Breast cancer research papers

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Health and productivity benefits of anti-PD-(L)1 agents for early-stage cancer treatment in Hungary. reports: Anti-PD-(L)1 agents, inhibitors of programmed cell death protein 1 (PD-1) or its ligand (PD-L1), are established therapies that improve cancer management as well as the disease and societal burden of specific metastatic and early-stage cancers. The aim of the study was to determine the impact of adopting anti-PD-(L)1 agents for the treatment of all eligible patients with early-stage cancers versus reserving anti-PD-(L)1 agents for patients with metastatic disease alone in Hungary. This study evaluated two scenarios, one where anti-PD-(L)1 agents were used to treat all eligible early-stage disease case s (ESD scenario) of melanoma (stage IIB-C and III), renal cell carcinoma (RCC), and triple-negative breast cancer (TNBC) versus a reference scenario where anti-PD-(L)1 agents were only used to treat metastatic disease cases in Hungary (2024-2033).

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Digital spatial profiling of α-PD-1 treated breast cancer bone metastases reveals region-specific signaling and enrichment of immune-suppressive markers. reports: Bone is the most common and preferential site for breast cancer metastasis. Upon dissemination to the bone, breast cancer cells engraft into multiple niches, but it is unclear whether there are region-specific differences that may drive breast cancer progression in bone. We used a proteomic digital spatial profiling (DSP) approach to investigate which proliferation, cell death, and immune-related markers and pathways are enriched in immune and cancer cells residing 1) in the bone marrow or 2) along the endosteal surface, in an E0771, α-PD-1 treated pre-clinical model of breast cancer bone metastasis.

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Living bacterial reactor potently activates tumor immunogenic ferroptosis via cysteine depletion and photothermal therapy. reports: Bacterial combination therapy offers immense promise for treating aggressive "cold" solid tumors, such as triple-negative breast cancer (TNBC). However, the clinical translatability of traditional genetic engineering is often hampered by operational complexity and genetic instability. Here, we developed A-SPB-a non-genetically engineered, multi-functional living bioreactor based on Shewanella oneidensis MR-1 (SO), surface-modified with Prussian blue (PB) nanoparticles and attenuated via deoxycholic acid (DA) treatment.

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Ultrasound-triggered carrier-free nanoprodrugs activate cGAS-STING pathway to enhance tumor-targeting chemo-immunotherapy. reports: Chemotherapy-induced cell apoptosis results in nuclear damage and the subsequent release of double-stranded DNA (dsDNA) fragments, which can stimulate the cGAS-STING pathway to initiate antitumor immune responses. However, this pathway may be less effective due to nonspecific systemic toxicity caused by chemotherapeutic agents and inefficient dsDNA accumulation. This study aimed to develop an ultrasound (US)-triggered carrier-free nanoprodrug PBSN38-curcumin (PBSN38-CUR), incorporating the sonosensitizer curcumin (CUR) and reactive oxygen species (ROS)-responsive prodrug pinacol boronic ester-conjugated 7-ethyl-10-hydroxycamptothecin (PBSN38).

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An AIB1 isoform rewires glucocorticoid receptor signaling to promote TNBC progression. reports: The role of glucocorticoid receptor (GR) signaling in triple-negative breast cancer (TNBC) progression remains poorly defined. Here, we describe a GR-dependent mechanism driving TNBC invasion, mediated by the presence of a subpopulation of cancer cells that express an N-terminal truncated splice isoform of the nuclear receptor coactivator AIB1. Invasion was driven through direct contact of this subpopulation with neighboring cancer cells, and suppressed by GR antagonists or depletion of GR.

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Does Multidisciplinary Clinic Impact Rates of Breast Conserving Therapy? reports: Previous studies have identified factors associated with higher rates of breast conservation therapy (BCT), but the impact of multidisciplinary clinic (MDC) has not been documented. We hypothesized that patients who underwent MDC consultation with both surgical and radiation oncologists would have increased BCT rates compared with patients seeing providers separately. A retrospective chart review was conducted in patients diagnosed with stage 0-III breast cancer in 2023 who were offered BCT.

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Effect of carbamazepine on the pharmacokinetics of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader, in healthy adults. reports: To evaluate the effects of carbamazepine, a strong cytochrome P450 (CYP)3A4 inducer, on the pharmacokinetics and safety of vepdegestrant, a PROteolysis TArgeting Chimera estrogen receptor degrader. This was a phase 1, open-label, fixed-sequence, two-period study in healthy adult participants. During Period 1, a single oral dose of vepdegestrant 200 mg was administered (Day 1).

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Exon 7 splicing of ERα predicts poor prognosis and increases phenotypic heterogeneity in luminal a subtype breast cancer. reports: ERαΔ7 is one of the most frequently observed splice variants of the ESR1 gene in breast cancer but its functions remain largely unknown. Here we report that ERαΔ7 predicted poor survival in luminal A type breast cancer from TCGA data. ERαΔ7 occurred more frequently in luminal type breast cancer, with expression inversely correlating with ESR1 expression.

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GPX4 Inhibitor Resistance and Metastatic Features in Triple-Negative Breast Cancer. reports: Leveraging ferroptosis as a cancer therapy has faced challenges due to the limited bioavailability and systemic toxicities of small-molecule ferroptosis modulators. Small molecule inhibitors such as RSL3 and ML210 trigger ferroptosis by targeting glutathione peroxidase 4 (GPX4), a key enzyme that neutralizes lipid peroxides. While many studies have focused on targeting primary tumors, much less is known about the extent to which GPX4-inhibitor resistance may contribute to metastasis.

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KDM6A alternative splicing induced by 25(OH)D inhibits breast cancer cell stemness through repressing TRAP1 transcription. reports: 25-Hydroxyvitamin D (25(OH)D), a metabolite of vitamin D, has demonstrated anticancer properties; however, the role of alternative splicing in mediating these effects remains poorly understood. In this study, we reveal for the first time that 25(OH)D exerts antitumor effects by promoting exon 13 skipping of KDM6A (KDM6A Δexon13), which suppresses the proliferation and stemness of breast cancer cells and lacks H3K27 demethylase activity. Mechanistically, CUT&Tag and RNA-seq analyses demonstrated that KDM6A Δexon13 induces the accumulation of H3K27me3 at the promoter region of TRAP1, thereby inhibiting its transcription.

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Metastatic breast cancer presenting with dyspeptic symptoms: a case report. reports: Breast cancer is among the most commonly diagnosed malignancies worldwide. While distant metastases typically involve the bone, lung, liver, and brain, metastasis to the gastrointestinal tract is uncommon and occurs disproportionately in invasive lobular carcinoma (ILC). The clinical presentation is often nonspecific, which can delay diagnosis.

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Prevalence of KDM6A deficiency in human cancer: A tissue microarray study on 18,570 cancers from 153 different tumor types. reports: KDM6A is a critical part of the COMPASS-like complex. KDM6A deficiency may result in EZH2 dependency. KDM6A deficiency was analyzed by immunohistochemistry on a tissue microarray containing 14,814 samples from 153 different tumor entities and 76 different normal tissue types.

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Synthesis and Biological Evaluation of 3,5-Diaryl-Substituted 1,2,4-Oxadiazole Sulfamates as Potent Steroid Sulfatase Inhibitors. reports: A novel series of 3,5-disubstituted 1,2,4-oxadiazole sulfamates was synthesized and evaluated as steroid sulfatase (STS) inhibitors. Molecular docking predicted high affinity (binding energies of up to -8.9 kcal·mol -1 ), often surpassing the reference Irosustat. Biological evaluation confirmed potent inhibition; compound 9n reduced enzymatic STS activity to 3.5% at 10 μM.

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Magnetic graphene-based ferrite nanoparticles: synthesis, characterization, and anti-proliferative activity against some human cancer cells ( in vitro study). reports: This work introduces a novel soft magnetic building block (GCM), based on reduced graphene oxide covalently functionalized with Congo red molecules and incorporated with barium ferrite nanoparticles, creating a promising multifunctional platform for future magnetically controlled nanorobotic systems for potential cancer therapy and diagnosis nanodevices. The sol-gel auto-combustion method was used for the synthesis of pure barium ferrite (M) and in situ synthesis of reduced graphene oxide-barium ferrite nanoconjugate (GM). Physicochemical characterization techniques were used for identification, including infrared spectroscopy, X-ray diffraction, UV-visible spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy-dispersive X-ray spectroscopy, high-resolution transmission electron microscopy, vibrating sample magnetometry, size distribution analysis, and ζ -potential analysis.

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The effect of two remote exercise programs on cardiorespiratory fitness, cardiac function, and vascular health in patients with breast cancer. reports: Breast cancer is a common, survivable malignancy affecting women. With improved survival, the off-target effects of chemotherapy, such as a decline in cardiorespiratory fitness and worse cardiovascular outcomes, have been recognized. Exercise training may help mitigate these effects.

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Acute Portal Vein Thrombosis Associated With Anastrozole Therapy: A Report of a Rare Case. reports: Portal vein thrombosis (PVT) is a rare but potentially life-threatening condition that most often occurs in the setting of liver disease, malignancy, local inflammation, certain medications, or hypercoagulable disorders. We report a rare case of acute PVT in a 71-year-old woman with a history of breast cancer in remission who was receiving adjuvant anastrozole therapy and presented with abdominal pain. CT revealed extensive thrombosis involving the portal vein and superior mesenteric vein.

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Evaluation of Ginsenosides and Their Derivatives From Panax ginseng as Aromatase Inhibitors for Breast Cancer Treatment-An in silico study. reports: Breast cancer, particularly estrogen receptor-positive subtypes, is a leading cause of cancer-related mortality worldwide. Aromatase inhibitors, which target estrogen biosynthesis, are a cornerstone of therapeutic intervention. Panax ginseng , a widely recognized medicinal herb, contains bioactive compounds known as ginsenosides, which possess various pharmacological activities, including anticancer properties.

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Evaluation of trimetazidine in alleviating paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled trial. reports: Paclitaxel-induced peripheral neuropathy is a frequent chemotherapy complication that causes nerve damage and profoundly reduces patients' quality of life. Despite extensive preclinical evidence supporting the neuroprotective potential of trimetazidine against peripheral neuropathy, its clinical efficacy remains unexplored. This proof-of-concept randomized controlled trial aimed to investigate the effect of trimetazidine administered during the early phase of treatment on the incidence of paclitaxel-induced peripheral neuropathy in patients with non-metastatic breast cancer.

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Impact of breast implant presence and type on mean glandular dose calculations. reports: Breast cancer remains the most frequently diagnosed cancer among women, making mammography a vital tool for its early detection. However, the increasing prevalence of breast augmentation raises concerns about the accuracy of radiation dose estimation during mammography. This study investigates the impact of breast implants on mean glandular dose (MGD) calculations in mammography using Monte Carlo simulations.

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Validation of Chinese medicine syndrome differentiation in early breast cancer: a multicenter prospective clinical study. reports: Breast cancer is the most common cancer among women. Chinese herbal medicine, which is based on accurate Chinese medicine (CM) syndrome diagnosis, plays a vital role during cancer treatment. This study aimed to validate the established CM syndrome diagnostic criteria for early breast cancer, enhancing their application in clinical settings.

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Radiation-Induced Autophagy Regulates the Fibroblast Mitochondrial Stress Response and Crosstalk with Triple-Negative Breast Cancer Cells reports: Patients with triple-negative breast cancer (TNBC) experience high recurrence rates despite current interventions, which includes radiation therapy (RT). Tumor cells thought to be involved in recurrence survive in part due to their interactions with irradiated fibroblasts following treatment. How fibroblasts metabolically respond to RT and influence the behavior of TNBC cells is poorly understood. This is a preprint and not peer reviewed.

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Gene Set Analysis for time-to-event outcome with the Generalized Berk-Jones statistic reports: Gene set analysis evaluates the collective impact of groups of genes on an outcome of interest, such as disease occurrence. By incorporating biological knowledge through predefined gene sets, this approach enhances the interpretability of results and improves statistical power compared to gene-wise analyses. In the context of time-to-event data, existing methods are limited and fail to account for potentially strong correlations within gene sets. This is a preprint and not peer reviewed.

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Drug combination prediction for cancer treatment using disease-specific drug response profiles and single-cell transcriptional signatures reports: Developing novel cancer treatments is a challenging task that can benefit from computational techniques matching transcriptional signatures to large-scale drug response data. Here, we present retriever, a tool that extracts robust disease-specific transcrip-tional drug response profiles based on cellular response profiles to hundreds of compounds from the LINCS-L1000 project. We used retriever to extract transcriptional drug response signatures of triple-negative breast cancer (TNBC) cell lines and combined these with a single-cell RNA-seq breast cancer atlas to predict drug combinations that antagonize TNBC-specific disease signatures. This is a preprint and not peer reviewed.

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KDM2B Silencing Elicits a Paracrine Mechanism Which Destabilizes SLUG, Promoting Differentiation of Basal-Like Breast Cancer Cells. reports: KDM2B is a JmjC domain H3K36me2/H3K36me1 demethylase, which immortalizes cells in culture and contributes to the biology of both embryonic and adult stem cells, including cancer stem cells. Here we show that the silencing of KDM2B activates a tyrosine kinase receptor-dependent paracrine mechanism, which results in the downregulation of SNAI2 (SLUG), SNAI1 (SNAIL) and SOX9, which also contribute to the biology of stem and progenitor cells. The downregulation of these molecules is posttranscriptional and in the case of SNAI2-encoded SLUG, it is due to calpain-dependent proteolytic degradation. This is a preprint and not peer reviewed.

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Breast cancer multigene germline panel testing in mainstream oncology based on clinical-public health utility (cancer mortality benefit): ESMO Precision Oncology Working Group recommendations reports: BackgroundWith widening therapeutic indications, germline genetic testing is offered to an increasing proportion of patients with breast cancer (BC) via mainstream oncology services. However, the gene set tested varies widely from just BRCA1/BRCA2 through to pan-cancer panels of near 100 genes. If a germline pathogenic variant (GPV) is detected, the BC proband and other family GPV-carriers may be offered interventions such as risk-reducing surgery and decades of intensive surveillance for the various cancers linked to that gene. This is a preprint and not peer reviewed.

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Causal associations between gut microbiota and cancers reports: BackgroundEmerging evidence suggests that the gut microbiota is associated with various cancer-related outcomes. Recent studies using Mendelian randomization (MR) have indicated a causal relationship between gut microbiota and several types of cancer. However, these conclusions remain controversial. This is a preprint and not peer reviewed.

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Investigating the relationship between breast cancer risk factors and an AI-generated mammographic texture feature in the Nurses' Health Study II reports: IntroductionThe mammogram risk score (MRS), an AI-driven texture feature derived from digital mammograms, strongly predicts breast cancer risk independently of breast density, though underlying mechanisms remain unclear. This study investigated relationships between established breast cancer risk factors, covering anthropometrics, reproductive factors, family history, and mammographic density metrics, and MRS. MethodsUsing data from the Nurses Health Study II (292 cases, 561 controls), we validated MRSs association with breast cancer using logistic regression and evaluated its relationships with risk factors through: linear regressions of MRS on observed risk factors and polygenic scores associated with risk factors, and Mendelian randomization (MR) analysis via two-stage least squares regression. This is a preprint and not peer reviewed.

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Cancer risks for MSH6 pathogenic variant carriers reports: IntroductionLynch syndrome (LS) is a hereditary cancer syndrome caused by (likely) pathogenic variants (LP/P) in DNA mismatch repair genes, including MSH6. It is associated with elevated lifetime risks for colorectal cancer (CRC), endometrial cancer (EC), and other malignancies. However, cancer risks specific to MSH6-associated LS, particularly for non-colorectal cancers, remain poorly defined. This is a preprint and not peer reviewed.

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Case Report: Primary cutaneous apocrine carcinoma mimicking breast carcinoma - a rare diagnostic challenge. reports: A 60-year-old male patient presented to a senological clinic with a left axillary tumor. The histomorphological characteristics were ambiguous, initially pointing to apocrine carcinoma of mammary origin. This suspicion led to a delay in establishing the correct diagnosis.

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From genetic risk to early detection - clinical outcomes of a person-centered screening program for women with a high genetic risk of breast cancer. reports: There is little evidence on breast cancer (BC) diagnosed in women with a high genetic risk, before and after their inclusion in a long-term risk management program based on genetic risk assessment. We analyzed clinical outcomes in women enrolled in the Phare Grand Ouest (PGO) program. The PGO includes carriers of the BRCA1 and BRCA2 pathogenic variants (PV) and women at high risk without BRCA PV , enrolled in eight cancer genetics units.

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