HER-2 positive

The study results confirm the reproducibility of HER2 status assessment using a unified diagnostic approach in a multicenter setting. The application of standardized HER2 interpretation criteria ensures data comparability and provides a methodological basis for further clinicopathological studies and for the implementation of HER2-targeted therapeutic strategies in clinical practice.

The temporal relationship between molecular and radiologic findings observed here suggests potential value for earlier detection of disease activity, although whether such lead time translates into improved clinical outcomes requires prospective validation. The findings support prospective evaluation of this approach, including the ongoing TROPHY trial investigating this therapeutic approach.

The approval of T-DXd for HER2-positive (IHC3+) CRC marks ADCs' entry into this treatment arena...This review focuses on the clinical performance of ADCs and explores design considerations and future directions for ADCs in CRC. This study provides a reference for researchers to understand and learn ADC.

Phenotype-specific therapies are incorporated through simple pharmacodynamic surrogates: Paclitaxel chemotherapy acting primarily on HER2+ cells and Notch-pathway inhibition targeting HER2- cells...In contrast, simultaneous initiation suppresses both phenotypes more effectively and avoids strong rebound. These findings highlight the importance of ecological structure in therapy design and support simultaneous combination therapy followed by targeted maintenance.

Neoadjuvant dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy represents the current standard-of-care for HER2-positive breast cancer. Importantly, Xenium in situ profiling further revealed biological correlates underlying model predictions, including HER2-enriched tumor cell aggregation and neutrophil-helper T-cell interactions, thereby highlighting the mechanistic interpretability of the model. Collectively, HER2-LADDER unites digital pathology and high-resolution spatial profiling into a clinically accessible AI framework, offering a robust, transparent, and biologically grounded tool to tailor individualized HER2-targeted therapy optimization.

P1, N=28, Suspended, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Suspended | Trial primary completion date: Apr 2026 --> Aug 2026

P2, N=43, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

In a multivariate regression analysis the cumulative dose of anthracycline (OR = 1.01, 95% CI: 1.00-1.01, p = 0.002) and LVEF at baseline (OR = 0.83, 95% CI: 0.70-0.99, p = 0.0344) were independent predictors of a cardiotoxic effect. Trastuzumab-related cardiotoxicity resulting in early treatment discontinuation negatively influences DFS, but does not seem to influence OS.

HER2-low status was associated with worse OS in breast cancer patients with certain negative prognostic factors compared with HER2-zero status. Additionally, HER2-low1+ and HER2-low2+/ISH(-) subgroups predominantly exhibited HR+ status.

Obesity was associated with lower ORR with letrozole alone, whereas this association was not observed in patients treated with taselisib.

MRI-guided shorter neoadjuvant chemotherapy duration is associated with less pronounced declines and better long-term preservation of HRQOL in patients with early HER2-positive breast cancer. These findings support MRI-guided treatment de-escalation as a strategy to reduce survivorship burden without compromising efficacy.

Postoperatively, he received adjuvant stereotactic radiosurgery (30-35 Gy in five fractions) to the resection cavity and was transitioned from tamoxifen to trastuzumab deruxtecan (T-DXd) for improved CNS-directed systemic therapy. Surveillance imaging at 6 months demonstrated no intracranial recurrence, and systemic restaging showed no extracranial disease progression. This case highlights the importance of prompt neuroimaging for new neurological symptoms in male breast cancer patients and supports a multimodal strategy, including surgical resection, focal radiation, and CNS-penetrant HER2-targeted therapy, for achieving durable intracranial control in select patients with isolated brain metastasis.