HER-2 underexpression

Similarly, in the external validation set, T2 values showed moderate diagnostic efficacy, with AUCs of 0.837, 0.808 and 0.835 for the respective comparisons. T2 quantification derived from SyMRI shows promise as a noninvasive biomarker for identifying HER2-low-expressing breast cancer, supporting its potential role in guiding individualized treatment strategies.

HER2 heterogeneity is present in both primary breast cancer and liver metastases. Ongoing monitoring of molecular markers, particularly HER2 expression, remains essential for breast cancer patients, as it may provide opportunities for therapeutic intervention.

Antibody-drug conjugates (ADCs), particularly trastuzumab deruxtecan (T-DXd), have markedly improved survival and also exert antitumor effects through immune activation...Tumor vaccines and genomics-driven targeted drugs, such as trastuzumab-α-amanitin conjugates, hold promise in reactivating antitumor immunity. This review summarizes current progress in immunotherapy for HER2 low-expressing TNBC, with emphasis on ADCs, combination regimens, and emerging precision strategies, aiming to inform future research and clinical application.

These issues include the heterogeneity of HER2 protein and gene expression, reporting of HER2-ultralow, testing and interpretation issues of HER2 low-level expression, the establishment of external controls for HER2 testing, the interpretation standards for rare staining patterns, and the role of new technologies in HER2-low expression testing. These findings reflect the effectiveness and challenges in the implementation of the guidelines and provide valuable insights for the further optimization of the HER2 testing guidelines in the future.

Trastuzumab-based therapy has shown survival benefit in HER2-positive SEC, leading to its inclusion in current treatment guidelines...The prognostic value remains debated, though recent trials of antibody-drug conjugates (e.g., T-DXd) show promise...Diagnostic challenges include variable scoring systems, intratumoral heterogeneity, and HER2-low classification. Standardization of testing criteria and further clinical validation of HER2-targeted strategies across gynecologic tumors are essential to guide personalized therapy and improve outcomes.

Results from a recent Phase 3 clinical trial (DESTINY-Breast04) established the efficacy of the antibody-drug conjugate, trastuzumab deruxtecan (T-DXd) in patients with metastatic breast cancer with immunohistochemistry (IHC) score 1+ or 2+ and without in situ hybridization amplification, defining a new category of metastatic breast cancer known as human epidermal growth factor receptor 2 (HER2)-low...The panel recommended robust standard operating procedures to overcome these challenges. The central point of discussion was to implement clear guidelines, careful supervision of pre-analytical and analytical issues, and specialized training for accurate HER2 testing that would help select patients eligible for novel therapies.

This is the first EQA ring study held within Vietnam for ER, PR, HER2 and Ki-67 and sets the base line as to the current level of reproducibility in the country. Continued participation in the program will help ensure the reliability of testing for clinical use.

Despite similar clinicopathological features, IHC2+/ISH- status was independently associated with lower pCR rates compared to IHC1+. These findings suggest that HER2-low subgroups may influence response to NACT and should be considered in multivariable prediction models, potentially informing stratified treatment approaches in the era of anti-HER2 ADCs.

Further subgroup analysis indicated that among HER2-low patients, whether they received first-line treatment, subsequent treatment, or were treated with Ribociclib, their prognosis was worse...In conclusion, among patients receiving CDK4/6 inhibitor combined with endocrine therapy, HER2-low status was associated with significantly shorter PFS but not with significant differences in OS or ORR. However, it is worth noting that most of these studies are retrospective and real-world studies, with limited adjustments for confounding factors, and the statistical power of testing may be insufficient.

This study applies bibliometric tools to analyze the literature on HER2-low expression breast cancer, which shows a notable upward trend and highlights the clinical significance, providing researchers with the priorities and hotspots in this crucial field.

P1, N=115, Active, not recruiting, Daiichi Sankyo | Trial completion date: Oct 2025 --> Mar 2027

P=N/A, N=1155, Recruiting, Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company | Trial primary completion date: Jun 2027 --> Sep 2028