Abstract Background: Premenopausal women represent nearly 30% of patients (pts) with ER+/HER2- early breast cancer (EBC). Ovarian function suppression (OFS) in combination with tamoxifen or aromatase inhibitors improves disease-free survival but has limitations such as toxicity, suboptimal estrogen suppression, and poor adherence. Elacestrant (ELA) showed superior efficacy vs standard endocrine therapy (ET) in pretreated pts with ER+/HER2- metastatic breast cancer. Mechanistically, ELA acts as a selective ER degrader while exhibiting agonistic activity in non-breast endocrine-responsive tissues like bone, making it particularly suitable for the adjuvant setting. In the SOLTI-ELIPSE trial, 4-week preoperative ELA in ER+/HER2- EBC postmenopausal pts led to a 53% reduction in Ki67 and complete cell cycle arrest (CCCA) rate of 27%. We hypothesize that ELA may serve as an effective ET in the premenopausal EBC setting, with or without OFS. Methods: SOLTI-2104-PremiÈRe (NCT05982093) is a phase 2, non-comparative, open-label, randomized, trial assessing ELA ± triptorelin (T) in premenopausal pts with stage I-IIB ER+/HER2- EBC, age ≥35 years, cT1 cm, and Ki67 10-35% by local assessment. Pts were stratified by PAM50 subtype (Luminal A vs Non-luminal A) and randomized to ELA 345 mg daily until surgery/biopsy at D28, alone or with T 3.75 mg on days 1 and 29. The primary endpoint was CCCA at D28 (central Ki67 ≤2.7%). Secondary endpoints included CCCA by subtype, changes in central Ki67, changes in gene expression from baseline, and safety. Changes in gene expression were evaluated per arm (paired samples), with P-values corrected using false discovery rate (FDR). Estrogen levels were monitored by LC-MS/MS. Results: From SEP 2023 to MAR 2025, 49 pts were randomly assigned to receive ELA (n=23) and ELA+T (n=26). Baseline characteristics: median age 47; caucasian 92%; cT1-T2 96%, N1 6%; grade 1-2 94%; central Ki67 median 20% in the ELA arm and 16% in ELA+T. PAM50 subtypes were 75.5% Luminal A and 24.5% Luminal B. CCCA was achieved in 28.6% and 26.9% in ELA and ELA+T, arm respectively and in a higher rate in Luminal A tumors. Ki67 was significantly reduced in both arms. Both arms exhibited a shift to a less proliferative phenotype after treatment (Table 1). PAM50 Risk of Recurrence (ROR)-high/medium switched to ROR- low, and PAM50 Luminal B subtype switched to Luminal A/Normal-like. Treatment showed a toxicity profile consistent with previous data. Conclusions: This study provides the first evidence that ELA ± OFS elicits antiproliferative and molecular responses in premenopausal women with ER+/HER2- EBC. Both regimens had comparable and significant reductions in Ki67, CCCA, ROR-P scores, and proliferation gene expression. PremiÈRe trial support the potential role of ELA as a novel ET in this population, potentially sparing the need for OFS. Citation Format: M. Bellet, P. Tolosa, C. Hernando, M. Vidal, V. Ortega, M. Tapia, S. González-Santiago, P. Sánchez, Y. Fernández, M. Cruellas, M. Alva, E. Mension, M. Espinosa-Bravo, T. Cortadellas, S. Aragón, M. Gaudio, E. Sanfeliu, P. Galván, R. Olivera, G. Villacampa, M. Bergamino, N. Santos, S. Cano-Crespo, X. González-Farré, A. Prat, J. M. Ferrero-Cafiero, A. Hurtado, T. Pascual. Elacestrant alone or in combination with triptorelin in premenopausal women with ER+/HER2- early breast cancer: primary analysis from the phase 2 SOLTI-2104- PremiÈRe trial 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 PD10-01.
Bellet et al. (Tue,) studied this question.