Association Between Immunohistochemical Profile and Radiographic Presentation of Breast Cancer Skeletal Metastases

Background/Objectives: Understanding the biological factors that drive the behavior and clinical presentation of breast cancer (BC) skeletal metastases (SM) is critical for improving diagnostic accuracy and guiding treatment strategies. However, evidence regarding the immunohistochemical (IHC) profiles of SM and their association with radiographic characteristics and clinical features remains limited. This study aimed to evaluate the relationship between estrogen receptor (ER), progesterone receptor (PR), HER2 receptor status, and Ki-67 proliferation index with the radiographic presentation of SM in patients with BC. Methods: A total of 185 SM samples from individual BC patients were analyzed. IHC expressions of ER, PR, HER2, and Ki-67 were determined for each sample. Clinical and radiological data were retrieved from medical records. IHC profiles were compared between metastases demonstrating purely lytic versus mixed radiographic patterns. Results: Of the 185 cases, 66 exhibited a lytic pattern, and 119 demonstrated a mixed pattern. Lytic metastases showed a significantly higher rate of HER2 positivity compared with mixed lesions. The Ki-67 index was also significantly higher in lytic metastases, with a cutoff value of 25 yielding a sensitivity of 92.98% and specificity of 89.84% (positive likelihood ratio 9.16; negative likelihood ratio 0.08). No significant differences were observed between groups in ER or PR expression. Conclusions: SM from BC with a lytic radiographic presentation are more likely to exhibit HER2 positivity and a Ki-67 index above 25. Assessing the IHC status of SM may help identify patients at elevated risk for skeletal complications, including pathological fracture, and may support more tailored surgical and systemic treatment planning.