HER-2 mutation

Patients with HR+ /HER2+ BC had lower risks of breast cancer-specific death and higher overall survival rates. Mast cells were enriched in the HR+ /HER2+ BC group, while plasma cells were more abundant in the HR-/HER2+ BC group.In conclusion, HER2+ BC patients benefit differently from current HER2-directed therapies, maybe partly due to the HR status and gene mutations, and they may provide potentially prognostic and predictive value and new treatment strategies for clinicians.

We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.

The HER2 copy number level did not show additional value in distinguishing subgroups. Conclusions highlight the need to address CNB-SEB diagnostic discordance, particularly in ultralow cases, emphasizing the necessity of HER2 retesting in surgical specimens.

Altogether, these findings were insufficient to establish a diagnosis of pcGDTCL. We review the clinical, histopathologic, and molecular sequencing data pertaining to our rare patient as well as the recent literature on indolent CD30+LPD with gamma-delta T-cells.

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

P3, N=240, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting

P1/2, N=315, Active, not recruiting, Dizal Pharmaceuticals | Trial completion date: Jul 2025 --> Dec 2025

In September 2025, imlunestrant was approved for the treatment of adults with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy in the USA. This article summarizes the milestones in the development of imlunestrant leading to this first approval for use in patients with ER+, HER2-, ESR1-mutated advanced or metastatic breast cancer.

Based on gene ontology analysis, we additionally show that these genes have plausible connections to breast cancer biology that should be experimentally investigated. Here, we demonstrate the utility of the unsupervised random forest model over K-means clustering for identifying important genes in breast cancer.

ERBB2 focal amplification is associated with improved outcomes in trastuzumab-treated patients with HER2-positive gastric cancer, whereas NOTCH3 alterations predict a poor prognosis. These genomic features may support risk stratification and therapeutic decisions.