HER-2 negative

This integrative analysis characterized the ribociclib pharmacokinetic and exposure-QTcF relationship, revealed the population effect on both pharmacokinetic and QTcF response, and justified the 400-mg dose in EBC. This work illustrates the utility and impact of quantitative pharmacology in justifying different doses across different patient populations for oncology therapies.

In our randomised, Intermediate RS cohort treated with chemotherapy we observe an association between higher stromal tumour-infiltrating CD8+ lymphocyte (sTIL CD8+) density and poor outcome (ΔLR-χ2: 6.79, p = 0.009), which we validate using data from whole-resection specimens (ΔLR-χ2: 8.90, p = 0.003). Our data thus provide insights into the immune states in ER+HER2- breast cancer, and propose sTIL CD8+ density as candidate biomarker for treatment decisions.

The incidence of anemia (43.9% versus 28.3%, p = 0.01), ≥grade 3 anemia (9.8% versus 1.9%, p = 3.10E-03), ≥grade 3 thrombocytopenia (9.8% versus 1.9%, p = 3.10E-03), ≥grade 3 ALT (6.1% versus 0.4%, p = 3.10E-03) and AST (7.3% versus 1.9%, p = 0.02) dysfunction occurred more frequently in the high-altitude group. Patients with HR+/HER2- ABC in the high-altitude region experienced inferior survival outcomes and individualized tolerability to CDK4/6i, which may inform scientific research and the management of CDK4/6i in Chinese patients with HR+/HER2- ABC.

P2, N=27, Recruiting, Xijing Hospital | Trial primary completion date: Apr 2026 --> Dec 2026

P2, N=13, Recruiting, University of Wisconsin, Madison | Trial completion date: Jun 2026 --> Jul 2027 | Trial primary completion date: Jun 2026 --> Jul 2027

P2, N=40, Recruiting, University of Illinois at Chicago | Trial completion date: May 2026 --> May 2027 | Trial primary completion date: May 2026 --> May 2027

Claudin-18 isoform 2 (CLDN18.2) has rapidly moved from a gastric-lineage surface antigen to an actionable therapeutic target in advanced gastric and gastroesophageal junction (G/GEJ) adenocarcinoma, following the SPOTLIGHT and GLOW Phase 3 trials, which established zolbetuximab plus fluoropyrimidine-platinum chemotherapy as a first-line option for patients with CLDN18.2-positive, HER2-negative disease...Collectively, current evidence supports a reassessment-based rather than assumption-based approach to CLDN18.2 sequencing. However, key gaps remain, including the optimal interface with PD-1-based first-line therapy, the geographic generalizability of several next-generation datasets, standardized retesting strategies at progression, and prospective validation of modality-specific sequencing after target modulation.

Receptor discordance between primary tumors and nodal metastases is common, with most shifts occurring within the HER2-spectrum. There was a trend toward higher RS and ER or HER2-receptor discordance. HER2 discordance was also associated with larger tumor size and larger size of nodal metastasis. As strategies emerge to target HER2-low cohorts and to include ER-low/HER2-negative disease within treatment regimens for TNBC, it may become important to consider receptor testing of nodal disease in the future.

We further discuss emerging triplet strategies and next-generation CLDN18.2-targeted platforms. Rather than considering CLDN18.2 as an isolated biomarker, we propose a treatment-oriented framework for integrating zolbetuximab into contemporary first-line management of HER2-negative advanced gastric cancer.

TYW1B mutation is associated with improved PFS and OS. However, these findings require further validation in larger cohorts.

The dataset was validated through experiments using deep learning-based segmentation models. Therefore, this dataset is a clinically relevant and first publicly available resource for the development and evaluation of automated singular nuclei segmentation and HER2 grading methods in digital pathology.