HER-2 underexpression

Integrating the clinical experience of Chinese pathologists and oncologists, and following expert panel discussions, a consensus on the clinical diagnosis and treatment of HER-2-low and HER-2-ultralow breast cancer was developed. This consensus aims to deepen clinicians' understanding of HER-2-low and HER-2-ultralow breast cancer, promote more precise clinical decision-making, and ultimately improve patient survival and quality of life.

P2, N=249, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Our findings suggest that BCNST-MP tumors are rarely larger than 5 cm and are frequently lymph node-negative. Most patients were negative for ER, PR, AR, and HER2. Notably, HER2-low expression was observed in approximately 30% of cases, suggesting therapeutic implications.

This case highlights the potential efficacy and tolerability of T-DXd in men and challenges the systematic exclusion of male patients from clinical trials involving HER2-low mBC. We advocate routine HER2-low testing and gender-inclusive trial design.

Class-wise F1 scores were 75.6% for HER2-0, 82.4% for HER2-low, and 91.5% for HER2-high, indicating the challenge in distinguishing HER2-0 and HER2-low cases. This study highlights the potential of simple yet effective deep learning techniques to significantly improve accuracy and reproducibility in breast cancer classification, supporting their integration into clinical workflows for better patient outcomes.

P1, N=138, Active, not recruiting, AstraZeneca | Trial completion date: Dec 2025 --> Jun 2026

Our findings highlight triple negative HER2-low BC as a distinct subtype identifiable via standard immunohistochemistry, beyond just biomarker status. The study underscores the prognostic diversity among BC subtypes and emphasizes the importance of personalized treatment strategies.

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.