HER-2 positive

P3, N=19, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

In an independent validation cohort (n = 120), higher POSTN expression was associated with inferior disease-free survival. Collectively, these results nominate POSTN as a potential prognostic biomarker and support ECM-centered and PI3K-AKT-related mechanisms as actionable biological features of lymph-node metastasis in HER2-positive breast cancer.

However, with the development of resistance, the tumor microenvironment shifted to an immunosuppressive state, characterized by reactivation of transforming growth factor-beta signaling and upregulation of programmed cell death protein-1 (PD-1). These findings provide novel insights into mechanisms underlying T-DXd resistance and highlight potential therapeutic targets for overcoming T-DXd resistance in GC.

High post-NAT tumor-infiltrating lymphocytes correlated strongly with pCR (r = 0.67, p < 0.001). Thus, we show that NAT induces significant histomorphological changes, which can serve as key prognostic indicators for therapeutic response and patient outcomes.

These findings support a model in which CBD downregulates HER2 and, in a HER2-dependent context, promotes paraptosis and ferroptosis. In addition, docking and molecular dynamics analyses suggested a potential interaction between CBD and HER2, providing mechanistic insights into possible molecular recognition relevant to HER2-positive breast cancer.

In patients with BCBM, T-DXd-associated ILD/pneumonitis occurred in 10% of patient and frequently necessitated treatment modification. Although no fatal ILD was observed, the high discontinuation rate underscored the imperative for vigilant monitoring and protocol-guided management to mitigate pulmonary toxicity while preserving intracranial efficacy.

P2, N=168, Recruiting, Canadian Cancer Trials Group | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Jun 2026

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Higher HER2-HQE is associated with increased RCB. Quantifying HER2 heterogeneity via HQE and percentage of HER2 IHC 3+ may help optimize therapeutic strategies in clinical practice.

Tumor histology affects the real-world effectiveness of first line ET plus CDK4/6i. In ILC, all three CDK4/6i performed similarly; therefore, treatment selection should prioritize tolerability, manageability, drug-drug interactions, and patient preferences.

The integration of CDK4/6 inhibitors into anti-HER2 treatment strategies represents a promising approach to address the unique biology of HR + /HER2 + BC. Molecular profiling and personalized treatment strategies are essential to optimize patient outcomes and reduce unnecessary toxicity.