| Abstract | CILJ ISTRAŽIVANJA: Istražiti kliničke osobitosti bolesnica, karakteristike bolesti, način
liječenja i ishode liječenja kod bolesnica s nasljednim karcinomom dojke i jajnika koje su
dijagnosticirane, liječene i praćene u Klinici za onkologiju i radioterapiju Kliničkog bolničkog
centra Split u razdoblju od 01. listopada 1999. do 01. travnja 2021. godine.
ISPITANICE I METODE: Retrospektivno su prikupljeni podatci iz povijesti bolesti 15
bolesnica oboljelih od nasljednog karcinoma dojke i jajnika u razdoblju od 01. listopada 1999.
do 01. travnja 2021. godine. Prikupljeni podatci uključivali su dob bolesnice u trenutku
dijagnoze bolesti, obiteljsku anamnezu za zloćudne bolesti, primarno sijelo bolesti, histološki
podtip, stupanj diferenciranosti tumora, imunofenotip karcinoma dojke, stadij bolesti, BRCA
status, vrste BRCA mutacija, osobitosti kirurškog i onkološkog liječenja, specifičnosti
metakrono nastalih bilateralnih karcinoma dojke, specifičnosti sinkrono nastalih karcinoma
dojke i jajnika te ishod liječenja kroz ukupno preživljenje.
REZULTATI: Medijan dobi bolesnica u trenutku dijagnoze raka dojke iznosio je 53 godine, a
za karcinom jajnika 56 godina. Pozitivna obiteljska anamneza potvrđena je u 13 (87%)
bolesnica. Karcinom jajnika se najčešće (93%) dijagnosticirao u FIGO stadiju III i IV. Primarno
sijelo bolesti u bolesnica s rakom jajnika, jajovoda i potrbušnice bio je jajnik (67%), seroznog
papilarnog histološkog podtipa gradusa 3 (100%). Karcinom dojke se najčešće dijagnosticirao
u stadiju IA i IIA (67%), bio je najčešće duktanog histološkog podtipa (80%) gradusa 3 (56%),
jednake zastupljenosti trostruko negativnog i luminalnog imunofenotipa (46,7% za oba
imunofenotipa). Sve bolesnice su imale potvrđenu BRCA mutaciju, s prevagom mutacija
BRCA1 gena (80%). Najčešća BRCA mutacija u našoj studijskoj populaciji je BRCA1m
c.5266dupC i detektirana je kod 6 bolesnica. Bolesnice (87%) s karcinomom jajnika liječene su
inicijalno primarnom citoredukcijom (87%) koju je slijedila kemoterapija temeljenu na platini.
Olaparib je ordiniran u 7 (46,7%) bolesnica. Sve bolesnice s karcinomom dojke liječene su
inicijalno kirurškim putem, a ovisno o stadiju i imunofenotipu definirano je adjuvantno liječenje
kemoterapijom (93%), radioterapijom (60%) i hormonskom terapijom (60%). Medijan
ukupnog preživljenja bolesnica s nasljednim karcinomom dojke i jajnika na našem uzorku nije
dosegnut. Četiri bolesnice s metakronim bilateranim rakom dojke su imale pozitivnu obiteljsku
anamnezu na rak dojke. U svih bolesnica su najprije dijagnosticirani karcinomi dojke, a potom
karcinom jajnika. Najčešća BRCA mutacija u bolesnica s bilateralnim karcinomom dojke bila
je BRCA1m c.5266dupC. Dvije bolesnice su sinkrono razvile karcinom dojke i jajnika.
Bolesnica s BRCA1 mutacijom c.843_846delCTCA uz VUS BRCA2 gena razvila je trostruko
negativni rak dojke, a druga bolesnica s BRCA2 mutacijom luminalni B HER2 negativni rak
dojke.
ZAKLJUČAK: Kliničke osobitosti bolesnica s nasljednim karcinom dojke i jajnika,
patohistološke osobitosti tumora kao i ishodi liječenja u našoj studijskoj populaciji su
usporedivi s podatcima kliničkih studija objavljenih u dostupnoj svjetskoj medicinskoj
literaturi, respektirajući specifičnosti različitih naroda i rasa. |
| Abstract (english) | OBJECTIVE: To investigate the clinical characteristics of patients, disease characteristics,
treatment and treatment outcomes in patients with hereditary breast and ovarian cancer who
were diagnosed, treated and monitored at the Clinic of Oncology and Radiotherapy of the
University Hospital of Split in the period from October 1, 1999 to April 1 2021.
PATIENTS AND METHODS: The data were collected retrospectively from the medical
history of 15 patients with hereditary breast and ovarian cancer in the period from October 1,
1999 to April 1, 2021. Data collected included age of patient at diagnosis, family history of
malignancies, primary disease, histological subtype, degree of tumor differentiation, breast
cancer immunophenotype, stage of disease, BRCA status, types of BRCA mutations, features
of surgical and oncological treatment, specific of metachronous bilateral breast cancers, the
specifics of synchronous breast and ovarian cancers and the outcome of treatment through
overall survival.
RESULTS: The median age of patients at the time of diagnosis of breast cancer was 53 years,
and for ovarian cancer 56 years. A positive family history was confirmed in 13 (87%) patients.
Ovarian cancer was most often (93%) diagnosed in FIGO stage III and IV. The primary site of
disease in patients with ovarian, fallopian, and peritoneal cancers was the ovary (67%), serous
papillary histological subtype grade 3 (100%). Breast cancer was most commonly diagnosed in
stage IA and IIA (67%), most often duct histological subtype (80%) grade 3 (56%), equal
representation of triple-negative and luminal immunophenotype (46.7% for both
immunophenotypes). All patients had a confirmed BRCA mutation, with a predominance of
BRCA1 gene mutations (80%). The most common BRCA mutation in our study population is
BRCA1m c.5266dupC detected in 6 patients. Patients (87%) with ovarian cancer were initially
treated with primary cytoreduction (87%) followed by platinum-based chemotherapy. Olaparib
was administered to 7 (46.7%) patients. All patients with breast cancer were initially treated
surgically, and depending on the stage and immunophenotype, adjuvant treatment with
chemotherapy (93%), radiotherapy (60%) and hormone therapy (60%) was defined. The
median overall survival of patients with hereditary breast and ovarian cancer in our sample was
not reached. Four patients with metachronic bilateral breast cancer had a positive family history
of breast cancer. All patients were diagnosed with breast cancer first and then ovarian cancer.
The most common BRCA mutation in patients with bilateral breast cancer was BRCA1m
c.5266dupC. Two patients synchronously developed breast and ovarian cancer. A patient with
the BRCA1 mutation c.843_846delCTCA in addition to the VUS BRCA2 gene developed triple-negative breast cancer, and another patient with the BRCA2 mutation developed luminal
B HER2-negative breast cancer.
CONCLUSION: The clinical features of patients with hereditary breast and ovarian cancer,
pathohistological features of tumors and treatment outcomes in our study population are
comparable with data from clinical studies published in the available world medical literature,
respecting the specifics of different nations and races. |
