d) produced increased number of sprouts in 3D cultures, and (e) resistance to sorafenib. CONCLUSION: Tumor derived EC showed distinct biological properties compared to normal breast EC. SIGNIFICANCE: Our method for isolating endothelial cell types from human breast tumors may be explored to (a) understand cellular and molecular mechanisms, (b) screen anti-angiogenic molecules, and (c) formulate organoid cultures to develop personalized medicine facilitating better clinical management of breast cancers.

Boundary-oriented Network for Automatic Breast Tumor Segmentation in Ultrasound Images.

Breast cancer is considered as the most prevalent cancer. Using ultrasound images is a momentous clinical diagnosis method to locate breast tumors. However, accurate segmentation of breast tumors remains an open problem due to ultrasound artifacts, low contrast, and complicated tumor shapes in ultrasound images. To address this issue, we proposed a boundary-oriented network (BO-Net) for boosting breast tumor segmentation in ultrasound images. The BO-Net boosts tumor segmentation performance from two perspectives. Firstly, a boundary-oriented module (BOM) was designed to capture the weak boundaries of breast tumors by learning additional breast tumor boundary maps. Second, we focus on enhanced feature extraction, which takes advantage of the Atrous Spatial Pyramid Pooling (ASPP) module and Squeeze-and-Excitation (SE) block to obtain multi-scale and efficient feature information. We evaluate our network on two public datasets: Dataset B and BUSI. For the Dataset B, our network achieves 0.8685 in Dice, 0.7846 in Jaccard, 0.8604 in Precision, 0.9078 in Recall, and 0.9928 in Specificity. For the BUSI dataset, our network achieves 0.7954 in Dice, 0.7033 in Jaccard, 0.8275 in Precision, 0.8251 in Recall, and 0.9814 in Specificity. Experimental results show that BO-Net outperforms the state-of-the-art segmentation methods for breast tumor segmentation in ultrasound images. It demonstrates that focusing on boundary and feature enhancement creates more efficient and robust breast tumor segmentation.

Induction of alternative NF-κB within TAg-induced basal mammary tumors in activation-resistant inhibitor of κ-B kinase (IKKα) mutant mice.

BACKGROUND: The alternative NF-κB pathway is activated by the NF-κB-inducing kinase (NIK) mediated phosphorylation of the inhibitor of κ-B kinase α (IKKα). IKKα then phosphorylates p100/NFKB2 to result in its processing to the active p52 subunit. Evidence suggests that basal breast cancers originate within a subpopulation of luminal progenitor cells which is expanded by signaling to IKKα. OBJECTIVE: To determine the role of IKKα in the development of basal tumors. METHODS: Kinase dead IkkαAA/AA mice were crossed with the C3(1)-TAg mouse model of basal mammary cancer. Tumor growth and tumor numbers in WT and IkkαAA/AA mice were assessed and immunopathology, p52 expression and stem/progenitor 3D colony forming assays were performed. Nik-/- mammary glands were isolated and mammary colonies were characterized. RESULTS: While tumor growth was slower than in WT mice, IkkαAA/AA tumor numbers and pathology were indistinguishable from WT tumors. Both WT and IkkαAA/AA tumors expressed p52 except those IkkαAA/AA tumors where NIK, IKKαAA/AA and ErbB2 were undetectable. Colonies formed by WT and IkkαAA/AA mammary cells were nearly all luminal/acinar however, colony numbers and sizes derived from IkkαAA/AA cells were reduced. In contrast to IkkαAA/AA mice, virgin Nik-/- mammary glands were poorly developed and colonies were primarily derived from undifferentiated bipotent progenitor cells. CONCLUSIONS: C3(1)-TAg induced mammary tumors express p100/p52 even without functional IKKα. Therefore the development of basal-like mammary cancer does not strictly rely on IKKα activation. Signal-induced stabilization of NIK may be sufficient to mediate processing of p100NFKB2 which can then support basal-like mammary tumor formation. Lastly, in contrast to the pregnancy specific role of IKKα in lobuloalveogenesis, NIK is obligatory for normal mammary gland development.

A modified source-detector configuration for the discrimination between normal and diseased human breast based on the continuous-wave diffuse optical imaging approach: a simulation study.

Breast tumors are among the most common types of tumors that can affect both genders. It may spread to the whole breast without any symptoms. Therefore, the early detection and accurate diagnosis of breast tumors are significantly important. Current approaches for breast cancer screening such as positron emission tomography (PET) and magnetic resonance imaging (MRI) have some limitations of being time and money-consuming. In addition, mammography screening is not recommended for women under forty. Consequently, optical techniques have been introduced as safe and functional alternatives. Diffuse optical imaging is a non-invasive imaging technique that utilizes near-infrared light to examine biological tissues based on measuring the optical transmission and/or reflection at various locations on the tissue surface. In this paper, we propose a modified arrangement between the laser source and the detectors for distinguishing tumors from normal breast tissue. A three-dimensional model of the normal human breast with three types of tumors is developed using a COMSOL simulation software based on the finite element solution of Helmholtz equation to estimate optical fluence distribution. The breast model consists of four layers: skin, fat, glandular, and muscle, where the tumor is included in the glandular layer. Different wavelengths were used to determine the most proper wavelength for the discrimination between the normal tissue and tumor. The obtained results were verified using the receiver operating characteristic (ROC) method. The resultant fluence images show different features between normal breast and breast with tumor especially using 600-nm incident laser as demonstrated by the obtained ROC curves.

Efficient System for Delimitation of Benign and Malignant Breast Masses.

In this study, a high-performing scheme is introduced to delimit benign and malignant masses in breast ultrasound images. The proposal is built upon by the Nonlocal Means filter for image quality improvement, an Intuitionistic Fuzzy C-Means local clustering algorithm for superpixel generation with high adherence to the edges, and the DBSCAN algorithm for the global clustering of those superpixels in order to delimit masses' regions. The empirical study was performed using two datasets, both with benign and malignant breast tumors. The quantitative results with respect to the BUSI dataset were JSC≥0.907, DM≥0.913, HD≥7.025, and MCR≤6.431 for benign masses and JSC≥0.897, DM≥0.900, HD≥8.666, and MCR≤8.016 for malignant ones, while the MID dataset resulted in JSC≥0.890, DM≥0.905, HD≥8.370, and MCR≤7.241 along with JSC≥0.881, DM≥0.898, HD≥8.865, and MCR≤7.808 for benign and malignant masses, respectively. These numerical results revealed that our proposal outperformed all the evaluated comparative state-of-the-art methods in mass delimitation. This is confirmed by the visual results since the segmented regions had a better edge delimitation.

Diagnostic value of diffusion-weighted imaging with synthetic b-values in breast tumors: comparison with dynamic contrast-enhanced and multiparametric MRI.

OBJECTIVES: To assess DWI for tumor visibility and breast cancer detection by the addition of different synthetic b-values. METHODS: Eighty-four consecutive women who underwent a breast-multiparametric-MRI (mpMRI) with enhancing lesions on DCE-MRI (BI-RADS 2-5) were included in this IRB-approved retrospective study from September 2018 to March 2019. Three readers evaluated DW acquired b-800 and synthetic b-1000, b-1200, b-1500, and b-1800 s/mm2 images for lesion visibility and preferred b-value based on lesion conspicuity. Image quality (1-3 scores) and breast composition (BI-RADS) were also recorded. Diagnostic parameters for DWI were determined using a 1-5 malignancy score based on qualitative imaging parameters (acquired + preferred synthetic b-values) and ADC values. BI-RADS classification was used for DCE-MRI and quantitative ADC values + BI-RADS were used for mpMRI. RESULTS: Sixty-four malignant (average = 23 mm) and 39 benign (average = 8 mm) lesions were found in 80 women. Although b-800 achieved the best image quality score, synthetic b-values 1200-1500 s/mm2 were preferred for lesion conspicuity, especially in dense breast. b-800 and synthetic b-1000/b-1200 s/mm2 values allowed the visualization of 84-90% of cancers visible with DCE-MRI performing better than b-1500/b-1800 s/mm2. DWI was more specific (86.3% vs 65.7%, p < 0.001) but less sensitive (62.8% vs 90%, p < 0.001) and accurate (71% vs 80.7%, p = 0.003) than DCE-MRI for breast cancer detection, where mpMRI was the most accurate modality accounting for less false positive cases. CONCLUSION: The addition of synthetic b-values enhances tumor conspicuity and could potentially improve tumor visualization particularly in dense breast. However, its supportive role for DWI breast cancer detection is still not definite. KEY POINTS: • The addition of synthetic b-values (1200-1500 s/mm2) to acquired DWI afforded a better lesion conspicuity without increasing acquisition time and was particularly useful in dense breasts. • Despite the use of synthetic b-values, DWI was less sensitive and accurate than DCE-MRI for breast cancer detection. • A multiparametric MRI modality still remains the best approach having the highest accuracy for breast cancer detection and thus reducing the number of unnecessary biopsies.

Targeting the purinergic pathway in breast cancer and its therapeutic applications.

Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

Assessment of the Grisotti oncoplastic procedure for the management of central breast tumors.

INTRODUCTION: The Grisotti technique consists to excise central breast tumor with nipple areolar and mobilize a dermo-glandular flap which is de-epithelized in order to reshape the breast and recreate an areola. The objective was to assess oncological results, postoperative side-effects, and patient and surgeon satisfaction rates resulting from this technique. MATERIALS AND METHODS: From September 2016 to December 2019, 38 patients have been treated with a central breast tumor using the Grisotti technique. RESULTS: The mean age was 61.6 ± 11. The median body mass index was 27 kg/m² [20-42]. Thirty one patients benefited from a sentinel lymph node dissection. Preoperative histology found a majority of invasive ductal carcinomas (IDC) (71%). There were no intraoperative complications, and the average operating time was 90 min [60-200]. Postoperative histology found IDC associated with ductal carcinoma in situ in 28 patients. The surgical margins were invaded in two patients (reoperated by mastectomy after adjuvant treatment) and invasion of a margin of less than 1 mm in another six patients (supplemented by re-excision). The main postoperative complications were an abscess of the operating site and a partial necrosis of the neo-areola. The appearance of the breasts after radiotherapy gives a high satisfaction rate, both for patients and for surgeons. CONCLUSION: The Grisotti technique is an easily reproducible procedure without major complications. It makes it possible to perform a carcinological satisfactory central lumpectomy, correction of the central glandular defect, and reconstruction of a new areola.

Ret Receptor Has Distinct Alterations and Functions in Breast Cancer.

Ret receptor tyrosine kinase is a proto-oncogene that participates in development of various cancers. Several independent studies have recently identified Ret as a key player in breast cancer. Although Ret overexpression and function have been under investigation, mainly in estrogen receptor positive breast cancer, a more comprehensive analysis of the impact of recurring Ret alterations in breast cancer is needed. This review consolidates the current knowledge of Ret alterations and their potential effects in breast cancer. We discuss and integrate data on Ret changes in different breast cancer subtypes and potential function in progression, as well as the participation of distinct Ret network signaling partners in these processes. We propose that it will be essential to define a shared molecular feature of tumors with alteration in Ret receptor, be this at the genetic level or via overexpression in order to design effective therapies to target the Ret pathway. Here we review experimental evidence from basic research and pre-clinical studies concentrating on Ret alterations as potential biomarkers for recurrence, and we discuss the possibility that targeting the Ret pathway might in the future become a treatment for breast cancer.

miRNA expression profiling of hereditary breast tumors from BRCA1- and BRCA2-germline mutation carriers in Brazil.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene expression regulation and have been described as key regulators of carcinogenesis. Aberrant miRNA expression has been frequently reported in sporadic breast cancers, but few studies have focused on profiling hereditary breast cancers. In this study, we aimed to identify specific miRNA signatures in hereditary breast tumors and to compare with sporadic breast cancer and normal breast tissues. METHODS: Global miRNA expression profiling using NanoString technology was performed on 43 hereditary breast tumors (15 BRCA1, 14 BRCA2, and 14 BRCAX), 23 sporadic breast tumors and 8 normal breast tissues. These normal breast tissues derived from BRCA1- and BRCA2- mutation carriers (n = 5) and non-mutation carriers (n = 3). Subsequently, we performed receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performance of differentially expressed miRNAs. Putative target genes of each miRNAs considered as potential biomarkers were identified using miRDIP platform and used for pathway enrichment analysis. RESULTS: miRNA expression analyses identified several profiles that were specific to hereditary breast cancers. A total of 25 miRNAs were found to be differentially expressed (fold change: > 2.0 and p < 0.05) and considered as potential biomarkers (area under the curve > 0.75) in hereditary breast tumors compared to normal breast tissues, with an expressive upregulation among BRCAX cases. Furthermore, bioinformatic analysis revealed that these miRNAs shared target genes involved in ErbB, FoxO, and PI3K-Akt signaling pathways. CONCLUSIONS: Our results showed that miRNA expression profiling can differentiate hereditary from sporadic breast tumors and normal breast tissues. These miRNAs were remarkably deregulated in BRCAX hereditary breast cancers. Therefore, miRNA signatures can be used as potential novel diagnostic biomarkers for the prediction of BRCA1/2- germline mutations and may be useful for future clinical management.

Transaxillary endoscopic excision of benign breast tumors, early institution experience.

BACKGROUND AND AIM: Benign breast diseases are one of the most common diseases in females. An important goal in its treatment should be cosmesis, so a new minimally invasive technique has advanced. One of these techniques is the transaxillary endoscopic resection. The aim of this study was to assess the feasibility, safety, operative time, postoperative pain, hospital stay, and cosmetic outcome of this transaxillary approach. METHODS: This study was carried out on 40 female patients presented with benign breast tumors in the surgical oncology unit at the General Surgery Department, Tanta University Hospital during the period from January 2018 to January 2019. The patients included in the study aged ≥18 years, had solitary or multiple benign breast tumors, located at any breast quadrant. The patients subjected to transaxillary endoscopic excision of the tumors. RESULTS: The age of the patients ranged from 20 to 49 years with a mean age of 32 years. 60% of the lesions located in the upper half of the breast. Fibroadenoma was the most common finding in 80% of the patients, 60% of the patients had solitary tumor. The operative time ranged from 42 to 105 minutes with a mean of 61.4 minutes. 88.8% of the patients considered the cosmetic outcome excellent. CONCLUSION: Endoscopic transaxillary excision of benign breast tumors is safe, feasible and has excellent cosmetic outcomes with high patient's satisfaction.

Breast Elastography: How to Perform and Integrate Into a "Best-Practice" Patient Treatment Algorithm.

Breast elastography has been available for more than 15 years but is not widely incorporated into clinical practice. Many publications report extremely high accuracy for various breast elastographic techniques. However, results in the literature are extremely variable. This variability is most likely due to variations in technique, a relatively steep learning curve, and variability in methods between vendors. This article describes our protocol for performing breast elastography using both strain elastography and shear wave elastography, which produces high sensitivity and specificity. Additionally, we will describe the most commonly known false-positive and false-negative lesions as well as how to detect them.

Breast Tumor Diagnosis Using Finite-Element Modeling Based on Clinical in vivo Elastographic Data.

OBJECTIVES: This study exploited finite-element modeling (FEM) to simulate breast tissue multicompression during ultrasound elastography to classify breast tumors based on their nonlinear biomechanical properties. METHODS: Numeric simulations were first calculated by using 3-dimensional (3D) virtual models with an assumed tumor's geometric dimensions but with actual material properties to test and validate the FEM. Further numeric simulations were used to construct 3D models based on in vivo experimental data to verify our models. The models were designed for each individual in vivo case, emphasizing the geometry, position, and biomechanical properties of the breast tissue. At different compression levels, tissue strains were analyzed between the tumors and the background normal tissues to explore their nonlinearity and classify the tumor type. Tumor classification parameters were deduced by using a power-law relationship between the applied compressive forces and strain differences. RESULTS: Classification parameters were compared between benign and malignant tumors, for which they were found to be statistically significant in classifying the tumor types (P < .05) by both the validation and verification of FEM. We compared the classification parameters between the in vivo and FEM classifications, for which they were found to be strongly correlated (R = 0.875; P < .001), with no statistical differences between their outcomes (P = .909). CONCLUSIONS: Good agreement between the model outcomes and the in vivo diagnostics was reported. The implemented models were validated and verified. The introduced 3D modeling method may augment elastographic methods to preliminary classify breast tumors at an early stage.

Immune Checkpoint Blockade Mediated by a Small-Molecule Nanoinhibitor Targeting the PD-1/PD-L1 Pathway Synergizes with Photodynamic Therapy to Elicit Antitumor Immunity and Antimetastatic Effects on Breast Cancer.

Targeting programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) immunologic checkpoint blockade with monoclonal antibodies has achieved recent clinical success in antitumor therapy. However, therapeutic antibodies exhibit several issues such as limited tumor penetration, immunogenicity, and costly production. Here, Bristol-Myers Squibb nanoparticles (NPs) are prepared using a reprecipitation method. The NPs have advantages including passive targeting, hydrophilic and nontoxic features, and a 100% drug loading rate. BMS-202 is a small-molecule inhibitor of the PD-1/PD-L1 interaction that is developed by BMS. Transfer of BMS-202 NPs to 4T1 tumor-bearing mice results in markedly slower tumor growth to the same degree as treatment with anti-PD-L1 monoclonal antibody (α-PD-L1). Consistently, the combination of Ce6 NPs with BMS-202 NPs or α-PD-L1 in parallel shows more efficacious antitumor and antimetastatic effects, accompanied by enhanced dendritic cell maturation and infiltration of antigen-specific T cells into the tumors. Thus, inhibition rates of primary and distant tumors reach >90%. In addition, BMS-202 NPs are able to attack spreading metastatic lung tumors and offer immune-memory protection to prevent tumor relapse. These results indicate that BMS-202 NPs possess effects similar to α-PD-L1 in the therapies of 4T1 tumors. Therefore, this work reveals the possibility of replacing the antibody used in immunotherapy for tumors with BMS-202 NPs.

Diagnostic Performance and Accuracy of the 3 Interpreting Methods of Breast Strain Elastography: A Systematic Review and Meta-analysis.

There are 3 methods of interpreting breast strain elastography: the elastographic-to-B-mode length ratio (E/B), a 5-point color scale (5P), and the strain ratio (SR). This meta-analysis assessed which method is superior to the others. A systematic search of the medical literature was performed in July 2017. Studies were eligible for inclusion if they fulfilled the following criteria: (1) had biopsy-proven or long-term stability as the reference standard; (2) used either the E/B, 5P, or SR to interpret results; and (3) had at least 50 cases. A total of 220 records were retrieved; 60 full-text articles were examined, and 46 were included in the meta-analysis. Publication years ranged from 2007 and 2017. The quality of studies was generally high. The mean age of women was 48 years; 12,398 lesions (4242 malignant) were analyzed. For the 5P method, the sensitivity was 77%; specificity, 87%; positive likelihood ratio (LR), 5.3; and negative LR, 0.24. For the SR method, sensitivity was 87%; specificity, 81%; positive LR, 4.8; and negative LR, 0.16. For the E/B method, sensitivity was 96%; specificity, 88%; positive LR, 7.1; and negative LR, 0.03. Of the 3 methods, the E/B had the highest sensitivity, and the E/B and 5P had the highest specificity. With a negative LR of 0.03, the E/B method can downgrade lesions with a pretest probability of 50% to a 2% probability of malignancy.