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Adrenomedullin Antagonist Nanoparticles Inhibit Breast Cancer Brain Metastasis by Immunomodulating Monocytes/Macrophages - PubMed
2 months ago
- Breast cancer brain metastasis (BCBM) is difficult to treat due to the blood-brain barrier (BBB).
- Monocytes, M2 macrophages, and adrenomedullin (AM) are abundant in human BCBM.
- HPPS nanoparticles effectively target monocytes/macrophages.
- AMA-HPPS nanoparticles can immunomodulate monocytes/macrophages into antitumor effector cells.
- AMA-HPPS-CpG enhances monocyte targeting and immunomodulation, inhibiting BCBM and prolonging survival in mice.
- The nanoparticles activate the NF-κB pathway, reprogramming the immunosuppressive tumor microenvironment.
- This study presents a novel immunotherapy strategy for brain metastasis by targeting monocytes/macrophages.
Refining Risk Assessment for Adjuvant CDK4/6 Inhibitors beyond Trial Inclusion Criteria: Integrating Recurrence Score and Endocrine Responsiveness according to ADAPT - PubMed
2 months ago
- The study focuses on refining risk assessment for adjuvant CDK4/6 inhibitors in HR+/HER2- high-risk early breast cancer (eBC) beyond trial inclusion criteria.
- It integrates recurrence score (RS) and endocrine responsiveness based on the WSG-ADAPT-HR+/HER2- trial.
- Key trials referenced include NATALEE and monarchE, which showed improved survival with CDK4/6 inhibitors added to endocrine therapy (ET), though benefits vary by prognostic factors.
- Patients were categorized into low, intermediate, and high-risk groups based on NATALEE and monarchE criteria.
- Findings indicate that intermediate-risk patients (meeting NATALEE but not monarchE criteria) had slightly inferior outcomes compared to low-risk patients but could still benefit from CDK4/6 inhibitors.
- ET-response evaluation (Ki67 post-ET ≤10%) was crucial in refining prognosis and guiding treatment decisions.
- 5-year invasive disease-free survival (iDFS) and distant DFS (dDFS) rates were highest in low-risk groups and decreased progressively in intermediate and high-risk groups.
- The study suggests an absolute benefit of ~2% fewer dDFS events in intermediate-risk patients if treated with ribociclib, based on a hazard ratio of 0.7.
- The research underscores the importance of ET-response in shared decision-making for intermediate-risk patients.
Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression: The BRIGHT-2 Phase 3 Randomized Clinical Trial - PubMed
a month ago
- The BRIGHT-2 trial evaluated bireociclib plus fulvestrant in HR-positive, ERBB2-negative advanced breast cancer (ABC) after endocrine therapy progression.
- This phase 3 randomized clinical trial involved 305 patients, with a 2:1 randomization to bireociclib plus fulvestrant (204 patients) or placebo plus fulvestrant (101 patients).
- Bireociclib plus fulvestrant significantly improved progression-free survival (PFS) compared to placebo (median PFS 14.7 months vs. 7.3 months; HR 0.54, P < .001).
- The objective response rate was higher in the bireociclib group (45.6% vs. 14.9%) with a prolonged median duration of response.
- Safety profiles were consistent with known cyclin-dependent kinase 4/6 inhibitors, and subgroup analyses showed consistent PFS benefits across various patient characteristics.
- Patients with early-onset diarrhea appeared to derive more benefit from bireociclib (HR 0.49).
- The study confirms bireociclib plus fulvestrant as a viable treatment option for HR-positive, ERBB2-negative ABC with manageable safety.
Patient-derived xenograft models of primary breast cancer for preclinical evaluation of neoadjuvant therapies - PubMed
a month ago
- Patient-derived xenograft (MIND-PDX) models were developed for preclinical evaluation of neoadjuvant therapies in primary breast cancer.
- A cohort of 60 MIND-PDX models representing all subtypes of invasive breast cancer (IBC) was created, along with seven matched PDX-derived organoids.
- The study demonstrated that adding a PARP inhibitor did not benefit neoadjuvant treatment for triple-negative IBC.
- For estrogen receptor-positive IBC, combining a CDK4/6 inhibitor with fulvestrant improved neoadjuvant treatment response.
- The IBC-MIND cohort serves as a valuable resource for studying breast cancer biology and developing neoadjuvant treatments.
Regulation of the immune CD155-CD226-TIGIT axis by cyclin D-CDK4/6 - PubMed
a month ago
- Cyclin D-CDK4/6 regulates the CD155-CD226-TIGIT immune axis.
- CDK4/6 inhibition upregulates CD155 in cancer cells and downregulates TIGIT in lymphocytes.
- Effects observed in human breast cancer cell lines, mouse models, and patient biopsies.
- CDK4/6 inhibition may shift balance from immunoinhibitory CD155-TIGIT to immunostimulatory CD155-CD226.
- Combination of CDK4/6 inhibitors and anti-TIGIT antibodies could enhance antitumor immunity.
- Study suggests potential for synergistic antitumor effects with combined therapy.
Ticagrelor reverses multidrug resistance in breast cancer by inhibiting PI3K/AKT/mTOR pathway and suppressing ABCB1 expression and function - PubMed
a month ago
- Ticagrelor reverses multidrug resistance (MDR) in breast cancer by inhibiting the PI3K/AKT/mTOR pathway.
- It suppresses ABCB1 expression and function, enhancing the cytotoxicity of chemotherapeutic agents like Adriamycin and Paclitaxel.
- Ticagrelor combined with Adriamycin downregulates PI3K/mTORC1 and PI3K/mTORC2 signaling pathways and reduces EMT-related protein levels.
- In xenograft models, Ticagrelor and Adriamycin combination significantly suppresses tumor growth compared to monotherapy.
- The study highlights Ticagrelor's potential as a dual-acting agent targeting both tumor metastasis and chemoresistance.
Exploring the mechanism of action of abemaciclib in breast cancer through circulating chromatin fragments - PubMed
a month ago
- Abemaciclib, a CDK4/6 inhibitor, was studied in metastatic recurrent breast cancer patients using cfDNA analysis.
- cfDNA concentrations were higher in breast cancer patients than in healthy individuals and decreased after abemaciclib treatment.
- Sequencing revealed distinct cfDNA signatures in treated vs. untreated samples, particularly in chromatin regions linked to cell death and CDK4/6-regulated pathways.
- Differences in chromatin features were observed between long-term responders and short-term progression cases.
- Pathway analysis identified the Polycomb complex as a potential modulator of treatment efficacy, with EZH2 inhibition enhancing abemaciclib's anti-proliferative effect.
- cfDNA profiling may serve as a practical biomarker for monitoring treatment response and predicting efficacy in breast cancer therapy.
Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression - PubMed
a month ago
- Hepatic dysfunction modulates breast cancer progression through metabolic, endocrine, and inflammatory crosstalk.
- Five key pathways identified: insulin resistance-driven IGF1-PI3K/AKT activation, estrogen metabolism imbalance, IL6-STAT3/NLRP3-mediated inflammation, HMOX1/APOE-dependent metabolic rewiring, and FAK-Src/MMP9-regulated ECM remodeling.
- Key molecular mediators include nuclear receptors (ESR1), cytokines (IL-1β), growth factors (HGF), and receptor tyrosine kinases.
- SPP1 and PTPN2 identified as potential circulating biomarkers linking hepatic dysfunction to aggressive breast cancer phenotypes.
- The study suggests potential therapeutic targets and emphasizes the need for translational validation and personalized strategies for breast cancer patients with liver conditions.
Use of ctDNA in Older Women with ER+ Breast Cancer to Facilitate Surgical De-escalation: A Prospective, Hybrid-Decentralized Trial with Correlative Studies - PubMed
a month ago
- Study explores ctDNA's role in older women with ER+ breast cancer to identify candidates for surgical de-escalation.
- Prospective, hybrid-decentralized trial (n=43) linked ctDNA levels with tumor progression in patients opting for primary endocrine therapy (pET) over surgery.
- Pretreatment ctDNA positivity significantly associated with tumor progression (HR, 30; 95% CI, 4.4-209; P=0.0011); no progression in ctDNA-negative cases.
- Correlative analyses revealed immunosuppressive macrophages in ctDNA-positive tumors progressing on pET, fostering cancer cell proliferation.
- Findings suggest ctDNA as a tool to safely guide long-term pET use in older patients, warranting randomized trials.
Omission of axillary surgery in early breast cancer with negative lymph nodes: a systematic review and meta-analysis of randomized clinical trials - PubMed
a month ago
- Omission of axillary surgery in early-stage breast cancer with clinically negative lymph nodes does not negatively impact overall survival (OS) or disease-free survival (DFS).
- A systematic review and meta-analysis of 7 randomized clinical trials (RCTs) involving 8806 patients was conducted.
- No significant differences were found in OS (OR = 1.02; 95% CI, 0.86-1.20; p = 0.84) or DFS (OR = 0.80; 95% CI, 0.63-1.00; p = 0.05) between patients who underwent no axillary surgery and those who received standard axillary interventions.
- Axillary recurrence (AR) was significantly lower in the axillary surgery group (OR = 0.18; 95% CI, 0.10-0.31; p < 0.01).
- The study followed PRISMA guidelines and was registered in PROSPERO (CRD420250653779).
Programmable nanomicelles rewire myeloid immunity for durable control of primary and metastatic breast cancer - PubMed
a month ago
- Programmable nanomicelles target myeloid immunity to control primary and metastatic breast cancer.
- Nanomicelles co-deliver IR825, anti-PD-L1 antibodies, and antagomiR-182 with precision.
- Induces immunogenic cell death, promoting dendritic cell maturation for better antigen presentation.
- miR-182 inhibition repolarizes M2-like macrophages into M1-like phenotypes via TLR4/MYD88/NF-κB pathway.
- Enhances CD8+ T cell infiltration and functionality, leading to durable anti-tumor responses.
- Shows efficacy in suppressing tumor growth, preventing metastasis, and inducing immune memory.
- Validated in patient-derived tumor fragment assays and xenograft models, indicating translational potential.
Differences in distant metastasis risk of breast cancer originating from various primary sites: a retrospective analysis based on the SEER database - PubMed
a month ago
- Breast cancer's primary site diversity influences distant metastasis patterns and patient survival.
- Study includes 240,943 female breast cancer patients from SEER data (2010-2019).
- Primary sites classified into UIQ, LIQ, UOQ, LOQ, axillary tail, overlapping region, and TCNP.
- Distant metastatic organs include bone, brain, liver, and lung.
- Axillary tail tumors have higher risk of bone and lung metastasis compared to UOQ.
- UIQ tumors linked to lower risk of bone metastasis; TCNP has higher risk of bone and liver metastasis.
- Brain metastasis indicates poorer prognosis than bone metastasis.
- Primary site impact on survival less significant when metastasis occurs in the same organ.
- Findings may help focus preventive measures on susceptible organs early in diagnosis.
Investigating the mechanistic link between pesticide DDT and breast cancer through network toxicology, molecular docking, and molecular dynamics simulation - PubMed
a month ago
- Study investigates the link between pesticide DDT and breast cancer using network toxicology, molecular docking, and molecular dynamics simulation.
- Identified 12 DDT-associated breast cancer targets, including AR, ESR1, ESR2, and ERBB2, involved in hormone and growth factor signaling pathways.
- Highlights the need for further epidemiological and clinical studies to understand DDT's impact on breast cancer risk.
- Data sourced from publicly available databases like TCGA and GEO, ensuring no ethical concerns.
- Findings could inform future prevention and treatment strategies related to DDT exposure and breast cancer.
Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial - PubMed
a month ago
- Study evaluates dalpiciclib plus chidamide in HR+/HER2- advanced breast cancer after CDK4/6 inhibitor failure.
- Phase Ib trial identifies maximum tolerated dose (MTD) as group C (dalpiciclib 100 mg/d, chidamide 25 mg BIW).
- Common grade 3-4 adverse events include neutropenia (100%), leukopenia (64%), and thrombocytopenia (36%).
- Objective response rate (ORR) is 9.1% overall and 16.7% at MTD.
- Median progression-free survival (PFS) is 5.8 months overall and 12.3 months at MTD.
- Patients with PIK3CA mutations have shorter median PFS compared to wild type.
- Combination therapy shows manageable safety and preliminary antitumor activity post-CDK4/6 inhibitor failure.
The BMP Inhibitor Coco Reactivates Breast Cancer Cells at Lung Metastatic Sites - PubMed
a month ago
- The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites.
- Original study published in Cell (2012) with DOI: 10.1016/j.cell.2012.06.035.
- Erratum or related content published in Cell (2026) with DOI: 10.1016/j.cell.2026.03.026.
- Study focuses on the role of BMP inhibition in breast cancer metastasis to the lungs.
A multi-ancestry genome-wide study of tamoxifen metabolism and breast cancer recurrence - PubMed
a month ago
- Study on tamoxifen metabolism and breast cancer recurrence across multiple ancestries.
- CYP2D6 metabolizer status is the primary predictor of steady-state Z-endoxifen levels.
- TCF20 rs932376 A > G has a smaller, independent effect on endoxifen levels.
- Neither CYP2D6 metabolizer status nor TCF20 rs932376 A > G was significantly associated with breast cancer outcomes.
- Findings were validated in independent cohorts.
A localization gate licenses chaperone-mediated autophagy of SNAI (snail) to restrain epithelial-mesenchymal transition competence in breast cancer - PubMed
a month ago
- SNAI (snail) is a key regulator of epithelial-mesenchymal transition (EMT) in breast cancer.
- SNAI is identified as a substrate of chaperone-mediated autophagy (CMA), with its degradation controlled by nucleocytoplasmic trafficking.
- Depletion of CMA components (HSPA8/HSC70 or LAMP2A) increases SNAI levels and extends its half-life.
- A CMA-resistant SNAI mutant enhances EMT outputs, including migration, invasion, and metastasis.
- In triple-negative breast cancer, SNAI is predominantly nuclear, making it inaccessible to CMA under normal conditions.
- Serum starvation promotes SNAI nuclear export, enabling CMA-dependent degradation, which can be blocked by leptomycin B.
- The study suggests enhancing CMA or promoting cytosolic exposure of SNAI could attenuate EMT-driven cancer progression.
Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy in early breast cancer - PubMed
a month ago
- Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) does not necessarily prevent brain metastases in early-stage breast cancer (BC).
- The study analyzed 1147 stage I-III BC patients treated with NAC and surgery, focusing on CNS recurrence patterns by BC subtypes (HR-positive/HER2-negative, HER2-positive, TNBC).
- CNS recurrence occurred in 6.2% of patients, with no significant difference between pCR and non-pCR groups overall, but pCR reduced CNS recurrence risk in HER2-positive BC.
- Isolated CNS relapse was the most common pattern (82.4%) in pCR patients, especially in HER2-positive cases.
- Median overall survival after CNS relapse was 12 months.
- HER2-positive, TNBC, and cN2-3 status were identified as independent predictors of CNS recurrence.
Subtype-specific APOBEC enrichment links genomic instability to predict immunotherapy response in breast cancer subtypes - PubMed
a month ago
- Breast cancer (BRCA) significantly impacts women's survival quality and life expectancy, with rising incidence and mortality rates.
- Study investigates APOBEC family genes' genomic characteristics across BRCA subtypes and their influence on mutation profiles.
- APOBEC mutation enrichment scores (APMs) are significantly elevated in BRCA, with HER2+ showing the highest and TNBC the lowest.
- Correlations found between APMs and tumor mutational burden (TMB), suggesting differential immune microenvironment interactions.
- APMs associated with DNA damage response pathways, impacting treatment strategies.
- APOBEC mutagenesis-related prognostic risk score (AMrs) predicts immunotherapy response in BRCA subtypes (TNBC, Luminal, HER2+).
- Specific agents combined with anti-PD-1 therapy boost effectiveness and transform tumor immunological environment in mice.
- Synergistic approach led to reduced tumor volume and increased cytotoxic T cell density in experiments.
- APOBEC family genes' role in BRCA heterogeneity highlights potential as biomarkers for personalized therapy.
Impact of pathologic response and individual prognosis after neoadjuvant treatment in patients with early HER2+ and triple-negative breast cancer - PubMed
a month ago
- Pathologic complete response (pCR) after neoadjuvant treatment (NAT) is prognostic for recurrence-free survival (RFS) and overall survival (OS) in breast cancer (BC).
- Study assessed prognostic factors for RFS and OS in patients with pCR compared to residual disease (RD) in HER2+ and triple-negative breast cancer (TNBC).
- 863 patients (median age 50.2) underwent surgery from 2016 to 2021, with a median follow-up of 3.5 years.
- Three-year RFS was 87% overall, 93% in HER2+, and 80% in TNBC cohorts.
- Among 374 pCR patients (43.3%), 3-year RFS was 98%, compared to 79% in 489 RD patients (56.7%).
- In HER2+ BC, 3-year RFS was 99% for pCR vs. 87% for RD, while in TNBC it was 97% for pCR vs. 72% for RD.
- Higher cT, positive cN, TNBC subtype, and RD were associated with poorer RFS and OS.
- In pCR, 3-year RFS was numerically higher in cT1-2 compared to cT3-4 and in cN0 compared to cN+ (not significant).
- In RD, higher cT, positive cN, and TNBC subtype remained associated with poorer outcomes.
- Multivariate analysis found no associations in pCR patients.
- Conclusion: Patients experiencing pCR had better outcomes. cT, cN, and subtype were prognostic only in patients with RD.

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#breast cancer

Adrenomedullin Antagonist Nanoparticles Inhibit Breast Cancer Brain Metastasis by Immunomodulating Monocytes/Macrophages - PubMed

Refining Risk Assessment for Adjuvant CDK4/6 Inhibitors beyond Trial Inclusion Criteria: Integrating Recurrence Score and Endocrine Responsiveness according to ADAPT - PubMed

Bireociclib Plus Fulvestrant in Advanced Breast Cancer After Endocrine Progression: The BRIGHT-2 Phase 3 Randomized Clinical Trial - PubMed

Patient-derived xenograft models of primary breast cancer for preclinical evaluation of neoadjuvant therapies - PubMed

Regulation of the immune CD155-CD226-TIGIT axis by cyclin D-CDK4/6 - PubMed

Ticagrelor reverses multidrug resistance in breast cancer by inhibiting PI3K/AKT/mTOR pathway and suppressing ABCB1 expression and function - PubMed

Exploring the mechanism of action of abemaciclib in breast cancer through circulating chromatin fragments - PubMed

Multi-omic analysis of the liver-breast axis reveals key hepatic mediators of breast cancer progression - PubMed

Use of ctDNA in Older Women with ER+ Breast Cancer to Facilitate Surgical De-escalation: A Prospective, Hybrid-Decentralized Trial with Correlative Studies - PubMed

Omission of axillary surgery in early breast cancer with negative lymph nodes: a systematic review and meta-analysis of randomized clinical trials - PubMed

Programmable nanomicelles rewire myeloid immunity for durable control of primary and metastatic breast cancer - PubMed

Differences in distant metastasis risk of breast cancer originating from various primary sites: a retrospective analysis based on the SEER database - PubMed

Investigating the mechanistic link between pesticide DDT and breast cancer through network toxicology, molecular docking, and molecular dynamics simulation - PubMed

Dalpiciclib plus chidamide in HR + /HER2-advanced breast cancer after CDK4/6 inhibitor failure: a phase Ib trial - PubMed

The BMP Inhibitor Coco Reactivates Breast Cancer Cells at Lung Metastatic Sites - PubMed

A multi-ancestry genome-wide study of tamoxifen metabolism and breast cancer recurrence - PubMed

A localization gate licenses chaperone-mediated autophagy of SNAI (snail) to restrain epithelial-mesenchymal transition competence in breast cancer - PubMed

Risk of CNS relapse following pathological complete response to neoadjuvant chemotherapy in early breast cancer - PubMed

Subtype-specific APOBEC enrichment links genomic instability to predict immunotherapy response in breast cancer subtypes - PubMed

Impact of pathologic response and individual prognosis after neoadjuvant treatment in patients with early HER2+ and triple-negative breast cancer - PubMed