Background. Breast cancer maintains a leading position in the structure of morbidity and mortality from malignant neoplasms in women around the world. The heterogeneity of the course of this disease and the inevitable formation of resistance to antitumor drug therapy in its common forms remain key problems in clinical oncology. The discovery of mutations in the PIK3CA gene, encoding the catalytic subunit p110-α of phosphatidylinositol 3-kinase (PI3K), identified a target for therapeutic intervention and the creation of an effective drug alpelisib.
Objective. Analysis of the frequency and spectrum of PIK3CA mutations in Russian patients with EC+/HER2-breast cancer within one center.
Methods. The study included 42 patients with ER+/HER2- breast cancer. The study was carried out on a closed COBAS amplifier. After microdissection of the material, deparaffinization and DNA extraction, DNA concentration was analyzed using a Qubit fluorimeter, followed by COBAS sets of 1, 4, 7, 9 and 20 exons using a closed-type amplifier. The validity of all statements and samples was determined by the COBAS 4800 program. Information on the clinical and morphological characteristics of the tumor was extracted from the regional information system. Statistical analysis was performed using StatTech 4.1.1 software.
Results. Samples from 42 patients were tested. The average age of the patients at the time of diagnosis was 59.8 years. There was a predominance of patients with the luminal B HER2-negative subtype. Mutations in the PIK3CA gene were detected in 17 samples out of 42, which amounted to 40.5%. The 3 most common mutations accounted for 82% of cases: p.H1047X (6/17, 35%), pE542K (4/17, 23.5%) and p. E545X (4/17, 23.5%). A total of 6 mutations were detected in exon 20, 8 mutations in exon 9, and 3 mutations in exon 4 of the PIK3CA gene. In addition, 1 case of double mutation N345K-H1047R was identified. The mean age at diagnosis was 63.4 years in the group with a mutation in the PIK3CA gene and 57.4 years in the group without a mutation in the PIK3CA gene (p=0.14). The results of the analysis of the relationship between clinicopathological characteristics (stage, molecular subtype of the tumor, the presence of visceral metastases, localization and number of affected areas) did not differ statistically and clinically significantly between the groups of patients with and without a mutation in the PIK3CA gene.
Conclusion. The obtained data on the spectrum of somatic PIK3CA aberrations can be used for planning treatment with PI3K inhibitors in our population, for organizing molecular genetic testing of breast cancer patients in a regional dispensary and outside the region. It is planned to continue this study and evaluation the association of the PIK3CA gene mutation with the clinical and morphological characteristics of breast cancer.

Keywords: PIK3CA mutation spectrum, hormone-dependent HER2-negative breast cancer, PI3KA, PIK3CA, alpelisib