HR positive

Patients meeting IHC 0 with membrane staining (HER2-ultralow) criteria may benefit from HER2-targeted therapies such as trastuzumab deruxtecan...These findings highlight potential challenges of identifying HER2-ultralow expression and suggest the need for enhanced pathologist training, adherence to best practices, and integration of digital pathology and artificial intelligence solutions. Trial Registration: ClinicalTrials.gov_identifier: NCT03734029.

Patients with MammaPrint H2 tumors had a clinically meaningful benefit from anthracycline-containing chemotherapy, whereas patients with H1 tumors did not derive more benefit from AC-T than from TC despite overlapping high-risk features. These findings support the use of MammaPrint to inform chemotherapy regimen selection and warrant further validation.

Multiple heterozygosity in HBOC core genes is more frequent than previously assumed. Our data indicate that gene-gene constellations can reshape tumour phenotype and clinical severity rather than following single-gene expectations. Integrating multiple pVs into risk assessment and counselling may enhance personalised surveillance and risk-reducing strategies for DH individuals and their families in the era of widespread multigene testing.

The combination of palbociclib and tamoxifen delayed deterioration in patients' QoL while they experienced reduced risk for disease progression.

Collectively, these findings identify E545A as a functionally active and therapeutically consequential PIK3CA variant. Our study expands the current understanding of PIK3CA-driven oncogenic diversity beyond canonical hotspot mutations and underscores the need for variant-resolved stratification to improve the efficacy of PI3K-targeted therapies.

In this comparative study, CDK4/6 inhibitor-based therapy was associated with significantly higher prevalence and severity of punctate epitheliopathy and vortex keratopathy, independent of aromatase inhibitor exposure and in the absence of measurable tear film dysfunction. These findings suggest a direct cytostatic effect on the corneal epithelium. Among respondents, symptom scores were uniformly low; however, the incomplete OSDI response rate in the CDKAI group limits definitive conclusions regarding symptom burden. Proactive corneal surface evaluation with fluorescein staining may be warranted during CDK4/6 inhibitor treatment.

SGLT2 inhibition represents a promising systems-level strategy at the intersection of cardio-oncology, metabolism, and endocrine resistance in HR+ breast cancer. By simultaneously targeting glucose homeostasis, adipose tissue dysfunction, and lipid metabolism, SGLT2i may improve both cardiovascular outcomes and long-term cancer control. Dedicated prospective trials are urgently needed to define their clinical role in breast cancer survivorship and precision cardio-oncology.

This integrative analysis characterized the ribociclib pharmacokinetic and exposure-QTcF relationship, revealed the population effect on both pharmacokinetic and QTcF response, and justified the 400-mg dose in EBC. This work illustrates the utility and impact of quantitative pharmacology in justifying different doses across different patient populations for oncology therapies.

The incidence of anemia (43.9% versus 28.3%, p = 0.01), ≥grade 3 anemia (9.8% versus 1.9%, p = 3.10E-03), ≥grade 3 thrombocytopenia (9.8% versus 1.9%, p = 3.10E-03), ≥grade 3 ALT (6.1% versus 0.4%, p = 3.10E-03) and AST (7.3% versus 1.9%, p = 0.02) dysfunction occurred more frequently in the high-altitude group. Patients with HR+/HER2- ABC in the high-altitude region experienced inferior survival outcomes and individualized tolerability to CDK4/6i, which may inform scientific research and the management of CDK4/6i in Chinese patients with HR+/HER2- ABC.

Breast cancer cells (i.e., MCF7 and MDA-MB231) infected with a combination of recombinant HSV-1 viruses that express granulocyte-macrophage colony-stimulating factor (GM-CSF) and metformin exhibit a synergistic effect in promoting the expression of interferon-ϒ (IFN-ϒ) found within peripheral blood mononuclear cells (PBMCs) and exerting apoptotic and cytotoxic effects in the mentioned malignant cells. The online version contains supplementary material available at 10.1007/s12088-025-01523-7.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (such as palbociclib, ribociclib, and abemaciclib) exert their effects by arresting the cell cycle at the G1/S checkpoint. From the perspective of laboratory medicine, we further emphasize the importance of biomarker detection, therapeutic target assessment, and precision molecular subtyping in identifying patients most likely to benefit from CDK4/6 inhibitor-based therapies. In addition, we discuss the role of these agents in remodeling the TIME, evaluate current combination strategies aimed at overcoming resistance, and highlight future directions for advancing this rapidly evolving field.

Additionally, we uncovered a unique mechanism of clearance driven by both metabolism and efflux in rats and demonstrated that we could counter efflux-driven clearance with high permeability. Our efforts resulted in compound 19, which was potent against CDK2, exhibited good selectivity vs CDK4 and CDK1, and had pharmacokinetic properties that enabled evaluation in a CDK2 xenograft model of cancer, where it achieved nearly 80% tumor growth inhibition.