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 …

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.

3 days ago · Vepdegestrant is the first PROTAC degrader to demonstrate clinical benefit in a Phase 3 trial, supporting its potential as a first-in-class therapy for ESR1m metastatic breast cancer. Given the high prevalence of ESR1 mutations (~40% of second-line cases) and the limited treatment options post-CDK4/6 inhibitor therapy, these findings highlight ...

2 days ago · Data from the phase 3 VERITAC-2 trial (NCT05654623) revealed that the prespecified target HR for PFS of 0.60 was exceeded in the ESR1m population. Additionally, the trial did not reach statistical significance in PFS improvement with vepdegestrant vs fulvestrant in the intent-to-treat population.

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.

2 days ago · In the ESR1m population, treatment with vepdegestrant resulted in a statistically significant and clinically meaningful improvement in PFS compared with fulvestrant. Topline results were announced ...

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.

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.

3 days ago · The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach ...

3 days ago · The primary endpoint was progression-free survival (PFS) in the intent-to-treat and ESR1m populations as determined by blinded independent central review. Overall survival is a key secondary endpoint.