Abstract
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have transformed the treatment landscape for patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer. However, their efficacy is influenced by various clinical and biological factors, including patient age, tumor biology, and treatment-related toxicities. The aim of this study is to evaluate the impact of demographic, clinical, and tumor-related characteristics on the efficacy of CDK4/6 inhibitors in a cohort of patients with metastatic HR+/HER2- breast cancer. We conducted a retrospective cohort study analyzing the outcomes of 95 patients with metastatic ER-positive, HER2-negative breast cancer (BC) treated with CDK4/6 inhibitors (ribociclib, palbociclib, and abemaciclib) in combination with endocrine therapy. The patient demographics, tumor characteristics, and treatment regimens were examined, with a primary focus on progression-free survival (PFS), overall survival (OS), time on treatment (TOT), and the influence of clinical and biological factors. Younger patients (under 50 years) demonstrated higher tumor aggressiveness, reflected by higher Ki67 levels and histological grades, which negatively impacted their survival outcomes. Ribociclib was associated with the highest survival benefit, particularly in younger patients. Older patients (over 50 years) showed greater rates of comorbidities and toxicity, with dose reductions correlated with improved survival outcomes. This study highlights the significance of personalized treatment strategies based on patient age, comorbidities, and tumor biology. Ribociclib shows superior efficacy in younger, less comorbid patients, while palbociclib remains a viable option for older patients with higher comorbidity burdens.