Real-world study of clinical and genomic factors associated with elacestrant outcomes in ESR1-mutant metastatic breast cancer

ESR1 mutations mediate resistance to antiestrogen therapy in HR-positive metastatic breast cancer (mBC). Elacestrant, an oral selective estrogen receptor degrader, improves progression-free survival over standard endocrine therapy in ESR1-mutant mBC. A retrospective study using the GuardantINFORM database assessed real-world elacestrant use and clinical-genomic factors associated with outcomes. The study included 756 patients with activating ESR1 mutation detected < 6 months before elacestrant initiation (January 2023-March 2024), with 76% after prior CDK4/6 inhibitors and 38% after prior chemotherapy. Median time-to-next-treatment was 6.4 months, and median time-to-treatment-discontinuations was 4.6 months. Higher ESR1 polyclonality (≥ 4 alterations; 11% of patients) correlated with shorter TTNT of 5.2 months. Disease with dual ESR1 and PI3K pathway mutations (PIK3CA, AKT1, PTEN) had a median TTNT of 5.2 months. The authors conclude that in ESR1-mutant mBC, elacestrant treatment durations support the routine use of elacestrant monotherapy in appropriately selected patients.