Abstract Purpose: The EMERALD trial led to the approval of elacestrant for estrogen receptor (ER)–positive, HER2-negative, estrogen receptor 1 (ESR1)–mutated advanced or metastatic breast cancer (mBC) with disease progression following at least one line of endocrine therapy (ET). Subgroup analyses provided evidence suggesting that elacestrant enables ET sequencing in the second line before other targeted combinations, which could delay chemotherapy-based regimens. Experimental Design: This study used claims data from the Komodo Research Dataset linked with Foundation Medicine Inc. clinical genomic data from patients with estrogen receptor+/HER2− mBC harboring an ESR1 mutation treated with elacestrant. The primary outcome measure was time to next treatment (TTNT). Results: Among 306 patients, 93.8% had prior ET ± cyclin-dependent kinase 4/6 inhibitor for ≥12 months, 50.0% had prior chemotherapy, and 72.2% had prior fulvestrant. Median TTNT (mTTNT) was 8.2 months [95% confidence interval (CI), 6.3–13.0] in patients with 1 to 2 prior lines and 7.5 months (95% CI, 7.1–9.9) in those with ≥3 prior lines of ET. In patients with coexisting ESR1- and PI3K-pathway–mutated tumors, mTTNT was 6.3 months (95% CI, 4.8–7.9). mTTNT was 7.9 months (95% CI, 7.1–9.8) in all patients and was also sustained in patients with no prior fulvestrant [12.9 months (95% CI, 7.2–not reached)], no prior chemotherapy [8.4 months (95% CI, 7.1–13.3)], visceral metastasis [7.9 months (95% CI, 7.0–9.9)], and liver metastases [7.2 months (95% CI, 6.3–9.0)]. Conclusions: Elacestrant demonstrated a durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody–drug conjugates, or targeted combinations. See related article by Lloyd et al., p. 169