In this review, we discuss mechanisms of resistance and dissemination of ESR1 mutations, as well as detection methods for ESR1 mutation tracking, newly discovered potential therapeutic targets, and the clinical implications and treatment options for treating patients with ESR1 mutant-bearing tumors.

Aug 15, 2021 · In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to the backbone of therapy, estrogen deprivation by aromatase inhibition. How these mutations affect tumor sensitivity to established and novel therapies are active areas of research.

23 hours ago · Phase III VERITAC-2 trial results show vepdegestrant significantly improved progression-free survivalcompared to fulvestrant in patients with ESR1-mutant (ESR1m) advanced or metastatic breast cancer, but did not achieve statistical significance in the overall intent-to-treat population.

May 17, 2023 · To aid in treatment selection, the Expert Panel recommends routine testing for emergence of ESR1 mutations at recurrence or progression on ET (given with or without CDK4/6 inhibitor) in patients with ER-positive, HER2-negative MBC.

One major driver of ET resistance is mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly detrimental in metastatic breast cancer (MBC) as they are present in as high as 36% of the patients.

ESR1, the gene that encodes the estrogen receptor (ER), is known to undergo ligand-binding domain (LBD) mutations, gene amplification, or an ESR1/YAP1 translocation that are potential mechanisms of resistance to ET (1, 2).

ESR1 mutations emerge while on treatment (typically AI) and are not usually detected before treatment. 1,7,8 ESR1 mutations are best detected by blood-based, circulating-tumor DNA analyses, which have greater sensitivity and are less invasive than tissue-based testing. 1,7-9.

Nov 1, 2019 · In this review, we discuss the mechanisms of resistance and dissemination of ESR1 mutations as well as the detection methods for ESR1 mutation tracking, newly discovered potential therapeutic targets, and the clinical implications and treatment options for treating patients with ESR1 mutant-bearing tumors.

Aug 14, 2019 · Mutations in the ESR1 gene (ESR1m) are important mechanisms of resistance to endocrine therapy in estrogen receptor-positive advanced breast cancer and have been recognized as a prognostic and predictive biomarker as well as a potential therapeutic target.

Apr 17, 2018 · A recent publication by Toy et al. analyzed the spectrum of ESR1m from over 900 patients. Seventy-eight ESR1m were detected in 10%, with D538G being the most frequent (36%), followed by Y537S (14%). A variety of novel-activating mutations were also identified (e.g., Y537D, V422del, L469V).