Postradiation angiosarcoma of the breast: a 25-year single-institution analysis of clinicopathological characteristics and immunohistochemical biomarker study

We examined the clinicopathologic features and immunohistochemical expression of commonly tested biomarkers relevant to targeted therapy in postradiation angiosarcoma (PRAS) of the breast, aiming to better understand tumor biology and provide baseline data on tumor biomarkers to inform future therapeutic strategies for PRAS. Clinicopathologic features, outcomes, and the immunohistochemical expression of tumor biomarkers, including human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), and DNA mismatch repair proteins (MMR), were analyzed in breast PRAS specimens diagnosed from 2000 to 2024. A total of 24 breast PRAS specimens from 18 patients were included in the study. All PRAS patients were female, with a median age of 72 years at the time of diagnosis. High-grade tumors were observed in 47%, 43%, and 65% of specimens according to Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC), Donnell-Rosen, and Kuba scoring methods, respectively. Surgical intervention, adjuvant chemotherapy, and radiotherapy were administered to 100%, 29%, and 23% of patients, respectively. Five patients (29%) died from the disease during a median follow-up period of 37 months. Exploratory analysis showed there was no significant association between histologic grade and overall survival, regardless of the grading system used. All PRASs were MMR-proficient with a low number of tumor-infiltrating lymphocytes (TILs) and exhibited an absence of HER2 protein expression. PD-L1 was positive in seven (32%) specimens and positively correlated with stromal TILs. Our findings suggest that breast PRAS are genomically stable and poorly immunogenic, and are likely ineligible for any HER2-targeted therapies based on current approval criteria. A subset of specimens demonstrated PD-L1 positivity, underscoring the need for further investigation of immunotherapy with anti-PD1/PD-L1 immune checkpoint inhibitors as a potential treatment option.