Results of multicenter testing of PIK3CA somatic mutations in hormone-receptor positive HER2-negative advanced breast cancer

Aim: Activating somatic mutations in p110α catalytic subunit of PIK3-kinase (PIK3CA) are present in about 40% of breast cancers (BC), and are involved in oncogenesis and cancer growth. PIK3CA inhibitor therapy is approved for patients with advanced HR+/HER2- endocrine-resistant BC with somatic PIK3CA mutations. Such targeted therapy improved patient disease-free survival. Method: Analyses of PIK3CA gene mutations were performed in five University Hospital Centers in Croatia. Qualitative detection of PIK3CA gene mutations was performed on DNA extracted from 507 breast cancer samples, by the real-time PCR method using Cobas® PIK3CA mutation test. Results: PIK3CA gene mutations were detected in 209 (42.2%) out of 495 successfully analyzed cases. In 12 cases (2.4%), the tumor tissue was not of sufficient quality for analysis. Most mutations were detected in the helical (41.2%) and kinase domains (46.9%) of the PIK3CA protein. The most frequently detected mutations were H1047L/R/Y (46.4%), E545A/D/G/K (26.3%) and E542K (13.9%), followed by N345K (8.1%). PIK3CA mutations were detected in 44.8% of primary BC cases and in 39.6% of metastatic lesions (χ2=0.647; P=0.421). The age of the tissue did not significantly affect the percentage of detected mutations (χ2=0.543; P =0.461). Institutions differed in the number of analyzed cases, but not in the percentage of detected PIK3CA mutations (χ2=6.23; df=4; P=0.183) nor in the frequency of the most common mutations (χ2=2.65; df=4; P=0.618). Conclusion: The frequencies of PIK3CA mutations correspond to those reported in the literature. We have shown that the tissue of primary BC as well as metastatic lesions are suitable for analysis, and that the age of the tissue is not a significant obstacle in the analysis.