Title PIK3CA mutacije u luminalnim, HER2 negativnim metastatskim karcinomima dojke
Title (english) PIK3CA mutations in luminal, HER2 negative metastatic breast cancer
Author Domagoj Krželj
Mentor Snježana Tomić (mentor)
Committee member Branka Petrić Miše (predsjednik povjerenstva)
Committee member Ivana Mrklić (član povjerenstva)
Committee member Ivana Pavlinac Dodig (član povjerenstva)
Granter University of Split School of Medicine Split
Defense date and country 2022, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Pathology
Abstract 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.
Abstract (english) 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.
Keywords
PIK3CA mutacije
distribucija PIK3CA mutacija
obilježja pacijenata prema dobu i spolu
lijek alpelisib
SOLAR-1 studija
hormon pozitivni i HER2 negativni rak dojke rezistentan na endokrinu terapiju
Keywords (english)
PIK3CA mutations
distribution of PIK3CA mutations
representation of patients acording to gender and age
cure alpelisib
SOLAR-1 study
hormone receptor positive and HER2 negative breast cancer resistant to endocrine therapy
Language croatian
URN:NBN urn:nbn:hr:171:224654
Study programme Title: Medicine Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
File origin Born digital
Access conditions Open access Embargo expiration date: 2023-07-29
Terms of use
Created on 2022-07-22 08:51:34