CDK4/6 Inhibition and Stereotactic Radiotherapy in Oligometastatic HR+/HER2− Breast Cancer: Evidence of Immunogenic Modulation and Pseudoprogression

Background: A combination of cyclin-dependent kinase 4/6 inhibitors (CDKi) and radiotherapy (RT) may enhance antitumoral immunity, yet clinical evidence of this interaction in HR+/HER2− metastatic breast cancer (MBC) remains limited. This study evaluates the impact of combined CDKi and stereotactic body radiotherapy (SBRT) on immune biomarkers and treatment response. Methods: We report a case of a 51-year-old woman with oligometastatic HR+/HER2− MBC involving the sacrum. Clinical management included letrozole plus palbociclib and SBRT (30 Gy in 3 fractions). Serial Neutrophil-to-lymphocyte ratio (NLR) measurements, MRI, and PET-CT scans were used to monitor systemic immune modulation and treatment efficacy over a five-year period. Results: Baseline NLR was 1.068. Following four weeks of CDKi, NLR decreased by 44.7% (0.591). Post-SBRT, a further 17.8% reduction was observed (nadir 0.486). Five months post-RT, MRI showed a volumetric increase in sacral lesions despite clinical improvement. Subsequent PET-CT demonstrated a complete metabolic response, confirming the MRI findings as pseudoprogression. As of January 2026, the patient remains in sustained complete metabolic remission. Conclusion: The integration of CDKi and SBRT might induce an immune-mediated antitumoral response, evidenced by dynamic NLR reductions and radiologic pseudoprogression. Multimodal imaging is essential to differentiate immune-mediated swelling from true progression in this setting.