| Abstract | CILJ ISTRAŽIVANJA: Osnovni cilj ovog istraživanja bio je usporediti kliničko-patološke značajke tumora dojke s prekomjernom ekspresijom HER2 proteina s tumorima ostalih imunofenotipova, te utvrditi povezanost s dobi bolesnika, vrstom tumora, veličinom tumora, fokalnošću, histološkim tipom, gradusom, Ki-67 prolifereracijskim indeksom i kliničkim stadijem.
MATERIJALI I METODE: U studiju su uključeni bolesnici kojima je karcinom dojke dijagnosticiran u Republici Hrvatskoj u razdoblju od 01.01.2017. do 31.12.2017. Uvidom u medicinsku dokumentaciju KBC-a Split, Klinike za tumore Zagreb, KBC-a Zagreb, KBC-a Rijeka, KBC-a Osijek, KBC-a Sestre milosrdnice, KB Dubrava, OB Zadar, OB Šibenik, OB Pula, ŽB Čakovec, OB Slavonski Brod, Poliklinike Edumed, Poliklinike Eljuga, OB Našice i OB Knin dobiveni su podaci o dobi bolesnika, veličini tumora, histološkom tipu, gradusu, fokalnosti, bilateralnosti, statusu hormonskih receptora, HER2 statusu, proliferacijskom indeksu, imunofenotipu, kliničkom stadiju, te primijenjenom kirurškom i onkološkom liječenju. Za usporedbu kvantitativnih podataka između istraživanih skupina korišteni su T-test, Mann-Whitneyev U test, Kruskal-Wallis test ovisno o broju skupina i raspodjeli kvantitativne varijable. Za utvrđivanje povezanosti dvaju kvalitativnih varijabli korišten je hi-kvadrat test.
REZULTATI: U Republici Hrvatskoj u 2017. godine registrirano je 2613 bolesnika sa karcinomom dojke. Podatci o HER2 statusu bili su dostupni za 2597 (99,4%) bolesnika, od čega je HER2 pozitivan status zabilježen kod 500 (19,3%) bolesnika. a HER2 negativan status kod 2097 (80,7%) bolesnika. Medijan dobi u skupini bolesnica s luminalnim B/HER2 pozitivnim imunofenotipom za 6 je godina manji nego u skupini luminalnog A (P<0,023) i skupini luminalnog B imunofenotipa (P=0,001). Udio tumora sa pozitivnim HER2 statusom (tumori Luminalnog B/HER2 pozitivnog imunofenotipa i HER2 pozitivnog imunofenotipa) značajno je veći u skupini neoadjuvantno liječenih i inicijalno metastatskih u odnosu na kompletno operirane tumore (P<0,001). Medijan veličine tumora luminalnog B/HER2 pozitivnog imunofenotipa i HER2 pozitivnog imunofenotipa je za 0,45 cm (P<0,001), te 0,5 cm (P<0,001) veći odnosu na medijan veličine tumora luminalnog A imunofenotipa. Udio tumora sa pozitivnim HER2 statusom značajno veći u skupini multifokalnih tumora (Udio tumora sa pozitivnim HER2 statusom značajno manji u skupini tumora invazivnog lobularnog histološkog podtipa (P=0,031). Udio tumora histološkog gradusa 3 u skupini tumora sa pozitivnim HER2 statusom značajno veći u odnosu na tumore Luminalnog A imunofenotipa (P<0,001). Medijan proliferacijskog indeksa u skupini tumora Luminalnog B/HER2 pozitivnog imunofenotipa iznosio 30%, a u skupini tumora HER2 pozitivnog imunofenotipa 40%, što je značajno više u odnosu na medijan proliferacijskog indeksa u skupini tumora luminalnog A imunofenotipa (10%) (P<0,001). U obje skupine tumora sa pozitivnim HER2 statusom kod većeg je broja bolesnika bolest dijagnosticirana u uznapredovalom kliničkom stadiju (klinički stadij 4) u odnosu na tumore Luminalnog A imunofenotipa (P <0,001).
ZAKLJUČCI: Tumori s povećanom ekspresijom HER2 receptora čine oko 15-30% tumora dojke. To su tumori agresivnijih kliničko-patoloških karakteristika: većeg dijametra, višeg gradusa, višeg proliferacijskog indeksa, češće se javljaju u uznapredovalom kliničkom stadiju, uz veći incidenciju kod bolesnica mlađe životne dobi. Unatoč agresivnijem kliničko-patološkom ponašanju, napretkom suvremene medicine kao i razvojem ciljane terapije te imunoterapije, bolesnici s ovom vrstom tumora danas imaju na raspolaganju različite mogućnosti liječenja, uz više šanse za izliječenje. |
| Abstract (english) | OBJECTIVES: The main aim of this study was to compare the clinico-pathological characteristics of breast tumors with increased expression of HER2 protein with the other immunophenotypes, and to establish correlation with age, tumor type, tumor size, focality, histological type, tumor grade, Ki-67 index value and clinical stage.
PATIENTS AND METHODS: The study included patients diagnosed with breast cancer in Croatia in the period from 01.01.2017. till 31.12.2017. Clinical data was obtained from the medical documentation of CHC Split, Clinic for Tumors Zagreb, CHC Zagreb, CHC Rijeka, CHC Osijek, CHC Sestre milosrdnice, CH Dubrava, GH Zadar, GH Sibenik, GH Pula, CH Čakovec, GH Slavonski Brod, Polyclynic Edumed and Eljuga, GH Nasice and GH Knin regarding the patient age, tumor size, histological type, tumor grade, focality, bilaterality, hormone receptor status, HER2/neu status, proliferation index, immunophenotype, clinical stage and the surgical and oncological treatment. For comparison of quantitative data between the investigated groups, T-test, Mann-Whitney U test, Kruskal-Wallis test were used, depending on the number of groups and the distribution of quantitative variables. To establish the correlation between the two qualitative variables, the chi squared test was used.
RESULTS: In Croatia, 2613 patients with breast cancer were registered in 2017. For 2597 (99.4%) patients HER2 status was available, and 500 (19.3%) tumors were HER2 positive, while 2097 (80.7%) tumors were HER2 negative. The median age in the group with luminal B/HER2 positive immunofenotype was 6 years lower than in the luminal A (P<0.023) and the luminal B immunophenotype group (P=0.001). The proportion of tumors with positive HER2 status (Luminal B/HER2 positive immunophenotype and HER2 positive immunofenotype) was significantly higher in the group of neoadjuvantly treated and initially metastatic tumors compared to completly operable tumors (P<0,001). The median size of the tumors with luminal B/HER2 positive immunofenotype and HER2 positive immunophenotype was 0.45 cm larger (P<0.001) and 0.5 cm (P<0.001) larger than the median tumor size of the tumors with luminal A immunofenotype. The proportion of tumors with positive HER2 status was significantly lower in the invasive lobular histological subtype (P=0,031). The proportion of histologic grade 3 tumors was significantly higher in the group with positive HER2 status (P<0,001). The median proliferation index in the luminal B/HER2 positive immunofenotype tumor group was 30%, and 40% in the group with HER2 positive immunofenotype which is significantly higher than the median proliferation index in the luminal A immunofenotype tumor group (10%) (P<0,001). In both tumor groups with positive HER2 status, significantly higher number of patients was diagnosed in advanced clinical stage (Clinical Stage 4) compared to the tumors with luminal A immunofenotype (P<0,001).
CONCLUSION: Tumors with increased HER2 expression make 15-30% of all breast tumors. These tumors are characterised by aggressive clinico-pathological characteristics: higher diameter, higher grade, higher proliferation index, higher clinical stage, and higher incidence in younger patients. Despite the aggressive clinical-pathological behavior, due to the development of targeted therapy and immunotherapy, patients with this type of tumors nowdays have better prognosis related to advanced treatment options. |
