[Characteristics of PIK3CA gene mutations in Her2-low breast cancer]

Mutations in the PIK3CA gene, encoding the catalytic subunit of the PI3K class IA p110α, is a common mechanism of activating of PI3K/AKT/mTOR pathway in breast cancer (BC). The detection of these mutations in patients with hormone-positive Her2-negative BC is of important clinical value, since they are the predictor of the sensitivity of the tumor to the PI3K inhibitor - alpelisib. According to the status of the Her2/neu expression, all patients with hormone-positive Her2-negative BC can be divided into two groups - with low expression of Her2/neu (IHC 1+; 2+, ISH-) and with a complete lack of expression of this protein (IHC 0).

Establish whether there are differences of the PIK3CA gene mutations charasteristics in BC with luminal immunophenotype and low expression of Her2/neu in comparison with tumors in which Her2/neu expression is absent.

The presence of PIK3CA mutations was determined using real-time PCR on 96 patient tissues of hormone-positive Her2-negative BC. Commercially available cobas PIK3CA Mutation Kit (Roche) and cobas z480 analyzer were used.

PIK3CA gene mutations were detected in 40 of 96 cases studied (41.6%). Most of them were localized in the exons 9 and 20, encoding helicase (p.E542K, p.E545X) or kinase (p.H1047X) domains of PI3K, respectively. The frequency of mutations in the exon 9 (p.E542K+p.E545X) was 2.6 times higher in Her2-low BC compared to tumors in which the Her2/neu expression was absent (p<0.05). There were no statistically significant differences in mutation frequency in the exon 20.

Statistically significant increase in the frequency of exon 9 mutations of the PIK3CA gene is specific for the group of patients with Her2-low BC. Our results supported the concept of Her2-low BCs as the unique entity and pointed out the need of their further study.