HR positive + HER-2 negative

Simulations suggested that Dato-DXd at 6 mg/kg Q3W provide superior tumor control and improved PFS compared to a lower dose in patients with HR+/HER2- BC. This work underscores the importance of integrating advanced modeling techniques into the dose optimization paradigm.

Prognostic stage significantly influences survival among patients with low RS. RS < 11 alone should not automatically downstage patients to PPS IA; anatomic and other nongenomic factors remain important for prognosis.

P=N/A, N=12, Not yet recruiting, University of Vermont Medical Center

In HR+/HER2- breast cancer, tumors with lower HER2 mRNA expression exhibit higher lymphocytic infiltration, suggesting the presence of a distinct immunologically active subset. Oncotype DX single gene scores, particularly HER2, may provide information beyond recurrence risk prediction and help identify patients who may benefit from immune-modulating therapeutic strategies.

Baseline TKa provides prognostic information, with potential added value from repeated testing in those with high baseline levels. TKa behaves as a continuous biomarker of risk, and continuous modelling may offer more clinically informative individual risk estimation, while thresholds may retain value for specific clinical contexts. Validation in larger cohorts is warranted to support integration into routine practice.

P3, N=331, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

This consensus uniquely contextualizes global evidence for GCC-specific healthcare constraints, addressing gaps in diagnostic access, affordability, and real-world feasibility, while providing treatment recommendations that help clinicians refine therapeutic strategies and incorporate patient preferences for improved outcomes. The panel recommends early genomic testing (PIK3CA, AKT, BRCA, ESR1) to guide therapy, prioritizing targeted agents such as oral SERDs and PI3K/AKT inhibitors in second-line sequencing, cautious use of alpelisib in diabetic patients, and incorporating patient preferences through shared decision-making and multidisciplinary care.

ctDNA-based methylation and fragmentomic profiling revealed exploratory, treatment specific molecular dynamics, highlighting biological differences between CDK4/6 inhibitors. These findings support the feasibility of liquid biopsy-based biomarker studies in this setting, although their potential clinical relevance remains preliminary and requires validation in larger cohorts with earlier and more granular on-treatment timepoints.

Palbociclib, ribociclib, and abemaciclib are approved for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (aBC), in combination with aromatase inhibitors or fulvestrant...Subsequent therapies, including chemotherapy (CT), endocrine therapy (ET) with or without everolimus, and CDK4/6i-based regimens, were evaluated...These findings emphasize the variability in treatment efficacy following CDK4/6i therapy and underscore the importance of personalized treatment strategies. Further research is needed to optimize therapeutic sequences and improve patient outcomes in this setting.

The study highlights SG's clinical relevance and the challenge of translating trial efficacy into real-world outcomes, reinforcing the need for further investigation of tolerability in broader populations.

P=N/A, N=240, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting | Trial completion date: Jul 2029 --> Dec 2029 | Initiation date: Jul 2025 --> Jan 2026 | Trial primary completion date: Jul 2029 --> Dec 2029