ESR1 mutation

P1/2, N=305, Recruiting, Salubris Biotherapeutics Inc. | N=210 --> 305

Imlunestrant monotherapy had a similar safety profile between patients aged <65 and ≥65 years, while imlunestrant + abemaciclib had a similar safety profile to other abemaciclib+ET combinations in both age groups. Imlunestrant and imlunestrant + abemaciclib provide effective, convenient oral therapy with a favorable and manageable safety profile for patients with ER+, HER2- ABC with recurrence/progression on/after ET.

P3, N=315, Active, not recruiting, AstraZeneca | Trial completion date: Nov 2027 --> Sep 2028

Pooled randomized evidence supports a clinically meaningful benefit of oral SERDs over standard ET after endocrine progression in HR + /HER2-ABC, with the strongest and most consistent efficacy observed in ESR1-mutated disease.

GHS/QoL and function were maintained across treatment arms, despite a higher incidence of diarrhea in the imlunestrant-abemaciclib group. These PRO findings complement the efficacy and safety results from EMBER-3 and further support the favorable risk-benefit profile of imlunestrant, either as oral monotherapy or in combination with abemaciclib, in patients with advanced breast cancer.

P1/2, N=65, Recruiting, Sarah Sammons, MD | Not yet recruiting --> Recruiting | Initiation date: Mar 2026 --> Nov 2025

This switch-blocker-enhanced pyrosequencing assay presents a targeted, multiplexed, and accessible approach for detecting ESR1 hotspot mutations in liquid biopsies. This assay has potential for dynamic monitoring of therapeutic resistance, facilitating timely treatment decisions in advanced breast cancer management.

Moreover, we identified PR-dependent transcriptional programs such as the unfolded protein response (UPR) that can be leveraged to target CSCs in Y537S ESR1-mutant breast cancer. Our findings demonstrate an interplay between PR and mutant ER function and provide insight into PR-driven pathways that can be exploited as potential therapeutic avenues in ER+ breast cancer.

Off-the-shelf general-purpose LLMs in a fixed retrieval pipeline were able to abstract a range of variables from complex longitudinal oncology records with performance approaching inter-oncologist variability for key tasks, without any fine-tuning or institution-specific retraining. This approach offers a practical path to scaling the creation of research-grade retrospective datasets from narrative medical records.

P3, N=256, Active, not recruiting, Laekna Limited | Recruiting --> Active, not recruiting

Our findings demonstrate that integrating baseline ctDNA-derived TFx metrics with established clinical variables significantly improves risk stratification in HR-positive/HER2-negative ABC.