HER-2 negative + HR positive + ESR1 mutation

These results demonstrate that both dPCR and NGS-based liquid biopsy workflows can be successfully implemented for ESR1 mutation testing in routine clinical practice using locally validated assays. This multicentre verification study provides practical guidance on assay verification, DNA input requirements, and key analytical parameters required to ensure reliable ESR1 mutation detection across different European laboratories. Robust analytical verification of ESR1 testing may improve diagnostic reliability and support personalized treatment strategies for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.

Oral SERDs are reshaping the management of ESR1-mutant disease, with agents such as elacestrant and imlunestrant emerging as standard second-line options. However, primary resistance to SERD monotherapy remains substantial, highlighting the need for combination strategies. Future directions include ctDNA-guided approaches and expansion into earlier treatment settings.

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

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.

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

Our findings suggest a unique genomic and immunologic landscape in MaBC requiring a sex-informed approach and provide candidate therapeutic targets and mechanisms of resistance.

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

With the growing integration of liquid biopsy technologies and molecular monitoring into clinical practice, dynamic treatment adaptation guided by real time molecular profiling is expected to refine therapy selection. Elacestrant is a benchmark in the shift toward individualized endocrine therapy in metastatic breast cancer, bridging molecular precision with clinical practicality.

Patients with metastatic HR+HER2- IBC demonstrated a shorter time on treatment suggesting shorter duration of response on CDKI + HT, which is markedly inferior to reported data for non-IBC patients from phase III trials.

This review outlines the key challenges to validating and implementing ctDNA-guided early endocrine switching in routine clinical practice and discusses its potential to reshape monitoring and decision-making in metastatic hormone receptor-positive, HER2-negative breast cancer.

qPCR, dPCR, and NGS assays can detect common ESR1m with differing sensitivity and specificity depending on the assay and amount of input DNA. Assay selection will vary depending on analytical performance, turnaround times, lab infrastructure and expertise, healthcare setting, and regional variation in market costs.