PIK3CA MUTATIONS IN LUMINAL, HER2 NEGATIVE METASTATIC BREAST CANCER

Abstract

Objectives: In patients with luminal, HER2-negative, metastatic breast cancers resistant to endocrine therapy, treated at KBC Split in 2020 and 2021, the proportion and type of PIK3CA mutations in tumor tissue samples was determined, and the obtained data was compared with the results from the registration study SOLAR1, which evaluates efficacy and safety of alpelisib in combination with fulvestrant in patients with advanced breast cancer that progressed during or after aromatase inhibitor treatment.

Subjects and methods: Retrospective analysis collected data on 99 patients diagnosed with luminal, HER2-negative, metastatic breast cancer in the period from 2020 to 2021. For the purposes of creating the empirical part of this thesis, the medical documentation and electronic database of the Clinical Institute for Pathology, Forensic Medicine and Cytology of the University Hospital of Split were accessed. Age, gender, presence of PIK3CA mutation and distribution of specific mutations were included in the database. Tumor tissue samples were analyzed using the RT-PCR method.

Results: A significant difference in the representation of patients according to gender was found in the sample of 99 patients. The largest number of patients is in the age group of 60 to 70 years, while the average age is 67 years. In 99 tissue samples from patients with metastatic, hormone receptor-positive, HER2-negative breast cancer, who are resistant to endocrine therapy treated at the University Hospital of Split, PIK3CA mutation was found in 50 of them (51.51%). In 17 tissue samples positive for the PIK3CA mutation (N=50), the H1047X mutation on exon 20 and 14 mutations on exon 9 (E542,545X and 545K) were found. These mutations represent 62% of all PIK3CA mutations, which corresponds to the results of the SOLAR-1 study, in which mutations were also found most frequently in exons 9 and 20.

Conclusion: Based on the results of this study, comparable to the results of the registration study SOLAR-1, the RT-PCR methodology used for the detection of PIK3CA mutations is an efficient, specific and sensitive method for selecting patients for PI3K inhibitor treatment, which can be implemented in a larger number of laboratories with regular external and internal checks on the quality and accuracy of testing.