Clinical Outcomes of Endocrine Therapy Plus CDK4/6 Inhibitors in Elderly Patients with HR+/HER2-Low Metastatic Breast Cancer

Clinical Outcomes of Endocrine Therapy Plus CDK4/6 Inhibitors in Elderly Patients with HR+/HER2-Low Metastatic Breast Cancer Aim: The combination of endocrine therapy (ET) and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors is the current standard treatment approach for patients with hormone receptor-positive (HR+) / human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC).However, studies specifically evaluating the efficacy of this standard treatment in elderly patients within the HER2-low subgroup, which is considered a new entity, are limited.The aim of our study was to investigate the treatment efficacy and survival data for this specific group.Methods: Patients with HR+/HER2-MBC defined as HER2-low (+1 or +2 by immunohistochemistry and negative by in situ hybridization) who were followed up between 2019 and 2023 were included in the study.The results of 92 patients over the age of 65 who received a CDK4/6 inhibitor and ET for at least 3 months were evaluated.Results: Our study evaluated 92 patients 65 years and older.Survival analyses were conducted for the HER2-low and HER2-zero groups.The median overall survival (OS) for all patients was 108 months [95% confidence interval (CI): 64-152].In the HER2-low group, the median OS was 88 months (95% CI: 22-154), whereas the median OS was not reached in the HER2-zero group (p=0.054).Although not statistically significant, the difference between the two groups is clearly observed in the Kaplan-Meier graph.Median progression-free survival (PFS) for the overall population was 27 months (95% CI: 15.9-38.1).Similarly, when mPFS was compared between the two groups, outcomes were better in the HER2-zero group, with a median of 34 months (95% CI: 28.8-39.1)versus 17 months (95% CI: 9.2-24.8),which was statistically significant (p=0.026). Conclusion:The behavior and prognosis of the HER2-low subgroup are still being investigated in recent studies.Our study indicated that the HER2low group might be associated with poorer survival outcomes and treatment resistance to CDK4/6 inhibitors and endocrine therapy in elderly MBC patients.