Integrating ESR1 Testing Into Treatment Planning for HR+/HER2- Metastatic Breast Cancer

ESR1 Mutation Testing and Treatment Strategy

ESR1 mutations emerge as resistance mechanisms after first-line endocrine therapy combined with CDK4/6 inhibitors in hormone receptor (HR)–positive breast cancer patients. These mutations should be tested after every disease progression since targeted therapies are now available to address this specific resistance pathway. The oncologist emphasizes checking for ESR1 mutations at each treatment transition from first-line to second-line therapy and beyond.

Liquid biopsies are the preferred testing method over tissue biopsies for ESR1 mutation detection. While tissue biopsies only sample a single tumor location, liquid biopsies provide a comprehensive snapshot of all metastatic lesions simultaneously, increasing the likelihood of detecting mutations that may be present in some locations but not others. This approach offers a more complete picture of the tumor’s molecular landscape.

Currently, elacestrant is the only approved oral selective estrogen receptor degrader (SERD) specifically targeting ESR1 mutations in HR-positive, HER2-negative metastatic breast cancer. The medication is included in NCCN guidelines for patients with these mutations. Previous treatments showed limited efficacy against ESR1 mutations, making elacestrant’s targeted approach particularly valuable for this specific resistance mechanism.