Identifying ESR1 mutations has become increasingly important in the management of estrogen receptor-positive (ER+)/HER2-negative metastatic breast cancer, particularly as endocrine resistance develops during treatment. Although these mutations are relatively uncommon at the start of first-line therapy, their prevalence may increase with continued exposure to endocrine treatment. A recent U.S. real-world study examined ESR1 testing practices and mutation detection patterns to better understand when these molecular changes emerge and how testing is being incorporated into clinical care.
Researchers analyzed electronic health records from the Flatiron Health Research Database, examining patients diagnosed with ER+/HER2− metastatic breast cancer between 2018 and 2024. Among 7,772 patients who initiated first-line therapy, only 3% had ESR1 mutation status evaluated at baseline, while 17% underwent testing during first-line treatment. Testing became more common over time, with the proportion of patients receiving an ESR1 test result during first-line therapy increasing from 11% in 2018–2019 to 22% in 2022–2024.
The analysis also revealed notable differences in mutation detection depending on when specimens were collected. ESR1 mutations were identified in 6.7% of baseline specimens, compared with 23% of specimens collected nine to 12 months after starting first-line therapy. Positivity increased to 38% among specimens collected at 15 to 18 months and reached 40% for those collected between 18 and 24 months. These findings illustrate how ESR1 mutation detection varies throughout treatment and reinforce the importance of understanding the timing of molecular testing.
Testing methods and turnaround times were additional areas of investigation. Approximately 60% of ESR1 tests performed during first-line therapy used tissue specimens, while 40% relied on liquid biopsies. The median interval between specimen collection and result reporting was 28 days. Among patients tested during first-line treatment, the median time from treatment initiation to the first ESR1 test was 7.4 months. These observations provide insight into how molecular testing is being used in routine oncology practice and where opportunities may exist to improve testing workflows.
Overall, the study highlights the evolving role of ESR1 testing in metastatic breast cancer management. Although testing rates increased during the observation period, many patients did not have documented ESR1 testing during first-line therapy. The researchers concluded that ESR1 mutations can be detected at different points throughout treatment, underscoring the need for continued investigation into optimal testing strategies. A clearer understanding of mutation emergence and testing practices may help clinicians incorporate molecular findings into individualized treatment planning.
Source: Meisel J, et al. Real-world estrogen receptor alpha 1 (ESR1) testing patterns and results for ER+/HER2− metastatic breast cancer in the United States, 2018–2024. PMID: 42714697. PubMed Central.