Targeted adjuvant therapy for breast cancer

Abstract

Karcinom dojke je jedna od najčešće dijagnosticiranih malignih bolesti u svjetskoj populaciji. Incidencija se razlikuje ovisno o dobi osobe, geografskom položaju države, izloženosti rizičnim čimbenicima i dostupnim mjerama prevencije (1,2). Gotovo 70% slučajeva karcinoma dojke dijagnosticirano je u dobi od 50 i više godina. Na svjetskoj razini, stope incidencije i mortaliteta značajno su više u tranzicijskim, slabije razvijenim zemljama u odnosu na ostatak svijeta (2,3). Prema podatcima Hrvatskog registra za rak, u 2020. godini zabilježeno je 2869 novih slučajeva karcinoma dojke, što ga čini najčešćim karcinomom kod žena u Hrvatskoj. (6) Među najznačajnijim čimbenicima rizika za razvoj karcinoma dojke nalaze se ženski spol, odstupanja od fizioloških razina spolnih hormona, dob starija od 50 godina, mutacije BRCA gena i pretilost (7-10). Osnovne metode postavljanja dijagnoze uključuju fizikalni pregled uz mamografiju ili ultrazvuk te patohistološku analizu uzorka dobivenog biopsijom (1, 17). Terapija karcinoma dojke ovisi o histološkom i molekularnom tipu karcinoma te TNM stadiju. Prvi korak u terapiji invazivnog karcinoma uključuje poštednu operaciju (lokalna ekscizija, lumpektomija) uz onkoplastične tehnike rekonstrukcije. Nakon provedene histološke i molekularne procjene može se primijeniti adjuvantna terapija (17,24). Jedna od opcija je ciljana adjuvantna terapija, usmjerena na karakteristične proteine stanice tumora i signalne puteve čime postiže inhibiciju proliferacije i rasta malignih stanica (25,26). Rezultati ispitivanja ciljane terapije pokazali su učinak na produljenje preživljenja i smanjenje učestalosti recidiva kod bolesnica s invazivnim karcinomom dojke. S tim ciljem, FDA je odobrila nekoliko skupina lijekova uključujući HER2 ciljanu terapiju, PI3K, CDK4/6 i PARP inhibitore (31,32). Ovaj rad prezentira rezultate dosadašnjih istraživanja učinkovitosti primjene navedenih skupina lijekova u adjuvantnom liječenju karcinoma dojke.Breast cancer is one of the most frequently diagnosed malignant diseases in the world. The incidence varies depending on a person's age, geographic location of the country, exposure to risk factors, and available methods for prevention (1,2). More than 70% of breast cancer cases are diagnosed at the age of 50 and older. At the global level, incidence and mortality rates are significantly higher in transitional, less developed countries compared to the rest of the world 2,3). According to data from the Croatian Cancer Registry, 2,869 new cases of breast cancer were recorded in 2020, making it the most common cancer among women in Croatia (6). The most significant risk factors for the development of breast cancer include female sex, deviations from the physiological levels of sex hormones, age older than 50 years, BRCA gene mutations and obesity (7-10). The basic methods of diagnosis include physical examination with mammography or ultrasound and pathohistological analysis of the biopsy sample (1, 17). Breast cancer therapy depends on the histological and molecular type of cancer and the TNM stage. The first step in the treatement of invasive cancer includes a sparing operation (local excision, lumpectomy) with oncoplastic reconstruction techniques. After a histological and molecular assessment, adjuvant therapy can be applied (23,24). One of the options is targeted adjuvant therapy, aimed at the characteristic proteins of tumor cells and signaling pathways, which achieves the inhibition of the proliferation and growth of malignant cells (25,26). The results of research regarding targeted adjuvant therapy showed an effect on prolonging survival and reducing the frequency of recurrence in patients with invasive breast cancer. Because of that discovery, the FDA has approved several classes of drugs including HER2 targeted therapy, PI3K, CDK4/6 and PARP inhibitors (31,32). This paper presents the results of research on the efficiency of application of the above mentioned groups of drugs in the adjuvant treatment of breast cancer