Abstract PS1-08-14: Prognostic impact of estrogen receptor expression levels in HR-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors and endocrine therapy

Abstract Background: Cyclin-Dependent Kinase 4 and 6 (CDK4/6) inhibitors in combined with endocrine therapy represent the standard first-line treatment for hormone receptor (HR)-positive/Human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Recent studies suggest that the level of estrogen receptor (ER) expression may influence treatment response. This study aims to evaluate the association between ER expression levels and clinical outcomes in this population. Methods: A retrospective study was conducted on 437 HR-positive, HER2-negative MBC patients who received CDK4/6 inhibitors (palbociclib, ribociclib, or abemaciclib) in combination with endocrine therapy at Gangnam Severance Hospital and Seoul St. Mary’s Hospital in Seoul, Korea, between 2017 and 2024. Among them, 276 patients with available ER expression level data who received this regimen as first-line palliative therapy were included in this study. ER expression was assessed using tumor tissue obtained from primary sites in de novo cases and from recurrent sites in relapsed cases. ER expression levels were stratified as high (Allred score 5-8) or low (Allred score 3-4). Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier method and compared with the log-rank test. Results: Median follow-up was 33.7 months (range, 2.0–100.7), and median patient age was 54.3 years (range 28.0–91.6). Among the 276 patients, 195 (70.6%) received palbociclib, 70 (25.4%) received ribociclib, and 11 (4.0%) received abemaciclib. Based on the Allred score, 267 (96.7%) were classified into the high ER group and 9 (3.3%) into the low ER group. In addition, 120 (43.5%) had de novo stage IV disease and 156 (56.5%) had recurrent stage IV disease, of whom 82 (52.6%) were classified as endocrine-resistant and 74 (47.4%) as endocrine-sensitive. Patients with high ER expression had significantly longer PFS than those with low ER group (median PFS: 34.3 vs. 6.3 months; 95% CI: 27.6–42.0 vs 5.2–N/A; p=0.0014). Median OS was not reached in the high ER group, whereas it was 35.7 months in the low ER group (95% CI: 72.7–N/A vs 8.2–N/A; p < 0.0001). Conclusion: High ER expression was associated with improved clinical outcomes in patients with HR-positive/HER2-negative MBC treated with CDK4/6 inhibitors and endocrine therapy. Patients with low ER expression, on the other hand, may derive less benefit from CDK4/6 inhibitors-based treatment, and consideration of alternative approaches such as chemotherapy or emerging targeted therapies may be warranted in this subgroup. Although the difference was statistically significant (p<0.05), these results should be interpreted with caution due to the small sample size in the low ER group. Further studies with larger cohorts and longer follow-up are warranted to validate these findings. Citation Format: Y. Jeong, J. Lee, K. Shin, S. Bae, S. Ahn, J. Jeong, Y. Cha, J. Kim. Prognostic impact of estrogen receptor expression levels in HR-positive, HER2-negative metastatic breast cancer treated with CDK4/6 inhibitors and endocrine therapy [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 PS1-08-14.