PIK3CA mutations in luminal, HER2 negative metastatic breast cancer

Ciljevi: U bolesnica s luminalnim, HER2 negativnim, metastatskim karcinomima dojke rezistentnim na endokrinu terapiju, liječenim u KBC Split u 2020. i 2021. godini u uzorcima tkiva tumora odrediti udio i tip PIK3CA mutacija, te dobivene podatke usporediti s rezultatima iz registracijske SOLAR-1 studije. Ispitanici i postupci: Prikupljeni su podaci o 99 bolesnika s dijagnosticiranim luminalnim, HER2 negativnim, metastatskim karcinomima dojke u vremenskom periodu od 2020. i 2021. godine. To je retrospektivna analiza. Za potrebe izrade empirijskog dijela ovog diplomskog rada pristupljeno je medicinskoj dokumentaciji i elektroničkoj bazi podataka Kliničkog zavoda za patologiju,sudsku medicinu i citologiju Kliničkog bolničkog centra Split. U bazu podataka uvršteni su dob, spol, prisutnost PIK3CA mutacije i distribucija specifičnih mutacija. Uzorci tumorskog tkiva analizirani su primjenom RT-PCR metode. Rezultati: Utvrđena je značajna razlika u zastupljenosti pacijenata prema spolu u uzorku od 99 pacijenata. Najveći broj pacijenata nalazi se u dobnoj skupini od 60 do 70 godina, dok srednja životna dob iznosi 67 godina. U 99 uzoraka tkiva pacijenata s metastatskim, hormon receptor pozitivnim, HER2 negativnim karcinomom dojke , koji su rezistentni na endokrinu terapiju liječenih u KBC-u Split, u njih 50 je nađena PIK3CA mutacija (51,51%). U 17 uzoraka tkiva pozitivnih na PIK3CA mutaciju (N=50) utvrđena mutacija H1047X na egzonu 20, te 14 mutacija na egzonu 9 (E542,545X i545K). Ove mutacije predstavljaju 62% svih PIK3CA mutacija, što odgovara rezultatima SOLAR-1 studije, u kojoj su mutacije također nađene najčešće na egzonima 9 i 20. Zaključak: Na temelju rezultata ove studije, usporedivih s rezultatima registracijske studije SOLAR-1, RT-PCR metodologija korištena za detekciju PIK3CA mutacija je efikasna, specifična i senzitivna metoda za odabir bolesnica za liječenje PI3K inhibitorom, koja se može implementirati u većem broju laboratorija uz redovite vanjske i unutarnje provjere kvalitete i točnosti testiranja.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 SOLAR-1 study. 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