BACKGROUND

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).

OBJECTIVE

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.

MATERIAL AND METHODS

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.

RESULTS

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.

CONCLUSION

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.