This study aimed to investigate the clinicopathological characteristics and prognostic factors of primary osteosarcoma of the breast (POB), providing evidence for optimizing diagnostic and therapeutic strategies for this rare malignancy.

Clinical data were retrospectively collected from patients with pathologically confirmed breast tumors containing osteosarcomatous components. All patients were treated at the Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, between February 2006 and July 2025. Collected data included clinical presentation, imaging findings, pathological features, treatment modalities, and follow-up outcomes. A single-cohort analysis was performed in POB patients, and intergroup comparisons were conducted between POB patients and non-POB patients which were defined as those with other breast malignancies containing osteosarcomatous components, including malignant phyllodes tumor with osteosarcoma (MPTB-OS) and metaplastic breast carcinoma with osteosarcoma (MBC-OS). Disease-free survival (DFS) was assessed using the Kaplan-Meier method to compare prognostic differences between the two groups and evaluate the impact of surgical modalities and adjuvant therapies on DFS in POB patients.

A total of 16 female patients were included, aged 37 years-76 years (median, 53 years). Among them, 8 (50.0%) were POB patients, 5 (31.3%) were MPTB-OS patients, and 3 (18.8%) were MBC-OS patients. All patients underwent surgery. Six patients received sentinel lymph node biopsy or axillary lymph node dissection, and none showed nodal metastasis. No deaths occurred during follow-up, and the 1-year and 2-year recurrence or metastasis rates were 37.5% (95% CI: 8.5%-75.5%) and 62.5% (95% CI: 24.5%-91.5%), respectively, whereas those for the non-POB patients were 0 (95% CI: 0-36.9%) and 12.5% (95% CI: 0.3%-52.7%). POB patients exhibited significantly poorer DFS than non-POB patients (P=0.009). Neither surgical approach nor adjuvant therapy showed a significant association with DFS in POB patients.

POB patients exhibited a significantly higher risk of recurrence and distant metastasis and poorer DFS than non-POB patients. Survival analysis didn't indicate that mastectomy surgery, axillary lymph node surgery, or postoperative adjuvant therapy was associated with a significant difference in DFS among POB patients.