Monitoring ESR1 ctDNA During First-Line Care of HR-Positive Advanced Breast Cancer: A New Approach Authors: François-Clément Bidard, MD, PhD; Nicola Fusco, MD, PhD

https://www.medscape.org/viewarticle/1002782?sso=true&uac=148436CN&src=mkmcmr_reeng_recap_mscpedu_activity Monitoring ESR1 ctDNA During First-Line Care of HR-Positive Advanced Breast Cancer: A New Approach Below are some key learning points to help reinforce the impact of this activity. ☑ ESR1 mutations • Are rare in untreated HR+ advanced/metastatic breast cancer and mostly arise under the pressure of therapy with aromatase inhibitors • They can be characterized by interpatient heterogeneity (different mutations arise in different patients), as well as intrapatient heterogeneity (different mutations arise in different metastatic sites) • These types of heterogeneities make ctDNA assessment as a superior method compared with solid biopsy samples ☑ Currently, ESR1 mutations are assessed on progression following first-line therapy in patients with HR+ advanced/metastatic breast cancer, and if detected, are targeted by treatment • However, ESR1 mutations can arise prior to detection of clinical progression • An emerging paradigm proposes monitoring for ESR1 mutations during first-line therapy, and if detected prior to clinical progression, therapy should be changed to a different regimen • Data supporting this approach are based on the positive results from PADA-1 (switch from exemestane + palbociclib to fulvestrant + palbociclib) and SERENA-6 (switch from an aromatase inhibitor + CDK4/6 inhibition to camizestrant + CDK4/6 inhibition), both of which showed significantly improved PFS following the switch compared to continuation regimen ☑ Practical considerations for ESR1 mutation monitoring: • Using ctDNA has several advantages: noninvasive sampling, potential for serial testing, captures tumor heterogeneity, potential for real-time monitoring • Only ddPCR and NGS offer the required sensitivity • The optimal moment for starting ESR1 monitoring and interval between tests during first-line therapy has not been established: clinical trials used 2-3 months, but perhaps a more relaxed interval can be employed • Standardization of laboratory and assessment protocols will be needed for practical implementation • However, the new monitoring paradigm can add additional testing burden as well as increased costs ☑ Multidisciplinary team education is needed for practical implementation of ESR1 mutation monitoring • Medical oncologist: need to understand when to test and what to do with the results • Pathologists and laboratory staff require training for testing methods and utility of results • Nurses are involved in sample collection and patient education