Search Results (810)

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Carboxypeptidase A4 (CPA4) is an exopeptidase that cleaves peptide bonds at the C-terminal domain within peptides and proteins. It preferentially cleaves peptides with terminal aromatic or branched chain amino acid residues such as phenylalanine, tryptophan, or leucine. CPA4 was first discovered in prostate cancer cells, but it is now known to be expressed in various tissues throughout the body. Its physiologic expression is governed by latexin, a noncompetitive endogenous inhibitor of CPA4. Nevertheless, the overexpression of CPA4 has been associated with the progression and aggressiveness of many malignancies, including prostate, pancreatic, breast and lung cancer, to name a few. CPA4’s role in cancer has been attributed to its disruption of many cellular signaling pathways, e.g., PI3K-AKT-mTOR, STAT3-ERK, AKT-cMyc, GPCR, and estrogen signaling. The dysregulation of these pathways by CPA4 could be responsible for inducing epithelial--mesenchymal transition (EMT), tumor invasion and drug resistance. Although CPA4 has been found to regulate cancer aggressiveness and poor prognosis, no comprehensive review summarizing the role of CPA4 in cancer is available so far. In this review, we provide a brief description of peptidases, their classification, history of CPA4, mechanism of action of CPA4 as a peptidase, its expression in various tissues, including cancers, its role in various tumor types, the associated molecular pathways and cellular processes. We further discuss the limitations of current literature linking CPA4 to cancers and challenges that prevent using CPA4 as a biomarker for cancer aggressiveness and predicting drug response and highlight a number of future strategies that can help to overcome the limitations. Full article

Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. While extensively characterized in breast MRI, the role of BPE in contrast-enhanced mammography (CEM) remains uncertain due to inconsistent findings regarding its correlation with breast density and cancer risk. Unlike breast density—standardized through the ACR BI-RADS lexicon—BPE lacks a uniform classification system in CEM, leading to variability in clinical interpretation and research outcomes. To address this gap, we introduce the BPE-CEM Standard Scale (BCSS), a structured four-tiered classification system specifically tailored to the two-dimensional characteristics of CEM, aiming to improve consistency and diagnostic alignment in BPE evaluation. Materials and Methods: In this retrospective single-center study, 213 patients who underwent mammography (MG), ultrasound (US), and contrast-enhanced mammography (CEM) between May 2022 and June 2023 at the “A. Perrino” Hospital in Brindisi were included. Breast density was classified according to ACR BI-RADS (categories A–D). BPE was categorized into four levels: Minimal (< 10% enhancement), Light (10–25%), Moderate (25–50%), and Marked (> 50%). Three radiologists independently assessed BPE in a subset of 50 randomly selected cases to evaluate inter-observer agreement using Cohen’s kappa. Correlations between BPE, breast density, and age were examined through regression analysis. Results: BPE was Minimal in 57% of patients, Light in 31%, Moderate in 10%, and Marked in 2%. A significant positive association was found between higher breast density (BI-RADS C–D) and increased BPE (p < 0.05), whereas lower-density breasts (A–B) were predominantly associated with minimal or light BPE. Regression analysis confirmed a modest but statistically significant association between breast density and BPE (R² = 0.144), while age showed no significant effect. Inter-observer agreement for BPE categorization using the BCSS was excellent (κ = 0.85; 95% CI: 0.78–0.92), supporting its reproducibility. Conclusions: Our findings indicate that breast density is a key determinant of BPE in CEM. The proposed BCSS offers a reproducible, four-level framework for standardized BPE assessment tailored to the imaging characteristics of CEM. By reducing variability in interpretation, the BCSS has the potential to improve diagnostic consistency and facilitate integration of BPE into personalized breast cancer risk models. Further prospective multicenter studies are needed to validate this classification and assess its clinical impact. Full article

Accurate classification of breast cancer histopathology images is critical for early diagnosis and treatment planning. Yet, conventional deep learning models face significant challenges under limited annotation scenarios due to their reliance on large-scale labeled datasets. To address this, we propose Dynamic Cross-Scale Swin Transformer (DCS-ST), a robust and efficient framework tailored for histopathology image classification with scarce annotations. Specifically, DCS-ST integrates a dynamic window predictor and a cross-scale attention module to enhance multi-scale feature representation and interaction while employing a semi-supervised learning strategy based on pseudo-labeling and denoising to exploit unlabeled data effectively. This design enables the model to adaptively attend to diverse tissue structures and pathological patterns while maintaining classification stability. Extensive experiments on three public datasets—BreakHis, Mini-DDSM, and ICIAR2018—demonstrate that DCS-ST consistently outperforms existing state-of-the-art methods across various magnifications and classification tasks, achieving superior quantitative results and reliable visual classification. Furthermore, empirical evaluations validate its strong generalization capability and practical potential for real-world weakly-supervised medical image analysis. Full article

Breast cancer continues to be one of the leading causes of women’s deaths around the world, and this has emphasized the necessity to have novel and interpretable diagnostic models. This work offers a clear learning deep learning model that integrates the mobility of MobileNet and two bio-driven optimization operators, the Firefly Algorithm (FLA) and Dingo Optimization Algorithm (DOA), in an effort to boost classification appreciation and the convergence of the model. The suggested model demonstrated excellent findings as the DOA-optimized MobileNet acquired the highest performance of 98.96 percent accuracy on the fusion test, and the FLA-optimized MobileNet scaled up to 98.06 percent and 95.44 percent accuracies on mammographic and ultrasound tests, respectively. Further to good quantitative results, Grad-CAM visualizations indeed showed clinically consistent localization of the lesions, which strengthened the interpretability and model diagnostic reliability of Grad-CAM. These results show that lightweight, compact CNNs can be used to do high-performance, multimodal breast cancer diagnosis. Full article

Background/Objectives: The implementation of polygenic scores (PGSs) and multifactorial risk assessments (MFRAs) has the potential to enhance breast cancer risk stratification, particularly in carriers of moderate-penetrance pathogenic variants (PVs), whose risk profiles often remain unclear if testing is limited to monogenic risk factors. Methods: To enhance breast cancer risk stratification, we included the BCAC313 polygenic score, together with MFRA, for carriers of moderate-penetrance pathogenic variants (PVs) during routine diagnostics and assessed its effect on the classification of patients’ risk categories in a real-world cohort at our center in its first year of implementation. Seventeen carriers with PVs in moderate-risk breast cancer genes were included in this study. Thirteen of them qualified for analysis for a full MFRA, including PGS, according to ancestry estimation and clinical criteria. The MFRA was performed using the CanRisk tool, which incorporates clinical, lifestyle, familial, and genetic data, including the BCAC313 score. Results: PGS z-scores were significantly higher in breast cancer patients compared to the unaffected control cohort (p = 0.016). The MFRA, including PGS, increased risk estimates for contralateral breast cancer in seven of eight patients with breast cancer and for primary breast cancer in three of five healthy carriers, compared to the risk conferred by the MFRA and moderate-penetrance pathogenic variant alone. Risk estimates varied widely, demonstrating the value of MFRA in personalized care. In five cases, one with a CHEK2-PV and four with an ATM-PV, the modified risk assessment contributed to the surgical decision for a prophylactic mastectomy. Conclusions: The MFRA, including PGS, provides the clinically meaningful refinement of breast cancer risk estimates in individuals with moderate-risk PVs. Personalized risk predictions can inform clinical management and support decision-making, which highlights the utility of this approach in clinical practice. Full article

Breast cancer (BRCA) remains a significant cause of mortality among women, particularly in developing and underdeveloped regions, where early detection is crucial for effective treatment. This research introduces an innovative hybrid model that combines Improved Grey Wolf Optimizer (IGWO) with the Seagull Optimization Algorithm (SOA), forming the IGWO–SOA technique to enhance BRCA detection accuracy. The hybrid model draws inspiration from the adaptive and strategic behaviors of seagulls, especially their ability to dynamically change attack angles in order to effectively tackle complex global optimization challenges. A deep neural network (DNN) is fine-tuned using this hybrid optimization method to address the challenges of hyperparameter selection and overfitting, which are common in DL approaches for BRCA classification. The proposed IGWO–SOA model demonstrates optimal performance in identifying key attributes that contribute to accurate cancer detection using the CBIS-DDSM dataset. Its effectiveness is validated using performance metrics such as loss, F1-score, precision, accuracy, and recall. Notably, the model achieved an impressive accuracy of 99.4%, outperforming existing methods in the domain. By optimizing both the learning parameters and model structure, this research establishes an advanced deep learning framework built upon the IGWO–SOA approach, presenting a robust and reliable method for early BRCA detection with significant potential to improve diagnostic precision. Full article

Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article

Mammography is the main method for early detection of breast cancer, which is still a major global health concern. However, inter-reader variability and the inherent difficulty of interpreting subtle radiographic features frequently limit the accuracy of diagnosis. A thorough assessment of deep convolutional neural networks (CNNs) for automated mammogram classification is presented in this work, along with the introduction of two innovative multi-view integration techniques: Dual-Branch Ensemble (DBE) and Merged Dual-View (MDV). By setting aside two datasets for out-of-sample testing, we evaluate the generalizability of the model using six different mammography datasets that represent various populations and imaging systems. We compare a number of cutting-edge architectures on both individual and combined datasets, including ResNet, DenseNet, EfficientNet, MobileNet, Vision Transformers, and VGG19. Both MDV and DBE strategies improve classification performance, according to experimental results. VGG19 and DenseNet both obtained high ROC AUC scores of 0.9051 and 0.7960 under the MDV approach. DenseNet demonstrated strong performance in the DBE setting, achieving a ROC AUC of 0.8033, while ResNet50 recorded a ROC AUC of 0.8042. These enhancements demonstrate how beneficial multi-view fusion is for boosting model robustness. The impact of domain shift is further highlighted by generalization tests, which emphasize the need for diverse datasets in training. These results offer practical advice for improving CNN architectures and integration tactics, which will aid in the creation of trustworthy, broadly applicable AI-assisted breast cancer screening tools. Full article

Background and Objectives: Regional and systemic analgesic techniques, such as erector spinae plane (ESP) block and opioid administration, implemented during cancer surgery, have been shown to influence immune responses and potentially affect cancer outcomes. Surgical stress and analgesic techniques used in cancer surgery—such as regional nerve blocks or systemic opioids—not only affect pain control but also influence immune and inflammatory pathways that may impact cancer progression. To understand the biological consequences of these interventions, metabolomic profiling has emerged as a powerful approach for capturing systemic metabolic and immunological changes, which are particularly relevant in the oncologic perioperative setting. In this study, we examined the impact of the ESP on the metabolomic profile, as well as levels of VEGF, cortisol, and CRP, in addition to its analgesic effects in breast cancer surgery. Materials and Methods: Ninety patients were placed into three different analgesia groups (morphine, ESP, and control groups). Demographic data, ASA classification, comorbidities, surgery types, and pain scores were documented. Blood samples were taken at preoperative hour 0, postoperative hour 1, and postoperative hour 24 (T0, T1, and T24). VEGF, cortisol, and CRP levels were measured, and metabolomic analysis was performed. Results: Study groups were comparable regarding demographic findings, comorbidities, and surgery types (p > 0.05). NRS scores of group ESP were lowest in the first 12 h period (p < 0.01) and ESP block reduced opioid consumption (p < 0.01). VEGF and cortisol levels of group morphine were similar to ESP at T24 (p > 0.05). Group ESP had lower VEGF and cortisol levels than the control at T24 (p = 0.025, p = 0.041, respectively.). The CRP level of group morphine was higher than both ESP and control at T24 (p = 0.022). Metabolites involved in primary bile acid, steroid hormone biosynthesis, amino acid, and glutathione metabolism were changed in group ESP. Conclusions: Metabolites in bile acid biosynthesis and steroid hormone pathways, which play a key role in immune responses, were notably lower in the ESP group. Accordingly, VEGF and cortisol peaks were more moderate in group ESP. In conclusion, we think that ESP block, which provides adequate analgesia, is an acceptable approach in terms of modulating immune responses in breast cancer surgery. Full article

Accurate preoperative distinction between in situ and invasive Breast Cancer (BC) is critical for clinical decision-making and treatment planning. Radiomics and Machine Learning (ML) have shown promise in enhancing diagnostic performance from breast MRI, yet their application to this specific task remains underexplored. The aim of this study was to evaluate the performance of several ML classifiers, trained on radiomic features extracted from DCE–MRI and supported by basic clinical information, for the classification of in situ versus invasive BC lesions. In this study, we retrospectively analysed 71 post-contrast DCE–MRI scans (24 in situ, 47 invasive cases). Radiomic features were extracted from manually segmented tumour regions using the PyRadiomics library, and a limited set of basic clinical variables was also included. Several ML classifiers were evaluated in a Leave-One-Out Cross-Validation (LOOCV) scheme. Feature selection was performed using two different strategies: Minimum Redundancy Maximum Relevance (MRMR), mutual information. Axial 3D rotation was used for data augmentation. Support Vector Machine (SVM), K Nearest Neighbors (KNN), Random Forest (RF), and Extreme Gradient Boosting (XGBoost) were the best-performing models, with an Area Under the Curve (AUC) ranging from 0.77 to 0.81. Notably, KNN achieved the best balance between sensitivity and specificity without the need for data augmentation. Our findings confirm that radiomic features extracted from DCE–MRI, combined with well-validated ML models, can effectively support the differentiation of in situ vs. invasive breast cancer. This approach is quite robust even in small datasets and may aid in improving preoperative planning. Further validation on larger cohorts and integration with additional imaging or clinical data are recommended. Full article

Breast cancer is a leading cause of mortality among women worldwide. Early detection is crucial for increasing patient survival rates. Artificial intelligence, particularly convolutional neural networks (CNNs), has enabled the development of effective diagnostic systems by digitally processing mammograms. CNNs have been widely used for the classification of breast cancer in images, obtaining accurate results similar in many cases to those of medical specialists. This work presents a hybrid feature extraction approach for breast cancer detection that employs variants of EfficientNetV2 network and convenient image representation based on phase features. First, a region of interest (ROI) is extracted from the mammogram. Next, a three-channel image is created using the local phase, amplitude, and orientation features of the ROI. A feature vector is constructed for the processed mammogram using the developed CNN model. The size of the feature vector is reduced using simple statistics, achieving a redundancy suppression of $99.65\%$. The reduced feature vector is classified as either malignant or benign using a classifier ensemble. Experimental results using a training/testing ratio of 70/30 on 15,506 mammography images from three datasets produced an accuracy of $86.28\%$, a precision of $78.75\%$, a recall of $86.14\%$, and an F1-score of $80.09\%$ with the modified EfficientNetV2 model and stacking classifier. However, an accuracy of $93.47\%$, a precision of $87.61\%$, a recall of $93.19\%$, and an F1-score of $90.32\%$ were obtained using only CSAW-M dataset images. Full article

Background/Objectives: In recent years, there has been a significant increase in the number of women with breast cancer. Breast cancer prediction is defined as a medical data analysis and image processing problem. Experts may need artificial intelligence technologies to distinguish between benign and malignant tumors in order to make decisions. When the studies in the literature are examined, it can be seen that applications of deep learning algorithms in the field of medicine have achieved very successful results. Methods: In this study, 11 different deep learning algorithms (Vanilla, ResNet50, ResNet152, VGG16, DenseNet152, MobileNetv2, EfficientB1, NasNet, DenseNet201, ensemble, and Tuned Model) were used. Images of pathological specimens from breast biopsies consisting of two classes, benign and malignant, were used for classification analysis. To limit the computational time and speed up the analysis process, 10,000 images, 6172 IDC-negative and 3828 IDC-positive, were selected. Of the images, 80% were used for training, 10% were used for validation, and 10% were used for testing the trained model. Results: The results demonstrate that DenseNet201 achieved the highest classification accuracy of 89.4%, with a precision of 88.2%, a recall of 84.1%, an F1 score of 86.1%, and an AUC score of 95.8%. Conclusions: In conclusion, this study highlights the potential of deep learning algorithms in breast cancer classification. Future research should focus on integrating multi-modal imaging data, refining ensemble learning methodologies, and expanding dataset diversity to further improve the classification accuracy and real-world clinical applicability. Full article

Background and Objectives: The accuracy of breast cancer diagnosis depends on the concordance between imaging features and pathological findings. While BI-RADS (Breast Imaging Reporting and Data System) provides standardized risk stratification, its correlation with histologic grade and immunohistochemical markers remains underexplored. This study assessed the diagnostic performance of BI-RADS 3, 4, and 5 classifications and their association with tumor grade and markers such as ER, PR, HER2, and Ki-67. Materials and Methods: In this prospective study, 67 women aged 33–82 years (mean 56.4) underwent both mammography and ultrasound. All lesions were biopsied using ultrasound-guided 14G core needles. Imaging characteristics (e.g., margins, echogenicity, calcifications), histopathological subtype, and immunohistochemical data were collected. Statistical methods included logistic regression, Chi-square tests, and Spearman’s correlation to assess associations between BI-RADS, histology, and immunohistochemical markers. Results: BI-RADS 5 lesions showed a 91% malignancy rate. Evaluated features included spiculated margins, pleomorphic microcalcifications, and hypoechoic masses with posterior shadowing, and were correlated with histological and immunohistochemical results. Invasive tumors typically appeared as irregular, hypoechoic masses with posterior shadowing, while mucinous carcinomas mimicked benign features. Higher BI-RADS scores correlated significantly with increased Ki-67 index (ρ = 0.76, p < 0.001). Logistic regression yielded an AUC of 0.877, with 93.8% sensitivity and 80.0% specificity. Conclusions: BI-RADS scoring effectively predicts malignancy and correlates with tumor proliferative markers. Integrating imaging, histopathology, and molecular profiling enhances diagnostic precision and supports risk-adapted clinical management in breast oncology. Full article

Breast cancer remains one of the leading causes of mortality among women worldwide, highlighting the critical need for early and accurate detection methods. Traditional mammography, although widely used, has limitations, including radiation exposure and challenges in detecting early-stage lesions. Electrical Impedance Mammography (EIM) has emerged as a non-invasive and radiation-free alternative that assesses the density and electrical conductivity of breast tissue. EIM images consist of seven layers, each representing different tissue depths, offering a detailed representation of the breast structure. However, analyzing these layers individually can be redundant and complex, making it difficult to identify relevant features for lesion classification. To address this issue, advanced computational techniques are employed for image integration, such as the Root Mean Square ($C_{\mathrm{RMS}}$) Contrast and Contrast-Limited Adaptive Histogram Equalization (CLAHE), combined with the Coefficient of Variation (CV), CLAHE-based fusion, weighted average fusion, Gaussian pyramid fusion, and Wavelet–PCA fusion. Each method enhances the representation of tissue features, optimizing the image quality and diagnostic utility. This study evaluated the impact of these integration techniques on EIM image analysis, aiming to improve the accuracy and reliability of computational diagnostic models for breast cancer detection. According to the obtained results, the best performance was achieved using Wavelet–PCA fusion in combination with XGBoost as a classifier, yielding an accuracy rate of 89.5% and an F1-score of 81.5%. These results are highly encouraging for the further investigation of this topic. Full article