Predictive and prognostic value of ¹⁸F-FES PET/CT for patients with recurrent or metastatic breast cancer treated with endocrine therapy plus cyclin-dependent kinase 4/6 inhibitors

Purpose: Estrogen receptor (ER) expression and heterogeneity affect endocrine therapy efficacy. ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT is an effective non-invasive method to analyze systemic ER expression. This study aimed to examine the predictive/prognostic value of ¹⁸F-FES PET/CT for patients treated with endocrine therapy plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

Methods: Patients were identified from a prospective cohort for post-marketing surveillance of ¹⁸F-FES enrolled between April 2021 and April 2023 at Asan Medical Center. In this retrospective analysis, patients with ER-positive, HER2-negative recurrent/metastatic breast cancer who underwent CDK4/6 inhibitor-based endocrine therapy and pre-treatment ¹⁸F-FES PET/CT were included.

Results: A total of 127 women were included. The endocrine therapy used was aromatase inhibitors in 96 patients (76%) and fulvestrant in 31 patients (24%). There were 25 (20%) and 102 (80%) patients in the "with FES-negative" (3 completely negative, 22 mixed) and "FES-positive" groups, respectively. ¹⁸F-FES status correlated with progression-free survival (PFS) following endocrine therapy with CDK4/6 inhibitors and overall survival (OS) ("with FES-negative" group: hazard ratio for PFS, 3.9, p < 0.001; for OS, 3.7, p = 0.008). Reduced benefit from endocrine treatment in the "with FES-negative" group was consistent across subgroups including menopausal status, endocrine sensitivity, and treatment regimen.

Conclusion: ER expression determined by ¹⁸F-FES PET/CT predicted the efficacy of CDK4/6 inhibitor-based endocrine therapy and was prognostic for survival in recurrent/metastatic ER-positive, HER2-negative breast cancer.