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.