Abstract
Background: Although CDK4/6 inhibitors combined with endocrine therapies have improved outcomes in HR+ HER2-negative metastatic breast cancer, predictive biomarkers for treatment response and adverse effects remain limited. This study assessed the prognostic and predictive value of large unstained cells (LUC), a subset of white blood cells that may reflect immune status or treatment response. Methods: A retrospective analysis of 210 patients with HR+ HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors between 2021 and 2024 was conducted. Clinical data, including demographics, tumor characteristics, and treatment regimens, were analyzed. Based on LUC levels, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. Results: The cohort had a median age of 57, of which 78% were postmenopausal. Common metastatic sites included bone (67%) and liver (24%). At a median follow-up of 18.5 months, the PFS and OS rates were 65% and 83%. Patients with low LUC levels had significantly shorter PFS (OR: 1.91; p = 0.014) and OS (OR: 2.39; p = 0.012), while high LUC levels correlated with a lower incidence of grade 3 neutropenia (OR: 0.49; p = 0.017). Liver metastasis and prior treatments were also linked to shorter survival. Conclusions: LUC levels emerge as a promising biomarker for predicting survival outcomes and the risk of neutropenia in HR+ HER2-negative metastatic breast cancer patients treated with CDK 4/6 inhibitors and endocrine therapy, showing their potential to guide personalized treatment approaches.