HER-2 expression

The HER2 inhibitors represent different mechanisms of actions, including trastuzumab, pertuzumab, tucatinib, and lapatinib, all of which are clinically approved, as well as PEPDG278D, a recombinant human protein which was previously shown to induce the degradation of HER2 and epidermal growth factor receptor (EGFR). Despite p95HER2 expression and resistance to current HER2 inhibitors, HER2-positive BC cells and tumors are highly vulnerable to PEPDG278D-induced degradation of HER2 and EGFR. By inducing HER2 degradation, PEPDG278D eliminates p95HER2 in HER2-positive BC cells and tumors.

These findings support a model in which CS-A-bearing CSPGs on the surface of PDAC cells sequester Tmab and limit its productive engagement with HER2. Thus, enzymatic CS cleavage emerges as a glycan-editing strategy to potentiate Tmab activity in CS-A-rich tumors.

P2, N=116, Recruiting, Yonsei University | Not yet recruiting --> Recruiting

In the remaining HER2 cohort, CLDN18.2-positive patients had shorter PFS (3.2 versus 8.0 months, HR 3.40, 95% CI 1.38-8.40, P = 0.008) and OS (7.1 versus 12.9 months, HR 2.44, 95% CI 1.04-5.74, P = 0.041). CLDN18.2 positivity may attenuate the efficacy of T-DXd in HER2-positive mGC/GEJC, supporting the rationale for dual blockade of CLDN18.2 and HER2.

The habitat model exhibited better discriminatory effectiveness in identifying HER2 positive expression in young breast cancer patients, in comparison to the whole-tumor radiomics model. The integration of conventional whole-tumor radiomics features with habitat features and clinicopathological characteristics can enhance model performance.

Compared with IHC 3+ IDC, IHC 2+/FISH+ IDC demonstrated lower pCR rates and inferior RFS in hormone receptor-negative subset following neoadjuvant trastuzumab/ pertuzumab-containing therapy. Pathologic response correlated inversely with HER2/CEP17 ratio and HER2 copy number. Reassessment of HER2 expression with more sensitive quantitative methods, particularly in IHC 2+/FISH+ tumors, may improve therapeutic stratification.

P3, N=480, Recruiting, BioNTech SE

NECTIN-4 expression differs by tissue type, limiting prognostic value and supporting site-specific biomarker assessment in BC.

Although gene amplification is rare, protein expression is more frequent, suggesting potential for targeted therapy. Detailed molecular profiling and innovative research methods are essential to further explore the therapeutic potential of HER2 in these rare cancers.

The TCHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab) demonstrated efficacy in clinical trials; however, real-world evidence remains limited. A median of three ER visits per patient was recorded, with hospitalization required in 42 patients, primarily for neutropenic fever and diarrhea. In this real‑world cohort, TCHP achieved a moderate pCR rate (45.5%), lower than clinical trial reports, with HER2 IHC 3+ and ER/PR‑negative status predicting response, but substantial toxicity-including frequent emergency visits and hospitalization, highlighting the need for improved patient selection, strengthened supportive care, and consideration of de‑escalation strategies to maintain efficacy while reducing morbidity.

Given the limited sample size, these findings are hypothesis-generating. This study provides a detailed polymer-level characterization of MPs in paired human breast tissues, offering initial insights into tissue-specific distribution.