HER-2 positive

For more advanced BC, care costs rise substantially, mainly due to systemic therapies and hospital-based care. The HER status at cancer presentation significantly impacts care costs across all cancer stages.

The HER2CLIMB trial demonstrated the benefit of tucatinib, trastuzumab and capecitabine (TTC) in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Treatment discontinuation due to toxicity occurred in 7.4% of participants; there were no treatment-related deaths. In this national real-world cohort, TTC demonstrated clinically meaningful activity and was not associated with any new safety signals in HER2-positive ABC, including patients previously exposed to T-Dxd and those with brain metastases.

The FROC model could help identify the low Ki67 expression (≤ 5%) and prevent unnecessary chemotherapy.

Palestinian breast cancer is dominated by hormone-receptor-positive disease, but the combined HER2-positive fraction (21.8%) and triple-negative fraction (17.6%) together account for nearly two-fifths of cases - a higher burden of aggressive subtypes than is reported in most Western series. These findings underline the importance of universal IHC testing and targeted therapy access in Palestinian breast cancer care.

Data suggest that the Fab-ageritin IT and the individual purified components preserve the toxin and Fab' activity but show enhanced cell toxicity, thus resulting in a structurally well-defined, target-specific new type of immunotoxin. The scheme outlined for its preparation is easily extendable to other therapeutic IgG1 thus providing a significant contribution to the ongoing effort to explore new combinations of payloads and targeting platforms for next-generation immunotoxins.

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