HER-2 underexpression

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

Combining with key clinical issues, this article further interprets the key points of the Expert Consensus and proposes that precise HER2 testing should focus on spatiotemporal heterogeneity, and clarify the definitions and testing standards for low expression and ultra-low expression; it also summarizes clinical key points according to different stages, and puts forward that for neoadjuvant therapy, the trastuzumab combined with pertuzumab regimen is preferred, and specific regimens should be selected according to patient characteristics, and adjuvant strategies should be formulated based on pathological complete response status; in adjuvant therapy, dual-targeted therapy is the standard regimen for high-risk patients, while low-risk and special populations require individualized selection; the treatment of relapsed and metastatic breast cancer should be formulated according to the degree of trastuzumab sensitivity, trastuzumab treatment failure, and characteristics of special populations; populations with HER2 low expression/ultra-low expression can benefit from new antibody-drug conjugates, and standardized testing and treatment selection are required. In conclusion, the diagnosis and treatment of HER2-related breast cancer should be based on precise testing, combined with patients' clinical characteristics and follow the consensus recommendations, so as to achieve individualized treatment and improve prognosis.

HER2-low expression was associated with significantly improved survival compared with HER2-negative status in metastatic TNBC. These findings highlight HER2 status as a potential prognostic factor, particularly relevant in settings with limited access to novel therapies such as immunotherapy or antibody-drug conjugates.

These subsets are clinically relevant regarding treatment with the antibody-drug conjugate trastuzumab deruxtecan (T-DXd), which has shown survival benefit in patients with metastatic carcinoma with minimal HER2 protein expression that lack HER2 gene amplification by in situ hybridisation (ISH)...We emphasise standardised testing protocols, validated assays, robust internal and external controls, and focused training for pathologists. A universal structured pathology report is proposed to highlight the accurate distinction between IHC 0 (null), IHC 0+ (ultralow), and HER2-low expression.

P4, N=30, Not yet recruiting, Anyang Tumor Hospital; Anyang Tumor Hospital