Search Results (834)

Background/Objectives: Breast cancer is the most common malignancy among women globally, with survival rates improving due to earlier detection and better treatment. As a result, cancer survivors now constitute a growing segment of the population, and addressing their long-term health and well-being is a public health priority. Diet and nutrition represent modifiable factors that may influence recurrence, comorbidities, and quality of life (QoL), yet clear evidence-based guidance remains limited. This umbrella review thus synthesized evidence from published reviews on the effects of dietary and nutrition interventions among breast cancer survivors. Methods: Following a prospectively registered protocol in PROSPERO (CRD420251185022), six databases (PubMed, EMBASE, Scopus, Cochrane Library, PsycINFO and CINAHL) were systematically searched for systematic reviews/meta-analyses evaluating dietary or nutrition interventions in adult breast cancer survivors. Eligible reviews reported anthropometric, metabolic, psychosocial, or survival outcomes. Methodological quality was appraised using the AMSTAR-2 tool, and findings were narratively synthesized. Results: Nine systematic reviews encompassing more than 10,000 breast cancer survivors were included. Interventions ranged from general dietary counselling and structured weight-management programmes to Mediterranean-style dietary patterns, dietitian-led primary care, multiple health behaviour change interventions, mobile nutrition apps, and broader lifestyle programmes incorporating diet. Across reviews, interventions consistently improved diet quality and fruit–vegetable intake, produced modest but meaningful reductions in weight, body mass index, and body fat, and enhanced several QoL domains (e.g., fatigue, physical functioning, body image). Higher adherence to Mediterranean-style diets was associated with lower all-cause and non–breast cancer mortality, though certainty was limited by observational designs. However, evidence for long-term maintenance, survival endpoints, and ethnically diverse or low- and middle-income populations remains sparse. Conclusions: Dietary and nutrition interventions, particularly structured, dietitian-supported, and Mediterranean-style approaches, contribute to improved diet quality, sustainable weight control, and enhanced QoL among breast cancer survivors. Integrating nutrition care into survivorship pathways should be the focus of future research. Full article

Background: Socioeconomic disparities may drive cancer inequities in Hispanic/Latino populations. We examined associations of perceived access to healthy foods (AHF) and food insecurity (FI) with diet and body mass index (BMI) changes in Latina breast cancer (BC) survivors. Methods: Latina BC survivors in a 12-month intervention trial aiming to increase fruit/vegetable intake and physical activity were analyzed. AHF was from a modified, validated neighborhood environment scale and dichotomized (low–medium vs. high). FI was defined as eating less and/or going hungry due to a lack of money. AHF and FI surveys were self-reported. Outcomes included dietary intake, diet quality, and BMI. Fruit/vegetable intake was log-transformed. Relationships between AHF and FI and changes in diet and BMI were evaluated using generalized estimating equations. Results: Of women with AHF data (n = 86), 58% reported low–medium access and 42% reported high access. Fruit/vegetable (FV) intake declined overall from baseline to 12 months, with greater reductions among low–medium AHF women (−32%, 95% CI: −51%, −7%) compared with high AHF women (−17%, 95% CI: −40%, +13%). Statistically significant 12-month decreases in total calories, carbohydrates, sugars, and fat occurred in low–medium AHF women but not high AHF women, and changes in total energy density, carbohydrates, sugars, and BMI at 12 months were statistically significantly different between women with low–medium AHF and women with high AHF, p ≤ 0.05. Among 157 women, 23% reported FI. Reductions in fruit/vegetable intake were larger in women with FI (−39%, 95% CI: −57%, −14%) than in women without FI (−10% reductions, 95% CI: −25%, +8%) and between-group differences were significant at both 6 and 12 months, p ≤ 0.05. Most diet measures decreased for both FI and non-FI women, with greater decreases among those with FI. Conclusions: Latina BC survivors with FI or perceived limited AHF experienced greater declines in indicators of healthy diets including FV intake. Future interventions should integrate strategies to measure AHF and FI to address disparate access to healthy food options. Full article

Background: With the rising incidence of cancer, there is a growing need for improved preclinical models to test new therapies. While patient-derived xenografts (PDX) in immunodeficient mice are the gold standard, they are costly and result in a complete absence of a functional immune system, limiting their utility for studying tumor–immune interactions. This study characterizes a pharmacological partial immunosuppression protocol in immunocompetent mice as a promising alternative, evaluating its impact on the immune system and demonstrating its efficacy for growing human tumor xenografts. Methods: Mice received a regimen of cyclosporine (20 mg/kg, i.p., every 48 h for 12 days), cyclophosphamide (60 mg/kg, i.p., every 48 h for 8 days), and ketoconazole (10 mg/kg, p.o., for 12 days). The dynamics of CD3⁺, CD4⁺, CD8⁺, and CD19⁺ lymphocyte subpopulations and the CD4/CD8 index were monitored via flow cytometry on days 1, 5, 8, 12, 16, and 21. The protocol’s utility was tested by orthotopic transplantation of human glioma and lung cancer cells, and subcutaneous transplantation of breast cancer cells (MCF7). Tumor engraftment and growth were assessed using in vivo microscopy, MRI, and histology. Results: The immunosuppressive protocol induced a significant but partial reduction in CD3⁺ T-cells and CD19⁺ B-cells by day 8 (p = 0.0277). A profound and progressive decrease in the CD4/CD8 index was observed, indicating a shift towards immunosuppression. Crucially, CD8⁺ and CD4⁺ T-cells populations recovered rapidly post-therapy, demonstrating that the protocol creates a temporary and modifiable immune window rather than inducing complete ablation. The protocol enabled successful engraftment and growth of all three tested tumors in a residual immune microenvironment, confirmed by in vivo imaging and histopathological analysis. Conclusions: This drug-induced partial immunosuppression protocol effectively creates a reproducible state of transient immunodeficiency in outbred mice, suitable for various human tumor xenograft models. It represents a cost-effective and flexible alternative to genetic models, with the distinct advantage of preserving a residual immune microenvironment, making it particularly valuable for preclinical studies that require a partially intact host immune system. Full article

Background/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5–250 µM. IC₅₀ values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4–Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC₅₀ ± SD (µM)/SI: 4.3 ± 0.2/1.20 for A549, 6.4 ± 0.37/0.77 for MCF-7, 3.4 ± 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by ¹H-NMR, ¹³C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b–12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC₅₀ values in HeLa cells (10.6–13.6 µM) and high Selectivity Indexes (SI = 2.0–3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC₅₀ = 28.3–31.2 µM) with SI values ≥ 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b–12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b–12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC₅₀ values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization. Full article

Objective: Identifying biomarkers that predict metastatic potential or guide treatment selection is critical for improving breast cancer (BC) management. Previously, we established the Mitotic Network Activity Index (MNAI) as a prognostic marker in BC. Here, we bioinformatically and experimentally evaluated MNAI as a biomarker for metastasis risk and therapeutic response. Methods: We used Kaplan–Meier and Cox proportional hazard regression analyses to assess the association between MNAI and distant metastasis-free survival (DMFS) across 14 published BC datasets. A total of 16 publicly available clinical trial datasets, including the I-SPY trials, were used to evaluate the predictive value of MNAI for treatment response. Additionally, wound-healing and transmembrane assays were conducted to determine the effects of PLK1, CHEK1, and BUB1 inhibition on BC cell migration and invasion. Results: High MNAI levels were strongly associated with shorter DMFS. Multivariate analysis further confirmed MNAI as an independent risk factor for DMFS, beyond estrogen receptor status and PAM50-based molecular subtypes. Functionally, pharmacologic disruption of the mitotic network using PLK1, CHEK1, or BUB1 inhibitors significantly reduced cell migration and invasion in MDA-MB-231 and BT-549 BC cell lines. Moreover, BC cells with high MNAI increased sensitivity to microtubule-targeting agents such as docetaxel, paclitaxel, and ixabepilone but increased resistance to tamoxifen, AKT1/2 inhibitors, and mTOR inhibitors. Consistent with these findings, analysis of 16 clinical trial cohorts revealed that patients with high MNAI achieved higher pathological complete response rates to taxane-containing and ixabepilone-based therapies. Conclusions: Our findings demonstrate the MNAI as a clinically actionable biomarker that can refine risk stratification and guide the selection of targeted or chemotherapy regimens, advancing precision medicine in BC management. Full article

Background: Sleep disturbance (SD) is very common in breast cancer (BC) patients, resulting in poor therapeutic efficacy and prognosis. Diet may be associated with SD through systemic inflammation. This study aimed to evaluate the association between the energy-adjusted Dietary Inflammatory Index (E-DII) and SD, as well as the potential mediating role of inflammatory biomarkers in patients with BC. Methods: In this cross-sectional study, 302 BC patients were recruited, from whom 103 blood samples were obtained for the determination of plasma inflammatory biomarkers. Dietary intake was evaluated using 3-day, 24 h dietary recalls, while SD was assessed using the Pittsburgh Sleep Quality Index (PSQI). Results: SD was observed in 91 (30.13%) patients, who exhibited significantly higher E-DII scores, C-reactive protein (CRP), interleukins (IL-1β, IL-6, and IL-10), and tumor necrosis factor-α (TNF-α) levels compared to non-SD participants (p < 0.05). After adjusting for covariates, for every 1-point elevation in E-DII, the risk of SD increased by 23.0% (OR = 1.23; 95% CI: 1.04, 1.44; p = 0.014). Among the E-DII components, only vitamin C showed an inverse correlation with SD (OR = 0.99; 95% CI: 0.99, 1.00; p = 0.015). Mediation analysis showed that IL-1β, IL-10, IL-6, TNF-α, and CRP statistically mediated the association between E-DII and SD (all p < 0.05). The sensitivity parameters ρ were 0.3, 0.5, 0.4, 0.4, and 0.4, respectively. Conclusions: A diet with pro-inflammatory potential was correlated with SD among BC patients, which might be mediated by circulating IL-1β, IL-10, IL-6, TNF-α, and CRP. Full article

Background: Sentinel lymph node biopsy (SLNB) is the standard axillary staging procedure in clinically node-negative breast cancer but remains invasive, non-therapeutic and increasingly questioned in contemporary de-escalation algorithms. After neoadjuvant chemotherapy (NACT), however, the safety of omitting SLNB solely on the basis of a negative axillary ultrasound (AUS) is uncertain, particularly across molecular subtypes with heterogeneous chemosensitivity. This study evaluated the diagnostic performance of preoperative AUS after NACT and explored clinicopathological and biological factors associated with SLNB positivity in ultrasound-negative axillae. Methods: In this single-centre retrospective cohort, 135 women with invasive breast cancer who received NACT followed by surgery (2022–2024) were analysed. To avoid spectrum bias, 77 patients with clipped, cytologically or histologically proven node-positive disease at baseline were excluded from the main analysis. All patients underwent preoperative AUS and definitive axillary staging. Ninety-six women with ultrasound-negative axillae who proceeded to SLNB constituted the primary study population. Oestrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 and immunohistochemistry-based molecular subtype were recorded. Receiver operating characteristic (ROC) analysis and uni/multivariable logistic regression were used as exploratory tools to identify factors associated with SLNB positivity. Results: In the overall cohort, AUS sensitivity, specificity, negative predictive value and false-negative rate for axillary metastasis were 47.8%, 90.9%, 62.5% and 52.2%, respectively. Among ultrasound-negative axillae, SLNB was positive in 37.5%. Compared with SLNB-negative patients, those with SLNB metastases more frequently harboured an intratumoural ductal carcinoma in situ (DCIS) component, showed higher ER/PR expression and lower Ki-67, and were predominantly luminal A or luminal B/HER2−, whereas AUS performance appeared more favourable in HER2-enriched and triple-negative tumours. ROC-derived cut-offs for ER (82.5%), PR (25.0%) and Ki-67 (17.5%) provided only moderate discrimination (area under the curve 0.68–0.70). In multivariable analysis, absence of a DCIS component and low PR expression were independently associated with reduced odds of SLNB positivity, suggesting that DCIS and high PR may act as indicators of residual nodal risk in ultrasound-negative axillae. All estimates are limited by sample size and wide confidence intervals and should be interpreted as hypothesis-generating. Conclusions: Preoperative AUS alone cannot reliably exclude sentinel lymph node metastasis after NACT, particularly in luminal A and luminal B/HER2− tumours with strong hormone receptor expression and a low proliferative index. Until prospective, biology-stratified trials confirm the safety of omission, SLNB should not be withheld solely on the basis of a negative AUS in these subtypes. Axillary management after NACT should systematically integrate both imaging findings and tumour biology when considering further de-escalation of surgery. Full article

Background: Plant-based diets are recommended in guidelines for the prevention of cancer and cardiometabolic diseases, which remain major causes of death in breast cancer survivors (BCS). Since not all plant foods are healthy, we calculated the plant-based dietary index (PDI), healthy (hPDI) and unhealthy (uPDI), and their associations with cardiometabolic targets in BCS. Methods: Baseline dietary and cardiometabolic data were derived from 492 (median age 51, IQR 46–59) female BCS participating in a multicentric lifestyle trial conducted in Italy. Dietary data were collected with 7-day food records. PDI, hPDI, and uPDI were calculated by assigning positive scores to all plant foods, healthy plant foods or less healthy plant foods, respectively, as defined by the literature (scores ranged from 18 to 90). Using logistic or multinomial regression models, we estimated the odds ratios (OR) and the corresponding 95% confidence intervals (CI) between PDIs and cardiometabolic risk factors. Results: The OR of being obese (BMI ≥ 30 Kg/m²) was 0.47 (95%CI: 0.29–0.77), 0.37 (95%CI: 0.22–0.61) and 1.38 (95%CI: 0.83–2.28) with higher PDI, hPDI and uPDI, respectively. The OR of having a large waist circumference (≥88 cm) was 0.64 (95%CI: 0.42–1.00) with higher hPDI. The OR for hypercholesterolemia (≥200 mg/dL) was 1.80 (95%CI: 1.16–2.78) with higher uPDI. The ORs of hypertriglyceridemia (≥150 mg/dL) and metabolic syndrome were 0.38 (95%CI: 0.20–0.71) and 0.59 (95%CI: 0.35–0.97), respectively, with higher PDI. No other significant association was observed. Conclusions: Maintaining cardiometabolic risk factors within normal ranges is clinically relevant in BCS, and this may be more likely when a plant-based diet is consumed, especially if low in unhealthy plant foods. Full article

Background/Objectives: Breast cancer is the leading cause of cancer-related mortality in women, highlighting the urgent need for robust prognostic tools to enable individualized risk stratification. Methods: Transcriptomic data from 1075 breast cancer and 113 adjacent normal tissues in The Cancer Genome Atlas (TCGA) were integrated with clinical information. Differential expression analysis identified 531 immune-related genes, which were further selected by univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression to construct a 13-gene prognostic signature. The model was validated in an independent cohort (n = 327). Tumor immune microenvironment and single-cell RNA sequencing data were analyzed to explore underlying biological differences. Results: The 13-gene signature effectively stratified patients into low- and high-risk groups with significantly different overall survival in both the TCGA cohort (log-rank p < 0.0001; C-index = 0.678; 5-year AUC = 0.72) and the validation cohort (log-rank p < 0.0001; C-index = 0.703; 3-year AUC = 0.81). Low-risk tumors exhibited an antitumor immune microenvironment enriched in CD8⁺ T cells, T follicular helper (Tfh) cells, and M1 macrophages, whereas high-risk tumors were dominated by immunosuppressive regulatory T cells and M2 macrophages (all p < 0.0001). Single-cell analysis revealed expansion of malignant epithelial cells and inflammatory cancer-associated fibroblasts (iCAFs) in high-risk tumors, with higher iCAF scores significantly associated with poorer survival (log-rank p = 0.00036). Conclusions: Collectively, this study delivers a rigorously validated 13-gene immune signature whose prognostic utility is rooted in distinct immune microenvironmental features, while unveiling iCAF-targeted therapeutic strategies as a promising intervention avenue. Full article

This study addresses the limited mechanistic understanding behind medical imaging for tumor microenvironment (TME) assessment. We developed a novel framework that analyzes tumor imaging heterogeneity index (TIHI)-correlated genes to uncover underlying TME biology and therapeutic vulnerabilities. DCE-MRI and mRNA data from 987 high-risk breast cancer patients in the I-SPY2 trial, together with mRNA data from 508 patients in GSE25066, were analyzed. TIHI-associated genes were identified via Pearson correlation, clustered via weighted gene co-expression network analysis (WGCNA), and subgroups were defined via non-negative matrix factorization (NMF). The clinical relevance of the image-to-gene comprehensive (I2G-C) subtype defined by subgroups was assessed using logistic regression and Cox analysis. I2G-C comprised four clusters with distinct immune and replication/repair functions. It further stratified receptor, PAM50, and RPS5 subtypes. The “immune+/replication+” was more likely to achieve pathological complete response (pCR) (OR = 2.587, p < 0.001), while the “immune−/replication−” was the least likely to achieve pCR (OR = 0.402, p < 0.001). The “immune+/replication+” showed sensitivity to pembrolizumab (OR = 10.192, p < 0.001) and veliparib/carboplatin (OR = 5.184, p = 0.006), while “immune-/replication-” responded poorly to pembrolizumab (OR = 0.086, p < 0.001). Additionally, “immune+/replication-” had the best distant recurrence-free survival (DRFS), whereas “immune-/replication+” had the worst (log-rank p = 6 × 10⁻⁴, HR = 5.45). By linking imaging heterogeneity directly to molecular subtypes and therapeutic response, this framework provides a robust, non-invasive surrogate for genomic profiling and a strategic tool for personalized neoadjuvant therapy selection. Full article

Background/Objectives: Large language models (LLMs) have been proposed as a means of converting unstructured electronic medical records (EMRs) into structured datasets. However, concerns regarding the reliability of these models in non-English clinical text and their capacity to generate novel insights remain unresolved. We aimed to utilize an LLM to identify a hypothetical “Luminal B poor-prognosis” breast cancer subgroup (LPP) based on progesterone receptor (PR), the Ki-67 proliferation index, and grade characteristics, while concurrently validating the LLM’s accuracy. Methods: We retrospectively compiled the EMRs on 7756 female breast cancer patients from five Moscow oncology centers. An LLM with a domain-engineered prompt extracted eight clinicopathological variables (Ki-67, estrogen receptor (ER)/PR Allred status, HER2 status, grade, relapse dates, and multiple primaries). The accuracy of the model was validated in 366 randomly sampled cases against oncologist annotations using Intraclass Correlation Coefficient (ICC) and weighted κ. Following data post-processing, the complete-case cohort (n = 2347) and the HR+/HER2− stage I–III sub-cohort (n = 1419) were analyzed. Survival was estimated with Kaplan–Meier/log-rank and modeled with Cox regression (adjusted for age, stage, and treatment). Ki-67 was modeled continuously; prespecified LPP definitions were compared. Results: LLM–human agreement was high (Ki-67 ICC = 0.882; grade κ = 0.887; ER κ = 0.997; PR κ = 0.975; HER2 κ = 0.935). Date extraction was characterized by a high degree of missing data. In HR+/HER2− stage I–III disease, ER < 5 was non-prognostic; however, PR < 4 and Ki-67 ≥ 40% were indicative of inferior survival (HR 2.25 and 1.85). The most effective LPP definition (PR < 4 and Ki-67 ≥ 40%) identified a subgroup (~5.3%) of patients with markedly poorer outcomes (age, stage, and treatment adjusted HR 2.60, 95% CI 1.53–4.43) compared to the Luminal B (HER2−) subgroup. Conclusions: The developed LLM has demonstrated the ability to reliably structure non-English EMRs and enable discovery of clinically meaningful subgroups. The discovered LPP phenotype defines a small, high-risk subset warranting external validation. Given the retrospective, single-system design of the study, it is imperative to interpret the discovered phenotype features as hypothesis-generating, rather than as definitive evidence. Full article

Background/Objectives: Therapeutic resistance remains a major obstacle in breast cancer management, particularly among estrogen receptor-positive (ERα⁺) tumors that initially respond to endocrine therapy such as tamoxifen. Type XI collagen (COL11A1), a minor fibrillar collagen secreted by cancer-associated fibroblasts, has recently emerged as a stromal biomarker linked to tumor progression, immune modulation, and poor prognosis in several solid malignancies. Methods: We conducted a narrative review of the literature indexed in PubMed, Scopus, and Web of Science between 2011 and 2025, including original research, reviews, and clinical studies addressing COL11A1 expression and function in breast cancer. Mechanistic studies in other cancer types (ovarian, pancreatic, lung) were also evaluated when relevant to breast cancer biology. Results: Across multiple cancer types, COL11A1 overexpression correlates with stromal remodeling, epithelial–mesenchymal transition, and resistance to both hormone therapy and chemotherapy. In breast cancer, emerging data suggest a potential prognostic role and possible involvement in shaping the immune microenvironment. Nevertheless, most evidence derives from retrospective or preclinical studies, and clinical validation remains limited. Conclusions: COL11A1 represents a promising, though still exploratory, biomarker of therapeutic resistance and immune modulation in breast cancer. Future prospective and subtype-specific studies are needed to clarify its diagnostic and therapeutic value and to determine whether its inclusion in immunohistochemical panels could enhance patient stratification and guide personalized treatment. Full article

Background: Postoperative radiation therapy (RT) after lumpectomy reduces the risk of locoregional recurrence in ductal carcinoma in situ (DCIS). However, the potential association between RT and ischemic heart disease (IHD) remains uncertain. This nationwide cohort study evaluated the long-term impact of postoperative RT on IHD risk and overall survival (OS) in women with DCIS using real-world data from the Korean National Health Insurance Service (NHIS). Methods: Women diagnosed with DCIS who underwent breast-conserving surgery between 2003 and 2020 were identified from the NHIS claims database. Patients with invasive breast cancer, age under 20 years, a prior history of IHD, or missing smoking or body mass index (BMI) data were excluded. Multivariable Cox regression was performed to assess the association between postoperative RT, IHD incidence, and OS, adjusting for key cardiovascular risk factors. Results: Among 4633 eligible patients (RT, 2778; no RT, 1855), the median follow-up duration was 86.1 months, and baseline characteristics were well balanced between groups without major differences in cardiovascular risk factors. A total of 126 patients (3.4%) developed IHD, with a 10-year cumulative incidence of 4.7%. Older age, hypertension, and hyperlipidemia were independent risk factors for IHD, whereas postoperative RT was not significantly associated with increased IHD risk (hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.77–1.48; p = 0.690). The 10-year OS rate was 98.0%, and postoperative RT remained an independent predictor of improved survival (HR = 0.47, 95% CI = 0.28–0.79; p = 0.004). Conclusions: Postoperative RT did not increase the long-term risk of IHD but was associated with improved OS in patients with DCIS. These findings provide population-based evidence supporting the cardiac safety and oncologic efficacy of postoperative RT, while recognizing that unmeasured differences in health behavior or medical care utilization could have contributed to the observed survival benefit. Full article

Triple-negative breast cancer (TNBC) is known for being aggressive and potentially resistant to chemotherapy. This means that new ways to improve cancer treatments are a priority. So, the anticancer effect of binary combinations of fucoidan (FuLt) and the chemotherapeutic agents doxorubicin, paclitaxel, and 5-fluorouracil was evaluated. The Chou-Talalay combination index method was used to do this. This method allows the assessment of interactions between products by determining synergism, additive effect and antagonism with combination index <1, =1 and >1, respectively. Synergistic indices (SIs) were selected and applied to 4T1 homotypic spheroids. Oxidative stress caused by SIs was determined after 72 h by measuring the production of ROS and NO in both homotypic and heterotypic spheroids. Three SIs with an inhibitory effect of at least ≥ 0.50 and a dose reduction index > 1 were selected. Considering the experimental and simulated SI, twelve, nineteen, and seven SIs were found for FuLt with doxorubicin, paclitaxel, and 5-fluorouracil, respectively. The highest levels of ROS and NO occurred at 12 and 72 h, respectively, in homotypic and heterotypic spheroids, indicating an immunomodulatory effect in heterotypic spheroids. These results suggest that the synergistic combination of FuLt with chemotherapeutic agents improves drug efficacy and modulates redox dynamics in 4T1 spheroids. Furthermore, FuLt alone exhibits cytotoxic properties. Full article

The immune control of cancer growth is an area of active investigation. In this study, we demonstrated the feasibility of using standard immunohistochemistry methods in conjunction with a set of newly developed chromogens to demonstrate immune cell markers in a multiplex staining system. Immune infiltrating cells in breast cancer were identified using antibodies to CD20 (B-cells), CD3 (T-cells), and CD163 (macrophages). Additionally, the tumor compartment was identified using cytokeratin (AE1/AE3), and Ki67 was used to determine the proliferation index. These stains showed a significant immune cell infiltrate surrounding and within the tumors. B-cells, T-cells, and macrophages were abundant at the tumor periphery, particularly in areas where tertiary lymphoid structures were also present. In contrast, B-cells were significantly reduced within the tumor interior compared to an abundant infiltrate of T-cells and macrophages. Patterns of B-cell, T-cell, and macrophage infiltration were identified. Depending upon the particular set of markers chosen for analysis, a simple visual examination, without the aid of computer-assisted imaging systems, was sufficient to differentiate up to five different markers. Full article