Abstract Background: Invasive lobular carcinoma (ILC) is a distinct histological subtype of hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer, accounting for up to 15% of cases. Despite its unique clinical behavior, patients with ILC have been underrepresented in pivotal CDK4/6 inhibitor trials, and real-world data on treatment outcomes in this population remain limited. Methods: We conducted a retrospective study of patients with metastatic ILC treated with CDK4/6 inhibitors at City Clinical Hospital No. 62 (Moscow) from 2015 to 2023. Among 803 patients with HR+/HER2− metastatic breast cancer, 141 had confirmed ILC. Demographic, clinical, and treatment-related data were extracted from medical records. Survival outcomes were estimated using the Kaplan-Meier method, and comparisons between subgroups were performed using log-rank tests. Results: The median age was 60 years, and the median follow-up was 46 months. Most patients had grade 2 tumors (82.9%) and high ER expression (Allred 8 in 72.3%). At the time of CDK4/6 inhibitor initiation, 64.7% received treatment in the first line. The most frequently used agents were palbociclib (49.3%) and ribociclib (45.7%), while abemaciclib was prescribed in 5% of cases. The median overall survival (OS) in the full ILC cohort was 49 months (95% CI: 46.1-51.9). When stratified by CDK4/6 inhibitor, the median OS was 50 months for palbociclib (95% CI: 46.4-53.6), 44 months for ribociclib (95% CI: 32.9-55.1), and not reached for abemaciclib, with no statistically significant differences between groups (log-rank p=0.276). The median progression-free survival (PFS) was 30 months overall (95% CI: 22.2-37.8), with 32 months for palbociclib, 30 months for ribociclib, and 17 months for abemaciclib (p=0.156). Subgroup analyses showed no significant differences in OS by age (60 vs ≥60; p=0.620), presence of bone (p=0.316), liver (p=0.854), or lung metastases (p=0.410). The type of endocrine backbone (aromatase inhibitor, fulvestrant, or exemestane) was not associated with differences in OS (p=0.778). Patients treated in the first line had longer OS (49 months) compared to those treated after progression on prior therapies (30 months), though the difference did not reach statistical significance. Conclusions: In this real-world cohort of patients with metastatic ILC, CDK4/6 inhibitors demonstrated clinically meaningful survival outcomes consistent with previously reported results in broader HR+/HER2− populations. No significant differences in OS or PFS were observed between individual CDK4/6 inhibitors or across clinical subgroups. These findings support the use of CDK4/6 inhibitors in ILC, while highlighting the need for prospective studies to better define optimal treatment strategies in this distinct population. Citation Format: A. Danilova, P. Shilo, I. Nigmatullina, D. Stroyakovskiy. Real-world outcomes of CDK4/6 inhibitors in patients with metastatic invasive lobular carcinoma: a retrospective single-center study 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 PS2-02-21.
Danilova et al. (2026) studied this question.