genetic alterations in breast cancer.

Aims: Activating somatic mutations or gene amplification of result in constitutive activation of its receptor tyrosine kinase, which is targetable in various solid tumours. Here, we sought to investigate the presence of genetic alterations in breast cancer (BC) and characterise the histological and genomic features of these tumours.

Methods: A retrospective analysis of 5,575 BCs previously subjected to targeted sequencing using the FDA-authorised Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay was performed to identify BCs with alterations. A histological assessment of -altered BCs was conducted, and their repertoire of genetic alterations was compared with that of BCs lacking genetic alterations, matched for age, histological type, oestrogen receptor/HER2 status and sample type.

Results: We identified 18 BCs (0.32%), including 9 primary and 9 metastatic BCs, with oncogenic/likely oncogenic genetic alterations affecting , including activating somatic mutations (n=4) or gene amplification (n=14). All -altered BCs were of high histological grade, although no distinctive histological features were observed. When compared with BCs lacking genetic alterations, no distinctive genetic features were identified. In two metastatic -altered BCs in which the matched primary BC had also been analysed by MSK-IMPACT, the mutations were found to be restricted to the metastatic samples, suggesting that they were late events in the evolution of these cancers.

Conclusions: genetic alterations are vanishingly rare in BC. -altered BCs are of high grade but lack distinctive histological features. Genetic alterations in might be late events in the evolution and/or progression of BC.