MAL/SPP1 axis drives tumor proliferation and immune evasion via JAK2/STAT3 and MHC class Ib in breast cancer.

The association between breast cancer diagnosis and treatment and the risk of incident ischemic stroke remains unclear. We investigated ischemic stroke risk among breast cancer survivors and evaluated associations by age, follow-up duration, and type of cancer treatment. We conducted a nationwide, retrospective, matched cohort study using the Korean National Health Insurance Service database. Women aged 18 years and older with newly diagnosed breast cancer who underwent breast cancer surgery between January 2010 and December 2016 and had no prior stroke were identified. Each was matched 1:3 by birth year to cancer-free women. The primary outcome was first ischemic stroke, defined as hospitalization with International Classification of Disease, Tenth Revision codes I63/I64 plus inpatient brain CT or MRI. Subdistribution hazard ratios (sHRs) and 95% CIs were estimated using Fine-Gray models that accounted for death as a competing risk and adjusted for sociodemographic factors and cardiovascular and non-CV comorbidities. We analyzed 107,606 breast cancer surgery survivors (mean age, 50.0 years) and 322,818 matched cancer-free women. Over a mean 7.2-year follow-up, ischemic stroke occurred in 1,155 survivors (1.07%). Stroke risk was elevated shortly after breast cancer diagnosis (1-year sHR 1.59; 95% CI 1.34-1.89; 3-year sHR 1.17; 95% CI 1.05-1.30) compared with cancer-free women, with stronger associations at 3 and 6 months after diagnosis across all age groups. Over the long term, survivors had a slightly lower risk of stroke (sHR 0.94; 95% CI 0.88-1.00), and in a 1-year landmark analysis including only event-free individuals, the risk was lower (sHR 0.87, 95% CI 0.81-0.93). Among survivors, anthracycline use (sHR 1.25) and combined tamoxifen-aromatase inhibitor therapy (sHR 1.49) were associated with increased risk of stroke, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations attenuated and became nonsignificant beyond 1 year. Stroke risk was also higher among survivors with low income, hypertension, diabetes, or current smoking. The association between breast cancer and ischemic stroke risk is time dependent, with a short-term increase after diagnosis and treatment followed by a gradual decline over time. These findings highlight the need for proactive stroke risk management, including early CV assessment and ongoing monitoring for thromboembolic events during survivorship.

Imaging-guided photodynamic control of autophagy-apoptosis switching in breast cancer using hypericin-functionalized upconverting nanoparticles.

The present review examines the intricate relationship between icariin and breast cancer (BC), encompassing foundational theoretical concepts, epidemiological data, diagnostic methodologies, therapeutic approaches, ongoing debates and prospective future developments. The foundational theoretical concepts address the mechanisms through which icariin influences BC pathogenesis, as well as its pharmacokinetic and pharmacodynamic properties and historical context. The epidemiological section analyzes the global incidence and prevalence of BC, alongside its underlying pathophysiology. Diagnostic methodologies are discussed with a focus on imaging technologies, biomarkers, and the innovative role of icariin in advancing diagnostic techniques. Therapeutic approaches investigate icariin's potential as a chemo-preventive agent, its synergistic interactions with conventional therapies and the outcomes of clinical trials. The section on controversies explores discussions surrounding icariin's efficacy, safety and the associated regulatory and ethical considerations. Future directions emphasize emerging trends, the potential for personalized medicine, and future prospects in BC treatment. The present review aims to offer a comprehensive understanding of icariin's role in BC research and therapeutic applications.

AGO Breast Committee recommendations for the surgical therapy of breast cancer: Working Group on Gynecologic Cancers (AGO) update 2026.

Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly advanced the treatment of hormone receptor-positive, HER2-negative metastatic breast cancer, improving outcomes. However, their concurrent use with statins, a widely prescribed class of drugs, may pose a risk of rhabdomyolysis due to pharmacokinetic and pharmacodynamic interactions. This systematic review analyzes reported cases to characterize clinical presentations, therapeutic approaches, and outcomes. A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to January 2026 for case reports and case series documenting rhabdomyolysis in patients treated with CDK4/6 inhibitors. Data on demographics, clinical features, laboratory findings, management strategies, and outcomes were extracted. Quality assessment of the included cases was performed using the Joanna Briggs Institute Critical Appraisal Checklist. Seven case reports involving female patients aged 55-81 years were analyzed. All patients were treated for metastatic breast cancer with CDK4/6 inhibitors (ribociclib, palbociclib, or abemaciclib) alongside statins (simvastatin, atorvastatin, or rosuvastatin). Rhabdomyolysis onset ranged from 3 days to 48 months after initiation of combination therapy, or shortly after statin dose escalation in the setting of long-term CDK4/6 inhibitor use. Clinical presentations included severe myalgia, muscle weakness, and dark urine, with creatine kinase levels ranging from 3,070 to 47,000 U/L. Acute kidney injury was reported in five cases. Management primarily involved cessation of the implicated drugs and aggressive hydration, with adjunctive treatments such as corticosteroids, plasma exchange, or intravenous immunoglobulin. Five patients recovered fully, one had partial recovery with persistent renal dysfunction, and one fatality was reported. Rhabdomyolysis due to CDK4/6 inhibitor-statin interactions is a rare but potentially life-threatening complication. Vigilant monitoring, timely intervention, and tailored treatment strategies are essential for preventing complications and improving patient outcomes.

This study aimed to evaluate the efficacy of the lymphatic microsurgical preventive healing approach (LYMPHA) in preventing lymphedema after axillary lymph node dissection (ALND) for breast cancer. This retrospective, single-center study analyzed 550 women who underwent axillary lymph node dissection (ALND) between January 2008 and July 2009. The analysis included 500 patients who completed long-term follow-up evaluation. The patients were divided into two groups: 270 patients who underwent ALND with LYMPHA, including 203 who also received radiotherapy and 230 patients who underwent ALND without preventive microsurgical treatment, 173 of whom received radiotherapy. The LYMPHA procedure consisted of performing lymphatic-venous anastomoses at the time of ALND. All the patients were followed up for as long as 15 years with arm volumetry and lymphscanner measurements. Arm lymphedema developed in 5 (2.5 %) of the 203 patients who underwent ALND with LYMPHA plus radiotherapy and in 1 (1.5 %) of the 67 patients who underwent ALND with LYMPHA alone. In the group without LYMPHA, lymphedema occurred in 78 (45 %) of the 173 patients who underwent ALND with radiotherapy and in 17 (30 %) of the 57 patients who underwent ALND without radiotherapy. Lymphedema onset occurred 6 to 36 months after surgery. The lymphedema-free cumulative probability was significantly higher in the LYMPHA group than in the no-LYMPHA group (0.978 vs 0.587; p < 0.001). In addition, changes in arm volume relative to baseline at 15 years were significantly lower in the LYMPHA group (p < 0.01). For the primary prevention of secondary arm lymphedema, LYMPHA is an effective technique.

Learning to breathe for radiation therapy: A scoping review of deep inspiration breath-hold training.

Breast cancer treatment is rapidly evolving toward precision-based de-escalation strategies for oncological safety and minimizing treatment-related morbidity. In early stage disease, minimally invasive approaches, such as non-surgical ablation techniques, including cryoablation and radiofrequency ablation, potentially constitute alternatives to conventional surgery for carefully selected low-risk tumors. Active surveillance trials challenge the necessity of immediate surgery for low-risk ductal carcinoma in situ, reflecting a paradigm shift toward risk-adapted management. In the neoadjuvant setting, achieving radiologic and pathologic complete responses, particularly in HER2-positive and triple-negative subtypes, is being investigated to determine the feasibility of omitting breast surgery under strict imaging and biopsy-guided protocols. Circulating tumor DNA-based minimal residual disease assays offer a promising tool for refining risk stratification and potentially guiding the extent of surgery and adjuvant therapy. These strategies represent a transformative movement toward biologically tailored, response-adapted, less invasive treatments for early breast cancer to optimize quality of life without compromising long-term outcomes.

Breast cancer is the most common cancer diagnosed globally, with various levels of heterogeneity. The current treatment strategy for breast cancer includes surgery, chemotherapy, radiation, hormone, targeted, and immunotherapy. These strategies are combined according to the stage, patient factors, and molecular subtype of breast cancer to enhance survival and diminish the recurrence of cases. Several adverse effects and challenges are associated with these therapies, which render the patient uncomfortable and non-compliant. Bioconjugate-based therapy is one of the advanced therapies emerging to diagnose and treat breast cancer, in which conjugation is done between various molecules, such as monoclonal antibodies and cytotoxic drugs, radionuclides, enzymes, polymers, ligands, and nanoparticles, using linkers. This review aims to critically discuss bioconjugate's recent research advancements in breast cancer theranostics, highlighting their strengths and gaps toward clinical translation, along with patents and clinical trials. PubMed, Scopus, and Google Scholar were used to search the literature in the last five years (2021 to present). The outcomes of the findings are promising; however, more studies need to be done to establish the mechanistic pathway, long-term toxicity, safety, efficacy, and stability of the bioconjugates for breast cancer to move toward clinical settings.

Deep learning approaches for predicting Ki-67 index in breast cancer histopathology images: A systematic review.

To investigate MRI-based breast edema patterns as biomarkers of tumor aggressiveness and their predictive value for pathological response to neoadjuvant chemotherapy (NAC) in invasive breast cancer. This retrospective study evaluated 235 female patients (mean age, 52 ± 12 years) with biopsy-proven invasive breast cancer who underwent pre-NAC breast MRI. After excluding 19 patients (10 for inadequate image quality, 9 for post-biopsy imaging), 216 patients were analyzed. Breast edema score (BES) was independently assessed by two radiology residents to evaluate interobserver agreement. Subsequently, a breast radiologist reviewed all cases to establish the definitive dataset. The differences in clinicopathological characteristics between the two groups and between different BES were compared. Interobserver agreement for BES classification was very high (92.6% concordance). Edema presence correlated significantly with larger tumor size (p = 0.001), higher histological grade (p = 0.001), axillary lymph node metastasis (p = 0.015), hormone receptor negativity (p < 0.001), lymphovascular invasion (p = 0.031), and elevated Ki-67 (p = 0.001). Higher BES groups (BES 2-4) showed stronger associations with aggressive features: tumor size (p < 0.001), grade (p = 0.022), hormone receptor negativity (p = 0.001), non-luminal subtypes (p = 0.001), and intratumoral necrosis (p = 0.002). Neither edema nor BES predicted pathological response to NAC (p = 0.999, p = 0.299). BES and edema are robust imaging biomarkers of tumor aggressiveness but demonstrate no predictive value for NAC response. MRI-based edema scoring holds clinical relevance for noninvasive tumor phenotyping and risk stratification in breast cancer management. Question Can MRI-based breast edema patterns predict tumor aggressiveness and pathological response to neoadjuvant chemotherapy in invasive breast cancer patients, aiding noninvasive risk stratification? Findings BES correlates with aggressive tumor features (larger size, higher grade, hormone negativity; all p < 0.050 but shows no predictive value for NAC response (p = 0.299). Clinical relevance BES serves as a practical imaging biomarker for risk stratification and tumor phenotyping, guiding individualized therapy. However, it shows no utility in predicting NAC response, emphasizing the need for complementary predictive tools in treatment planning.

Engineering biodegradable lipid nanoparticles with endo-lysosomal escape capability for chronological therapeutic immunomodulation to enhance interleukin-15 therapy.

Introduction: Breast cancer is the most frequently encountered malignant tumour in women around the world with high incidence and mortality rates worldwide. The concept of being able to prognosticate breast cancer based on routine peripheral blood examinations is attractive given the ease of access, replicability, and lower cost. Aim: To estimate the Systemic Immune-inflammatory Index (SII) and Systemic Inflammatory Response Index (SIRI) in invasive ductal carcinoma of breast and to study association between SII and SIRI with prognostic parameters such as molecular subtypes, Grade and Stage of the disease. Materials and Methods: This retrospective cross-sectional analytical study was conducted at Departments of Pathology and Surgical Oncology, Sri Devaraj Urs Medical college, Tamaka, Karnataka, India, from February 2024 to August 2024 it included 90 histopathologically confirmed cases of invasive ductal carcinoma of the breast diagnosed between January 2018 and December 2020. Clinicopathological data such as age, tumour grade, stage, and molecular subtype were obtained from medical records. Neutrophil, lymphocyte, monocyte, and platelet counts were obtained from case files. The SII and SIRI were calculated using standard formulas. Optimal cut-off values were derived using Receiver Operating Characteristic (ROC) curve analysis, and patients were categorised into high and low index groups. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) version 22.0. Associations between inflammatory indices and prognostic parameters were assessed using the Chi-square test, with p&lt;0.05 considered statistically significant. Results: A total of 90 patients with invasive ductal carcinoma of the breast were included in the study. Based on ROC analysis, the cut-off values for SII and SIRI were 568.83 and 0.831, respectively. High SII levels showed a statistically significant association with histological grade (p=0.002). However, no significant association was observed between SII and tumour stage (p=0.235) or molecular subtype (p=0.770). Similarly, elevated SIRI levels were significantly associated with histological grade (p=0.013) and tumour stage (p=0.022). No significant association was observed between SIRI and molecular subtypes (p=0.734). Conclusion: Systemic inflammatory indices such as the SII and SIRI represent accessible, inexpensive, and non invasive tools that may aid in prognostic assessment and risk stratification in patients with invasive ductal carcinoma of the breast. Their evaluation using routine peripheral blood parameters highlights the potential clinical utility of inflammation-based biomarkers in the overall management and prognostication of breast cancer.

Trastuzumab deruxtecan (T-DXd) has recently reshaped the management of HER2-low metastatic breast cancer. While pivotal trials relied on CT-based RECIST 1.1, [18F]FDG PET/CT provides high diagnostic sensitivity and valuable semi-quantitative metrics, though its role in monitoring antibody-drug conjugates remains insufficiently defined. This study assessed the prognostic value of PET-derived parameters and PERCIST criteria in patients treated with T-DXd. This retrospective study included all HER2-low metastatic breast cancer patients treated with T-DXd between 2022 and 2025 at the Strasbourg Europe Cancer Institute (ICANS) who underwent [18F]FDG PET/CT. Semi-quantitative parameters (SUVmax, SULpeak) and metabolic response according to PERCIST 1.0 were collected. Their association with overall survival (OS), metabolic progression-free survival (mPFS) and time-to-treatment change (TTT) was analyzed using Cox models and Kaplan-Meier curves. Forty-three patients were included. Baseline SULpeak of the most hypermetabolic lesion was an independent prognostic factor for OS, mPFS and TTT (p < 0.05). A ROC-derived cutoff of 6 identified two prognostic groups, with SULpeak < 6 associated with significantly improved outcomes. Early metabolic response was also linked to longer OS and PFS (p< 0.05), with median PFS of 9.2 vs. 4.2 months (HR 2.67; 95% CI 1.30-5.47). Combining baseline SULpeak and metabolic response (complete or partial metabolic response) defined three risk groups with significantly different OS and PFS. [18F]FDG PET/CT provides significant prognostic information in HER2-low metastatic breast cancer treated with T-DXd. Baseline SULpeak and early PERCIST response enable meaningful risk stratification. The proposed prognostic model requires prospective validation before clinical implementation.

Axillary management in early-stage breast cancer is increasingly shifting toward de-escalation. While sentinel lymph node biopsy (SLNB) remains standard, evidence suggests axillary ultrasound (AUS) may safely replace SLNB in selected patients. The SOUND trial demonstrated noninferior oncologic outcomes with AUS-based staging among clinically node-negative patients with small (≤ 2 cm), unifocal invasive breast cancers and negative preoperative AUS. However, the economic and health system impact of implementing this strategy in routine practice remains unclear. We conducted a retrospective cohort analysis of 221 SOUND-eligible patients who underwent breast-conserving surgery with SLNB at four affiliated hospitals between January and June 2023. Costs were modeled using 2025 Medicare reimbursement rates, comparing the observed SLNB pathway with a theoretical AUS-only approach. Estimates included procedural, anesthesia, pathology, and complication-related costs, analyzed from both hospital and patient perspectives. Total estimated hospital costs were $1192,159.56 for SLNB versus $111,825.65 for AUS-only staging, a 90.6% reduction. Mean patient out-of-pocket costs decreased similarly (from $1078.88 to $101.20 per patient). SLNB added an average of 15.1 min of operative time and increased pathology workload owing to lymph node processing. In SOUND-eligible patients, axillary staging with ultrasound alone provides substantial reductions in cost, operative time, and resource utilization while supporting a less invasive, value-based approach to breast cancer care. Together with existing evidence, these findings support broader implementation of the SOUND strategy in appropriately selected populations, particularly postmenopausal patients over 50 years undergoing breast-conserving surgery for cT1N0, ER-positive, HER2-negative invasive ductal carcinoma with a negative AUS.

Postoperative regional nodal irradiation (RNI) is a standard treatment for breast cancer at high risk of regional recurrence; however, the necessity of including the internal mammary node (IMN) region in the radiation field remains unclear. This study aimed to evaluate treatment outcomes in a large cohort of patients who received postoperative radiotherapy with RNI excluding the IMN region. This study included patients with breast cancer who underwent surgery followed by RNI without IMN irradiation between 2007 and 2018. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS), breast cancer-specific mortality (BCM), distant metastasis-free survival (DMFS), recurrence patterns, and treatment-related adverse events. In total, 799 patients were included. The 5-year DFS, OS, BCM, and DMFS rates were 75.9, 88.3, 9.7, and 77.1%, respectively. Worse outcomes were associated with a higher number of positive lymph nodes and estrogen receptor (ER)-negative disease. Medial/central tumor location and younger age were each significantly associated with poorer outcomes, being associated with worse DFS and DMFS. Bone was the most common recurrence site. ER-negative disease, a higher number of positive lymph nodes, medial/central location, and younger age were significant risk factors for recurrence, particularly distant metastasis. IMN recurrence was rare. In this cohort, medial/central tumor location, ER-negative disease, and extensive nodal involvement were associated with poorer outcomes, suggesting that these factors may identify patients who can benefit from IMN irradiation. These findings may serve as important reference data when determining the indication for IMN irradiation on an individual patient basis.

Sertraline-loaded targeted nanocarrier for breast cancer treatment: in vitro and in vivo assessment

Tongguanteng injection induces cell cycle arrest and drives ferroptosis through AURKA/KEAP1/NRF2 axis in breast cancer.

Integrating multi-omics and artificial intelligence for personalized breast cancer management: A guide to clinicians.