Abstract PS1-11-15: Current and future use of oral selective estrogen receptor degraders (SERDs) in the management of ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A survey of 20 breast cancer research leaders (RLs)

Abstract Background: The Jan 2023 approval of elacestrant (E) for patients with ER+ HER2-neg mBC and an ESR1 mutation (ESR1mut) with disease progression (PD) on endocrine therapy introduced new considerations for biomarker-guided decision-making. In the past year (y), 2 seminal phase III trials (EMBER-3, SERENA-6) reported potentially practice-changing findings with novel SERD-based strategies. We sought to determine the current and potential use of these agents. Methods: In Sep 2025, 20 US and international RLs completed a case-based survey on the management of ER+ HER2-neg ESR1mut mBC. For each case, a number of clinical factors (age, site/extent of metastases, symptom burden, duration of benefit with first-line treatment, PIK3CA mutations) were varied. A modest honorarium was offered. Results: All RLs employ ESR1mut testing, with 7 first doing so at metastatic diagnosis, 10 at PD on first-line treatment and the rest customizing their approach. 12 favor circulating tumor DNA and 8 have no preference between tissue and liquid ESR1 assays. For a 65-y-old patient with ESR1mut disease, PD 2.5 y after first-line CDK4/6 inhibitor (CDKi)/aromatase inhibitor (AI), and minimally symptomatic bone mets, 16 of 20 RLs recommend E. For the same patient with symptomatic visceral mets, only 4 would deploy the oral SERD. For the same patient but with coexisting PIK3CA mutations, E was preferred by 12 RLs in cases with bone-only mets but only by 3 for symptomatic visceral disease (Table). Other factors, including age and shorter duration on CDKi/AI, affected treatment preferences across various situations, with somewhat more RLs turning to E for an 80-y-old and fewer for a 65-y-old with PD after 10 mo of first-line treatment. Half of the RLs view select other SERDs as equivalent to E in efficacy and tolerability and 17 of 20 consider imlunestrant clinically equivalent whenever E is employed. All would use imlunestrant with abemaciclib in select situations. Regarding serial monitoring for ESR1mut during first-line treatment and early switching to a SERD (camizestrant) for patients with “molecular progression” (as in SERENA-6), 13 RLs believe more data are required but 7 endorse this approach now. Conclusions: RLs have rapidly incorporated E into the management of progressive ER+ HER2-neg ESR1mut mBC, but the decision to employ this agent appears to be heavily influenced by the global disease burden and the duration of benefit from first-line treatment. Most RLs consider the newly approved imlunestrant largely equivalent to E, and all would also consider its use in combination with abemaciclib in certain situations. Many fewer would use camizestrant for patients found to have an ESR1mut without clinical PD, but an important and significant minority believe this option should be available to select patients. Citation Format: K. H. Pang, K. A. Ziel, D. Paley, S. A. Wander, M. R. Lloyd, N. Love. Current and future use of oral selective estrogen receptor degraders (SERDs) in the management of ER-positive (ER+), HER2-negative (HER2-neg) metastatic breast cancer (mBC): A survey of 20 breast cancer research leaders (RLs) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-11-15.