ESR1 mutation

RWE confirms the effectiveness and safety of multiple recently approved oncology drugs reinforcing the external validity of RCTs.

P2, N=100, Completed, Sermonix Pharmaceuticals Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> May 2025 | Trial primary completion date: Dec 2024 --> May 2025

P2, N=297, Recruiting, Kristina A. Fanucci | Trial completion date: Oct 2029 --> Oct 2030 | Trial primary completion date: Dec 2028 --> Dec 2029

bESR1 was detected prior to clinical progression in half of patients. Our study suggests the benefit of bESR1 monitoring during palliative endocrine therapy.

P2, N=297, Recruiting, Kristina A. Fanucci | Not yet recruiting --> Recruiting

ESR1 alterations were most frequent in HR + /HER2- BC samples and missense mutations were more frequent in metastatic samples, consistent with their role in ET resistance and disease progression. ESR1 alterations co-occurred with therapeutically relevant alterations in other genes that may help inform clinical decision-making. Gynecologic tumors harbored ESR1 alterations that have prognostic and potentially therapeutic relevance.

Novel oral SERDs may represent a paradigm shift in managing PD after 1 L therapy, showing potential to improve PFS in selected patients.

Mutational analysis and molecular docking identified potential metal interaction sites within ESRRB's ligand-binding domain. Together, these results suggest calcium acts as a natural ligand for ESRRB and cadmium, which mimics calcium, activate ESRRB to mediate cell stemness and pluripotency.

Increased cancer risk, insulin resistance, and infertility all originate from defective estrogen signaling.

Giredestrant and camizestrant induced significant bradycardia in wild-type zebrafish embryos, whereas fulvestrant and amcenestrant (SERDs that do not induce bradycardia in patients) did not alter heart rate. Mutations in gper, esr2a, and esr2b did not confer resistance to SERD-induced bradycardia, whereas esr1 mutant embryos were protected. These findings demonstrate that SERD-associated bradycardia is mediated through Esr1 signaling, supporting an on-target adverse effect.

ESR1 mutations, while rare overall in treatment-naïve EC, are more prevalent in NSMP LGEC, potentially affecting AI efficacy. ESR1 status should be considered in selecting hormonotherapy and as a stratification factor in AI trials.