The impact of MYC gene amplification on the clinicopathological features and prognosis of radiation‐associated angiosarcomas of the breast.

Aims: Radiation‐associated angiosarcomas (RT‐ASs) of the breast are rare tumours with a poor prognosis. MYC gene amplification is considered to be the hallmark of RT‐AS, and is sometimes used as a diagnostic tool to distinguish it from other radiation‐associated vascular lesions. However, a small subset of RT‐ASs lacks MYC amplification, and this may be associated with better outcome. Loss of trimethylation at lysine 27 of histone 3 (H3K27me3) expression by immunohistochemistry (IHC) has been recently postulated as an additional diagnostic marker for RT‐AS. The aims of this study were to evaluate the impact of MYC amplification as detected by fluorescence in‐situ hybridisation and/or next‐generation sequencing on clinicopathological features and outcome in a large cohort of RT‐ASs, compare outcome with those of radiation‐associated sarcomas (RT‐Ss) of the breast other than angiosarcoma, and evaluate expression of H3K27me3 IHC in these groups. Methods and results: Eighty‐one RT‐ASs were identified, including 73 that were MYC‐amplified and 8 (10%) that were MYC‐non‐amplified. MYC‐amplified RT‐ASs were diagnosed in older patients (median age, 69 years versus 61 years). The 5‐year disease‐specific survival and 5‐year overall survival rates were 56% and 47%, respectively. Older age, larger tumour size, positive margin and MYC amplification were associated with worse prognosis. None of the RT‐ASs showed complete loss of H3K27me3 IHC expression. All 18 RT‐Ss were MYC‐non‐amplified, and complete loss of H3K27me3 expression was seen in 2 cases. We found no difference in prognosis between RT‐AS and RT‐S. Conclusions: RT‐AS of the breast is associated with a poor prognosis. Older age at diagnosis, larger tumour size, positive margin at excision and MYC amplification are associated with worse prognosis. [ABSTRACT FROM AUTHOR]