Search Results (20,186)

Background/Objectives: Ki-67 is widely used as an immunohistochemical marker of tumor proliferation in hormone receptor-positive (HR-positive), HER2-negative breast cancer, but its interpretation is limited by variability and uncertain concordance with genomic assays. The Oncotype DX^® Recurrence Score (RS) is a validated multigene assay with established prognostic and predictive utility. This study evaluated the relationship between Ki-67 and RS in clinical practice. Methods: We retrospectively analyzed women in Greece with early-stage estrogen receptor-positive, HER2-negative breast cancer without distant metastasis (pM0) who underwent Oncotype DX testing between 2020 and 2023. Eligible patients were node-negative or postmenopausal with node-positive disease. RS was categorized as low (0–25) or high (>25). Ki-67 was assessed using binary (<20% vs. ≥20%) and three-tier (≤5%, >5–<30%, ≥30%) classifications. Associations were analyzed using correlation, concordance, and non-parametric methods. Results: Among 2967 patients, the median RS was 16, with similar distributions across nodal subgroups. Ki-67 and RS demonstrated a modest positive correlation as continuous variables (R = 0.30, p < 0.001). After stratification, associations with RS were observed only in tumors with high Ki-67 expression, whereas no correlation was detected in low or intermediate groups. RS distributions differed significantly across Ki-67 strata. Overall concordance between Ki-67-based proliferation categories and RS-based genomic risk was 56.2%, with discordant cases in both directions. Conclusions: Ki-67 shows a modest association with Oncotype DX RS, but substantial discordance indicates Ki-67 should not substitute genomic testing in HR-positive/HER2-negative early breast cancer. Full article

To quantify preferences and trade-offs for non-overall survival (OS) endpoints among Canadian adults treated for early-stage cancers, participants completed ten choice sets in a discrete choice experiment. Standard-of-care (SoC) was compared to new treatment profiles defined by five attributes: five-year OS, two-year disease advancement, pathological complete response (pCR), and short- and long-term side effects. SoC attribute levels remained constant across respondents, except OS, which varied. For the new treatment, all attributes except OS (fixed as unknown) varied. Data were analyzed using logistic regression and presented as odds ratios (ORs) with 95% confidence intervals (CIs). Among 103 adults treated for early-stage gastrointestinal (n = 40), breast (n = 32), or lung (n = 31) cancer, median age was 59 (Q1, Q3: 43, 75) years; 46.6% were female. Each 25% decrease in SoC OS was associated with higher odds of choosing the new treatment (OR 3.49; 95% CI 2.82–4.31; p < 0.01). Reductions in disease advancement (OR 1.55; 1.26–1.91; p < 0.01) and mild or no short-term side effects versus severe (OR 6.67; 4.35–10.00) significantly increased selection odds; long-term side effects and pCR showed modest, non-significant influence. When OS data were available for SoC, OS strongly influenced decisions; without OS data for new treatments, participants prioritized disease control and short-term tolerability. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, with treatment resistance, recurrence, and metastasis significantly limiting the effectiveness of conventional therapies. Photodynamic therapy (PDT) has emerged as a minimally invasive and highly selective approach, utilizing photosensitizer-generated reactive oxygen species (ROS) to achieve precise tumor cytotoxicity while preserving surrounding healthy tissue. However, clinical translation of PDT remains constrained by critical biological barriers within the tumor microenvironment, including tumor hypoxia, limited light penetration, poor photosensitizer stability, and inefficient cellular uptake. Antigen-targeted liposomal nanocarriers offer a compelling solution by enabling targeted drug delivery and tumor-specific photosensitizer accumulation, prolonged systemic circulation, and enhanced cellular internalization. Their multifunctional architecture uniquely supports combinational therapeutic strategies, integrating PDT with chemotherapy, photothermal therapy, gene therapy, X-ray-induced photodynamic therapy (X-PDT) and immune checkpoint blockade, thereby amplifying antitumor efficacy and overcoming drug resistance mechanisms. This review comprehensively summarizes recent advances in liposome-based PDT for breast cancer, highlighting multimodal therapeutic integration. Special emphasis is placed on preclinical and emerging clinical outcomes, pilot-scale manufacturing considerations, and strategies to minimize immune clearance. Full article

The worldwide rise in antimicrobial resistance, along with the ongoing prevalence of cancer, underscores the pressing need for novel, safe, and multifunctional therapeutic candidates. Medicinal plants continue to serve as a valuable source of chemically diverse bioactive molecules that modulate multiple biological targets. In this investigation, the preliminary screening of the antibacterial and anticancer activities of an ethanolic extract of Alhagi maurorum (A. maurorum) was comprehensively evaluated using integrated chemical characterization, in vitro bioassays, and in silico approaches. A liquid chromatography–mass spectrometry (LC-MS) analysis demonstrated a rich phytochemical profile including glucosinolates, phenolic acids, gallotannins, fatty acids, alkaloids, carotenoid derivatives, and 2-hexyldecanoic acid-associated constituents. Antibacterial efficacy was assessed by disk diffusion and minimum inhibitory concentration (MIC) testing against Escherichia coli (E. coli ) and Bacillus cereus (B. cereus), with the extract producing inhibition zones similar to those observed with streptomycin. Anticancer effects were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays with MCF-7 breast carcinoma cells and Hs27 normal fibroblasts over 24, 48, and 72 h., revealing a time-dependent, selective decrease in malignant cell viability with relatively limited toxicity towards normal cells. Induction of apoptosis was further verified by propidium iodide (PI) staining. A molecular docking analysis highlighted 2-hexyldecanoic acid as the principal active compound, with a strong binding affinity for critical bacterial targets (GyrA, GyrB, and RpoB). In silico toxicity and ADME (absorption, distribution, metabolism, and excretion) assessments indicated favorable drug-like properties, good gastrointestinal uptake, and acceptable safety profiles. Altogether, these results provide combined experimental and computational support for A. maurorum as a promising source of dual-purpose antibacterial and anticancer agents and lay a mechanistic foundation for subsequent preclinical studies. Full article

Purpose: This paper aimed to identify dosimetric, clinical, and CT-based densitometric predictors of radiation-induced pulmonary events in breast cancer patients treated with moderately hypofractionated radiotherapy. Materials and Methods: A single-institution cohort of 1172 consecutive patients treated with 3D conformal whole-breast radiotherapy (40 Gy/15 fractions) before 2017 was analyzed. Ipsilateral lung DVHs and CT densitometry metrics were extracted. Clinical variables and cardiac calcification (CAC) scores (Agatston_score, CAC_volume, Max_HU_Heart) were included. Univariable and multivariable logistic regressions were performed; collinearity was assessed via Spearman correlation and VIF. Optimal thresholds were derived using the Youden index. Internal validation used bootstrap resampling. Results: After a median follow-up of 6.5 years, 18 patients developed moderate/severe pulmonary events. The univariable analysis showed associations with lung densitometric features (median/mean HU, 10th percentile, the lung volume with HU < −850 (V850)), V37 Gy, lung volume, and CAC scores. Lower lung HU values and larger lung volumes were linked to higher risk. The best models combined V850 (or lung volume) with a CAC metric. The model including V850 > 175 cc and continuous Max_HU_Heart achieved an optimism-corrected AUC of 0.68, with good fit and calibration (Hosmer–Lemeshow p = 0.33, R² = 0.847). Conclusions: The baseline cardiopulmonary status, captured by lung and heart densitometry, predicts pulmonary toxicity better than dosimetry. V850 > 175 cc was associated with a 4-fold higher risk, consistent with air trapping, known as a marker of emphysema. Full article

Background/Objectives: Breast cancer is the most common malignancy in young women, many of whom face fertility impairment due to gonadotoxic treatments and prolonged endocrine therapy. Ovarian tissue cryopreservation (OTC) has emerged as an alternative fertility preservation (FP) strategy, particularly when controlled ovarian stimulation is not feasible. This study aimed to evaluate the role of OTC in breast cancer patients, with the aim of clarifying its current clinical role and future perspectives within fertility preservation counselling for this population. Methods: A structured SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis was conducted based on the current literature, addressing clinical efficacy, safety, and applicability of OTC in breast cancer patients. Results: Key strengths of OTC include the absence of delay in cancer treatment and the potential to restore both endocrine and reproductive function. However, limitations include the need for surgery, the theoretical risk of reintroducing malignant cells, and variable, less predictable reproductive outcomes compared with gamete-based strategies. Opportunities lie in advances in cryopreservation, transplantation techniques, and integration with in vitro maturation. Major threats include limited data in breast cancer-specific populations, challenges in BRCA mutation carriers, and low utilization rates affecting cost-effectiveness and healthcare sustainability. Conclusions: OTC represents a valuable complementary FP option for selected breast cancer patients, particularly in urgent settings. Despite promising outcomes, its use should remain individualized within multidisciplinary counseling, considering patient-specific oncological and reproductive factors, while further research is needed to clarify long-term safety and efficacy. Full article

Aerogels derived from microbial exopolysaccharides are useful in the food, pharmaceutical, and environmental sectors, but their application in anticancer therapy is constrained by inadequate characterization, especially regarding effects on normal cells. This study used ethanol precipitation and trichloroacetic acid deproteinization to extract crude exopolysaccharide from the fermentation broth of Bacillus amyloliquefaciens SQ-2. The pure fraction, EPS-3791, was obtained using Sephadex G-100 gel filtration chromatography and DEAE cellulose ion exchange. The weight–average molecular weight of EPS-3791 was 64.4kDa. Monosaccharide analysis indicated fructan as the dominant component, which was consistent with the results of methylation analysis and NMR spectroscopy, confirming that EPS-3791 is a fructan mainly linked by →1)–Fruf–(2→bonds. UV scanning indicated high purity. FTIR analysis revealed functional groups including hydroxyl, carbonyl, and C–O–C groups. EPS-3791 exhibited a porous three-dimensional network morphology by SEM, with a decomposition temperature of 191.61 °C by TGA. Additionally, aerogels were prepared by freeze drying. EPS-3791 aerogels demonstrated minimal cytotoxicity to normal L929 cells while inhibiting the growth of human lung cancer A549, breast cancer MCF–7, and cervical cancer HeLa cells in a dose-dependent manner. Scratch wound healing experiments revealed that EPS-3791 aerogels hindered HeLa cell migration while promoting L929 wound closure. These findings identify EPS-3791 as a fructan-type exopolysaccharide aerogel with specific anticancer properties. Full article

Breast cancer is a type of cancer with the highest incidence and mortality rates among women. PD-L1 suppresses the proliferation and activation of T cells, thereby enabling cancer cells to evade immune surveillance and facilitating tumor progression. Micheliolide (MCL) is a guaianolide-type sesquiterpene lactone with broad biological activities. Our results revealed that radiation upregulates PD-L1 expression in breast cancer cells, while MCL pretreatment can inhibit this effect. Bioinformatics analysis combined with shRNA interference experiments confirmed that radiation upregulates PD-L1 by activating the IRF1-STAT1 signaling pathway, while MCL represses PD-L1 transcription by suppressing this pathway. In addition, MCL also downregulates PD-L1 protein level through accelerating proteasomal degradation of PD-L1. In vivo experiments demonstrated that MCL combined with radiotherapy significantly inhibits the growth of syngeneic tumors and increases intratumoral CD8⁺ T cell infiltration and the frequencies of granzyme B-positive cells. Taken together, our results indicate that MCL enhances T-cell-mediated antitumor immunity and improves radiotherapy efficacy through inhibiting IRF1-STAT1 signaling pathway-driven PD-L1 transcription and promoting PD-L1 protein degradation. This study provides a theoretical basis for the clinical application of MCL as an immunomodulator and radiosensitizer. Full article

Background: The blood–brain barrier (BBB) separates the circulation from the central nervous system (CNS) and serves to maintain brain homeostasis. The BBB comprises highly specialized brain endothelial cells (BECs) with unique properties that allow the BBB to maintain strict regulation of molecules entering and exiting the CNS. These characteristics include tight junctions, low endocytosis rates, and efflux and nutrient transporters. Breast cancer resistance protein (BCRP) is an efflux transporter found at the BBB that plays a key role in protecting the CNS. Together with other efflux transporters, BCRP contributes to multidrug-resistant cancers and difficulty delivering drugs and therapeutics to the brain and other organs. Methods: Using the hCMEC/D3 line, we utilized BCRP substrate rosuvastatin to effectively select for cells expressing high amounts of BCRP, thus generating hCMEC/D3-BCRP. To assess protein abundance, we utilized flow cytometry and confirmed expression via qPCR. To investigate BCRP efflux function in evolved hCMEC/D3-BCRP, we performed substrate accumulation assays with BCRP and P-gp substrates. Results: We found hCMEC/D3-BCRP had increased BCRP abundance and expression relative to parent hCMEC/D3. We also observed an increase in BCRP function via substrate accumulation of two BCRP substrates compared to parent hCMEC/D3. Conclusions: BCRP serves a protective role within the BBB and is a major hurdle in drug delivery. We generated a BCRP overexpression BEC cell line (hCMEC/D3-BCRP) under the influence of endogenous promoters. This cell line can be used to further investigate the role of BCRP in BECs and utilized in efflux transport studies. Full article

Breast cancer histopathological image classification remains a challenging task because reliable diagnosis depends on both fine-grained local lesion characteristics and multi-scale global tissue structures. However, current deep learning approaches often face challenges in effectively integrating these complementary cues, particularly in the presence of staining variations, ambiguous lesion boundaries, and limited annotated datasets. To address these challenges, we propose a novel method called UNI-Phase-Dual Network (UPDNet). This approach enhances the detection of stable lesion boundaries and subtle patterns by incorporating phase congruency, while combining it with global tissue information using the UNI foundation model. The method utilizes two branches to process features from different perspectives, one focusing on fine details and the other capturing broader context. Additionally, we apply a fine-tuning strategy that improves generalization and reduces overfitting in scenarios with small datasets. Experiments on three widely used breast cancer datasets, BRACS, BreakHis, and BACH, demonstrate that UPDNet significantly outperforms existing methods. Specifically, on the 7-class BRACS task, UPDNet achieves 68.58% accuracy, which is a 2.21% improvement over previous methods, and an increase of 1.48% in the weighted F1 score. These results demonstrate the strong potential of UPDNet in breast cancer histopathological image classification. Full article

Healthcare analytics is often limited by data silos and strict privacy requirements, which make it difficult to share patient-level records across organisations and to build robust predictive models. Federated learning (FL) provides an alternative by keeping data local and exchanging model updates instead of raw records. However, many existing FL solutions remain difficult to deploy in healthcare settings, as they provide limited support for auditability, governance-oriented evidence, and system-level transparency. This paper presents MediVault, an auditable and security-aware federated learning-based system for privacy-preserving healthcare collaboration. MediVault combines round-based federated training, prototype-level protected update exchange, audit-ready telemetry, and an interactive dashboard that exposes non-sensitive evidence of collaboration, model progress, and protocol execution. In addition, the system supports controlled reporting to improve stakeholder communication during pilot deployments. We evaluate MediVault on two public healthcare classification datasets, Breast Cancer Wisconsin (Diagnostic) and Heart Disease, under IID and label-skewed Non-IID settings. Experiments are conducted using logistic regression, linear SVM, and an additional lightweight MLP under matched settings. The observed results suggest that federated training remains competitive with centralised training under the evaluated settings. A prototype-level overhead analysis further shows that protected update exchange introduces measurable computational and communication costs, especially for larger update vectors. These findings indicate that MediVault can support initial system-level validation of auditable, privacy-preserving healthcare FL workflows, while further work is needed for larger-scale deployment, stronger adversarial evaluation, and real-world clinical validation. Full article

Breast cancer is one of the leading causes of cancer deaths in women worldwide. Neoadjuvant chemotherapy (NACT) has increased rates of breast-conserving procedures and enabled the identification of patients with a particularly poor prognosis. Achieving a pathological complete response (pCR), an indicator of NACT efficacy, contrasts with residual disease (RD), which identifies patients at higher risk of recurrence. This review provides an overview of current evidence on the clinical and prognostic significance of pCR and RD in patients receiving NACT for breast cancer. The analysis is based on data from randomized clinical trials, meta-analyses, and current clinical guidelines for contemporary systemic treatment. Pathological complete response varies according to tumor subtype, with the highest rates observed in triple-negative and non-luminal HER2-positive breast cancer. In HER2-positive disease, the combination of chemotherapy with HER2-targeted therapies increases pCR rates, while the presence of RD supports escalation of postoperative treatment with antibody–drug conjugates. In triple-negative breast cancer (TNBC), the inclusion of platinum agents and immune checkpoint inhibitors improves treatment efficacy. In HER2-negative breast cancer and germline BRCA1/2 mutations, adjuvant PARP inhibitors improve survival independently of pCR, highlighting the complex relationship between pathological response and prognosis. Immunotherapy and targeted therapies are used alongside standard chemotherapy and hormone therapy in perioperative treatment. Further research is required to refine response assessment, integrate new biomarkers such as circulating tumor DNA (ctDNA), and optimize treatment selection, while clarifying the significance of reassessing hormone receptor and HER2 status in residual disease and its impact on subsequent treatment decisions. Full article

Background/Objectives: The clinical management of ductal carcinoma in situ (DCIS) remains controversial due to its heterogeneous biological behavior and uncertain risk of progression. Standard treatment often includes surgery and radiotherapy, although the actual recurrence risk varies considerably among patients. This study aimed to evaluate recurrence patterns and associated clinicopathological factors in a large single-center cohort of patients with pure DCIS. Methods: We retrospectively analyzed 403 patients with histologically confirmed pure DCIS treated with breast-conserving surgery or mastectomy between 2016 and 2023. Clinical, imaging, pathological, and treatment-related variables were assessed. Descriptive and exploratory comparative analyses were performed between patients with and without ipsilateral recurrence. Results: A total of 417 lesions were analyzed, with 21 ipsilateral recurrences (5%) observed during follow-up. Among recurrent cases, 57% were non-invasive recurrent DCIS and 38% were invasive carcinomas. Most recurrences occurred in patients treated with breast-conserving surgery, and 52% of recurrent patients had not received adjuvant radiotherapy. All recurrent cases were estrogen receptor–positive at initial diagnosis, whereas none had received endocrine therapy. No clear association between recurrence patterns and tumor grade or tumor size emerged in this exploratory analysis. No distant metastases or disease-related deaths were observed during follow-up. Conclusions: Recurrence after treatment for pure DCIS was relatively uncommon and frequently non-invasive. Traditional clinicopathological variables alone appeared insufficient to consistently identify recurrence patterns in this cohort. These findings support the need for more individualized risk stratification approaches integrating clinical, imaging, and molecular factors in order to reduce potential overtreatment in selected patients with DCIS. Full article

To address the problems of blurred lesion boundaries, noise interference, and the lack of lightweight design in segmentation models for breast ultrasound images, this paper proposes a lightweight, high-real-time segmentation model, MV-UNet, based on Mamba architecture. The model employs an improved MambaVision encoder paired with a UNetMamba decoder. This architecture, augmented by a Local Supervision Module (LSM) during training, effectively integrates global context with local details while maintaining linear computational complexity, thereby enhancing boundary delineation capability. The experimental results on the BUSI_WHU dataset show that the MV-UNet achieves 90.51% in mIoU, 90.85% in Recall, and 4.59 pixels in ASSD, surpassing most of the existing advanced models in multiple metrics. At the same time, the number of parameters is only 14.7% of the EMGANet, and the inference speed is increased by 3.2 times. Furthermore, an independent benchmark test on the BUSI dataset demonstrates the model’s practical efficiency, achieving an ASSD of 14.94 pixels while maintaining its clear advantages in model lightness and inference speed. In summary, the excellent balance between segmentation accuracy and model efficiency achieved by MV-UNet provides a novel and effective approach for breast ultrasound image segmentation. Full article

Background/Objective: MicroRNA-21 (miR-21) is one of the most widely studied oncogenic microRNAs and has been implicated in breast cancer progression, therapy resistance, and metastatic potential. However, its utility as a long-term prognostic biomarker in patients undergoing mastectomy remains insufficiently clarified. This study evaluated the prognostic significance of miR-21 expression in predicting overall and disease-free survival. Methods: A retrospective cohort of 426 breast cancer patients who underwent mastectomy between 2010 and 2017 was analyzed. Tumor miR-21 expression was measured using quantitative real-time PCR and categorized as high or low based on cohort-derived thresholds. Long-term outcomes were assessed over a median follow-up of 112 months. Kaplan–Meier survival curves, log-rank tests, and multivariable Cox proportional hazards models were used to estimate associations between miR-21 levels and survival outcomes. Results: High miR-21 expression was identified in 48.8% of cases. Patients with high miR-21 demonstrated significantly poorer overall survival (10-year OS: 61.4% vs. 82.7%; log-rank p < 0.001) and disease-free survival (10-year DFS: 54.9% vs. 78.3%; log-rank p < 0.001). In multivariable analysis, high miR-21 remained an independent predictor of decreased OS (HR = 2.18; 95% CI: 1.56–3.04) and DFS (HR = 2.44; 95% CI: 1.78–3.33). Conclusions: Elevated miR-21 expression is a significant independent biomarker of adverse long-term prognosis in breast cancer patients undergoing mastectomy. Integrating miR-21 into postoperative risk stratification may improve individualized management strategies. Full article