Abstract PS1-08-18: The significance of HER2 Low status on clinical outcomes of breast cancer patients with metastatic hormone-receptor positive tumors treated in the CDK4/6 inhibitor era

Abstract Background: HER2-low (IHC 1+ or 2+/ISH-) is a relatively new sub-type in breast cancer (BC) classification, describing tumors without HER2-oncogene overexpression but rather lower levels of HER2. We describe the characteristics and clinical outcomes of patients with hormone-receptor positive (HR+) metastatic BC (mBC) with HER2-low and HER2 IHC 0 tumors, treated with CDK4/6 inhibitors (CDK4/6i) prior to inclusion of trastuzumab-deruxtecan in the national formulary, in a 2.8-million-member Health Maintenance Organization (HMO). Methods: Patients aged =18 years who initiated endocrine treatment with-CDK4/6i combination between 1st January 2018 to 31st December 2022 for mBC were identified in this retrospective cohort study with follow up until 31st December 2023. Patients were classified into HER2 IHC 0 and HER2-low, based on deidentified data extraction. Kaplan-Meier analysis was used to describe time-on-treatment (TOT, as a surrogate for progression-free-survival) and overall survival (OS). Results: A total of 1,067 patients were identified with a median age of 63 years, 60.7% were HER2-low, 31.4% were HER2 IHC 0 and 7.9% with missing data A total of 705 patients received first-line CDK4/6i with an aromatase inhibitor (AI) and 362 received CDK4/6i with fulvestrant (F). Median follow-up periods were 27.6 months and 23.0 months, respectively. For the group of patients receiving first-line CDK4/6i 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-08-18.