Progression Patterns as Determinants of Post-Progression Survival in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Treated with Cyclin-Dependent Kinase 4/6 Inhibitors

Abstract

Objective: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved outcomes in hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2−) metastatic breast cancer; however, most patients eventually develop disease progression. The clinical significance of progression patterns in this setting remains poorly defined. Methods: This retrospective single-center study included patients with HR+/HER2− metastatic breast cancer who developed progression during first-line CDK4/6 inhibitor therapy. Progression patterns were categorized according to newly developed metastatic sites, including visceral, liver-specific, bone-only, and multisite progression. Post-progression survival (PPS) was evaluated using Kaplan–Meier analysis and Cox regression models. Results: A total of 87 patients were included. At progression, 86.2% developed new metastatic lesions, with new visceral progression observed in 56.3% and new liver metastases in 35.6%. In multivariable analysis, new visceral progression was independently associated with worse PPS (hazard ratio [HR], 2.93; 95% CI, 1.48-5.82; P = .002), as was new liver metastasis (HR, 3.41; 95% CI, 1.79-6.50; P < .001). Patients with new visceral progression had significantly shorter median PPS compared to those without (8.4 vs. 16.5 months), and similar findings were observed for liver involvement (8.0 vs. 15.8 months). Multisite progression showed a trend toward inferior survival, whereas bone-only progression was not associated with worse outcomes. Conclusion: In patients with HR+/HER2− metastatic breast cancer, the site of first progression after CDK4/6 inhibitor therapy may help estimate subsequent prognosis. New visceral disease, especially liver involvement, was linked to shorter PPS, whereas bone-only progression followed a less aggressive course. These routinely available imaging findings may add practical value when assessing risk after CDK4/6 inhibitor failure.   Cite this article as: Aliyev V, Birsin Z, Günaltılı M, et al. Progression patterns as determinants of post-progression survival in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer treated with cyclin-dependent kinase 4/6 inhibitors. Cerrahpaşa Med J. 2026, 50, 0061, doi: 10.5152/cjm.2026.26061