New primary non-breast malignancies after breast cancer: ten years single institution follow-up

Background and Purpose: Breast cancer is the most common cancer in Croatian women. Due to improved diagnostic and treatment options women with breast cancer now live longer, which increases their risk of developing new primary malignancies. The aim of this study was to establish incidence of new primary non-breast malignancies after breast cancer diagnosis. Material and Methods: In the study cohort that included 215 consecutive patients treated for early breast cancer at University Hospital Center Zagreb, Croatia, 12 patients (5.58%) have developed new primary non-breast malignancy within nearly ten year follow-up. Results: Although the majority of studies found gynecological cancers to be the most common cancer site of new primary non-breast malignancies after breast cancer diagnosis, in our study most patients developed colorectal cancer. Conclusion: This is particularly interesting if you take into account that after breast cancer colorectal cancer is the second most common cancer in Croatian women. In order to stratify the risk for the development of new primary tumors it is necessary to further investigate the interaction of various factors that are thought to influence the evolvement of tumors

Prognostička vrijednost topoizomeraze 2-alfa i B-Myb u ranom raku dojke liječenom adjuvantnom kemoterapijom

Breast cancer is the most common malignancy in females. Despite its well-established prognostic factors, our prognostic ability at an individual patient level remains limited. In this study, the immunohistochemical expression of B-Myb and DNA topoisomerase 2-alpha (Topo2a) was analyzed in primary tumors to identify patients with a higher risk of disease recurrence after adjuvant chemotherapy for early invasive breast cancer. We analyzed a cohort of 215 early invasive breast cancer patients having undergone surgery from 2002 to 2003 at the Zagreb University Hospital Centre, including 153 patients treated with adjuvant chemotherapy. All of them were followed-up prospectively for at least ten years according to routine institutional practice. Statistically significant correlations were found between B-Myb and Topo2a expression levels and particular well-established prognostic factors. B-Myb expression was lower in estrogen receptor (ER)-positive tumors (p=0.0773), whereas larger tumors and those with positive lymphovascular invasion displayed a statistically significantly higher B-Myb expression (p=0.0409 and p=0.0196). Higher tumor grade indicated higher Topo2a values (p=0.0102 and p=0.0069). The subgroup with the expression of both proteins above the median value had an almost statistically significantly (p=0.0613) inferior prognosis compared to the rest of the cohort. Study results showed the B-Myb and Topo2a expression to have a prognostic value in breast cancer patients after adjuvant chemotherapy, which should be additionally explored in future studies in a larger patient cohort.Rak dojke je najčešći zloćudni tumor u žena. Unatoč dobro definiranim “tradicionalnim” prognostičkim čimbenicima naša mogućnost prognoze za svaku pojedinu bolesnicu je ograničena. U ovom istraživanju smo analizirali imunohistokemijsku izraženost B-Myb-a i DNA topoizomeraze 2-alfa (Topo2a) u primarnim tumorima kako bi se identificirale bolesnice s većim rizikom povrata bolesti nakon adjuvantne kemoterapije za rani invazivni rak dojke. Analizirana je kohorta od 215 bolesnica s ranim invazivnim karcinomima dojke koje su operirane u Kliničkom bolničkom centru Zagreb od 2002. do 2003. godine, uključujući 153 bolesnice koje su liječene adjuvantnom kemoterapijom. Sve su praćene prospektivno najmanje deset godina prema rutinskoj kliničkoj praksi. Dokazali smo statistički značajne korelacije između razine izraženosti B-Myb i Topo2a te nekih „tradicionalnih” prognostičkih čimbenika. Izraženost B-Myb je bila niža u ER pozitivnim tumorima (p=0,0773), ali su veći tumori, kao i oni s pozitivnom limfovaskularnom invazijom imali statistički značajno veću izraženost proteina B-Myb (p=0,0409 i p =0,0196). Također, pokazali smo da veći gradus tumora ukazuje na višu vrijednost Topo2a (p=0,0102 i p=0,0069). Pokazali smo da podskupina bolesnica s izraženošću oba proteina iznad srednje vrijednosti ima lošiji ishod bolesti u odnosu na ostatak skupine, ali rezultat je blizu granice statističke značajnosti (p=0,0613). Naše istraživanje je pokazalo prognostičku vrijednost kombinacije prekomjerne imunohistokemijske izraženosti B-Myb i Topo2a u bolesnica s rakom dojke nakon adjuvantne kemoterapije, što zaslužuje daljnja istraživanja na većim skupinama bolesnica

Chemotherapy – induced cognitive dysfunction – unrecognized side effect of cancer treatment

Oštećenja kognitivnih funkcija vrlo su česta nuspojava citotoksične terapije tijekom liječenja zloćudnih bolesti. Često ostaju neprepoznata zbog multifaktorijalne kompleksne etiologije i poteškoća pri mjerenju i objektivizaciji. U radu prikazujemo dijagnostičke mogućnosti procjene pojedinih kognitivnih disfunkcija, vrste kognitivnih poremećaja u tijeku liječenja zloćudnih bolesti i mogućnosti utjecaja na poboljšanje ovog važnog dijela kvalitete života oboljelih.Cognitive dysfunctions are very common side effects of chemotherapy. Still, remain unrecognized because of multifactorial and complex etiology and difficulties in measurement and objectivisation. In this review we present diagnostic possibilities of cognitive testing, sorts of cognitive deficits in cancer patients and possibilities of their treatment and prevention

Breast cancer : Clinical guidelines proposal

Prijedog kliničke smjernice “Rak dojke” izraðen je u okviru projekta reforme zdravstva na traženje Ministarstva zdravstva Republike Hrvatske, a izradila ga je Stručna grupa HLZ-a Hrvatskoga senološkog društva u sastavu: prof. dr. sc. Ivan Drinković, Poliklinika za radiologiju i ultrazvučnu dijagnostiku, Zagreb, Paula Podolski, dr. med., KBC Zagreb, Mladen Stanec, dr. med., Klinika za tumore, Zagreb, a na temelju smjernica: Scottish Intercollegiate Guidelines Network “Breast cancer”, New Zeland Guidelines Group “Guidelines for the Surgical Management of Breast Cancer”, te Canadian Medical Association “Questions and answers on breast cancer-A guide for women and their physicians”.Proposal for guidelines for the women breast cancer was made as a part of health reform project on demand of Ministery of Health, Republic of Croatia.It was made by Croatian Senology Society Working Group (Ivan Drinković,MD, PhD). Guidelines are based on: Scottish Intercollegiate Guidelines Network “Breast cancer”, New Zeland Guidelines Group “Guidelines for the Surgical Management of Breast Cancer” and Canadian Medical Association “Questions and answers on breast cancer · A guide for women and their physicians”. ”Guideline for clinical practice is systematicaly made documentation wich purpouse is to help physicians and patients to make decisions about clinical aproach to particulary clinical questions” (CEBM-Oxford

Patohophysiological and molecular bases of cognitive dysfunction in cancer patients

U suvremenoj znanstvenoj i stručnoj literaturi sve je više navoda o kognitivnim poremećajima u oboljelih od zloćudnih bolesti koji mogu biti uzrokovani samim zloćudnim procesom (smještaj unutar središnjeg živčanog sustava ili oštećenje tkiva u sklopu paraneoplastičkog sindroma), njegovim liječenjem (radioterapijom, kemoterapijom ili kirurškim tehnikama), genetskim čimbenicima, infekcijom, anemijom, promjenama u imunološkom sustavu, metaboličkim poremećajem i/ili nutritivnim deficitima. Mogu se pojaviti u ranoj fazi zloćudne bolesti, neposredno prije njezinog otkrivanja ili započinjanja liječenja, u tijeku liječenja, a mogu trajati dugo nakon uspješnog izlječenja. Poremećaji pamćenja, učenja, koncentracije, računanja ili razmišljanja bilježe se u rasponu od blagih do vrlo teških poremećaja, koji sliče presenilnoj demenciji. Kognitivni poremećaji za oboljele od zloćudne bolesti predstavljaju značajne smetnje zbog svog utjecaja na kvalitetu života, radnu sposobnost i društvene aktivnosti, stoga se danas u svjetu podupiru istraživanja patofizioloških mehanizama nastanka kognitivnih poremećaja u takvih pacijenata. Cilj je otkriti pacijente sa zloćudnom bolešću koji imaju povećanu sklonost razvoja kognitivnih poremećaja u času postavljanja dijagnoze ili na samom početku liječenja na osnovi svoje genske predispozicije, kako bi se terapija zloćudne bolesti mogla tome prilagoditi i po mogućnosti spriječiti posljedice kognitivnih oštećenja. U ovom radu prikazujemo pregled literature i dosadašnje spoznaje o patofiziološkim i imunopatofiziološkim mehanizmima povezanosti zloćudne bolesti i kognitivnih funkcija.Recent studies showed clear evidence of neurocognitive deficits in patients with malignant disease. Cognitive disorders in these patients may be due to the malignant tumor (localization in the CNS or tissue damage as a part of the paraneoplastic syndrome), its treatment, infection, anemia, immune, genetic and metabolic disorders, nutritional deficiency, or a combination of these and many other factors. The first studies on this topic have focused on cognitive dysfunction as a side effect of chemotherapy, but recent evidence shows that they can occur at any stage of the malignancy, even before diagnosis, during therapy and long time after succsessful cure. Learning, memorizing, concentration, thinking and other cognitive and psychomotor disturbances could vary from very mild to serious deficits like dementia. Cognitive dysfunction in cancer patients is an important issue, because of its impact on the everyday quality of life, especially in the working, cognitive and social activities. Although many previous studies on the subject found some role of various cytokines, genes and other factors, scientists agree that we are still far from complete explanation of complex etiology of cognitive impairment in patients with malignant diseases. The aim of those studies was to discover and prevent cognitive deterioration in vulnerable cancer patients.We present here the literature review and the findings on patophysiological and immunopatophysiological mechanisms of cognitive disfunctions in cancer patients

Patohophysiological and molecular bases of cognitive dysfunction in cancer patients

U suvremenoj znanstvenoj i stručnoj literaturi sve je više navoda o kognitivnim poremećajima u oboljelih od zloćudnih bolesti koji mogu biti uzrokovani samim zloćudnim procesom (smještaj unutar središnjeg živčanog sustava ili oštećenje tkiva u sklopu paraneoplastičkog sindroma), njegovim liječenjem (radioterapijom, kemoterapijom ili kirurškim tehnikama), genetskim čimbenicima, infekcijom, anemijom, promjenama u imunološkom sustavu, metaboličkim poremećajem i/ili nutritivnim deficitima. Mogu se pojaviti u ranoj fazi zloćudne bolesti, neposredno prije njezinog otkrivanja ili započinjanja liječenja, u tijeku liječenja, a mogu trajati dugo nakon uspješnog izlječenja. Poremećaji pamćenja, učenja, koncentracije, računanja ili razmišljanja bilježe se u rasponu od blagih do vrlo teških poremećaja, koji sliče presenilnoj demenciji. Kognitivni poremećaji za oboljele od zloćudne bolesti predstavljaju značajne smetnje zbog svog utjecaja na kvalitetu života, radnu sposobnost i društvene aktivnosti, stoga se danas u svjetu podupiru istraživanja patofizioloških mehanizama nastanka kognitivnih poremećaja u takvih pacijenata. Cilj je otkriti pacijente sa zloćudnom bolešću koji imaju povećanu sklonost razvoja kognitivnih poremećaja u času postavljanja dijagnoze ili na samom početku liječenja na osnovi svoje genske predispozicije, kako bi se terapija zloćudne bolesti mogla tome prilagoditi i po mogućnosti spriječiti posljedice kognitivnih oštećenja. U ovom radu prikazujemo pregled literature i dosadašnje spoznaje o patofiziološkim i imunopatofiziološkim mehanizmima povezanosti zloćudne bolesti i kognitivnih funkcija.Recent studies showed clear evidence of neurocognitive deficits in patients with malignant disease. Cognitive disorders in these patients may be due to the malignant tumor (localization in the CNS or tissue damage as a part of the paraneoplastic syndrome), its treatment, infection, anemia, immune, genetic and metabolic disorders, nutritional deficiency, or a combination of these and many other factors. The first studies on this topic have focused on cognitive dysfunction as a side effect of chemotherapy, but recent evidence shows that they can occur at any stage of the malignancy, even before diagnosis, during therapy and long time after succsessful cure. Learning, memorizing, concentration, thinking and other cognitive and psychomotor disturbances could vary from very mild to serious deficits like dementia. Cognitive dysfunction in cancer patients is an important issue, because of its impact on the everyday quality of life, especially in the working, cognitive and social activities. Although many previous studies on the subject found some role of various cytokines, genes and other factors, scientists agree that we are still far from complete explanation of complex etiology of cognitive impairment in patients with malignant diseases. The aim of those studies was to discover and prevent cognitive deterioration in vulnerable cancer patients.We present here the literature review and the findings on patophysiological and immunopatophysiological mechanisms of cognitive disfunctions in cancer patients

Lokalno liječenje moždanih metastaza raka dojke

Breast cancer, along with lung cancer and melanoma, is one of the most common origins of central nervous system metastases. Due to improvement of systemic therapy options for primary disease and consequential prolonged survival, treatment of brain metastasis (BM) is presenting an evolving challenge. While new systemic therapy approaches for breast cancer brain metastasis are focusing on overcoming the blood brain and blood tumor barrier, as well as targeted therapies, local therapy remains the primary line of treatment. The decision of which local therapies to use, depends upon the number and volume of BM, their localization, patient’s clinical status, previously used treatments, status of extracranial disease and patient’s prognosis. In cases when an active approach, including surgery and/or radiotherapy, does not bring benefit to the patient’s quality of life or overall survival, best supportive care is recommended.Rak dojke, uz tumore pluća te melanom, najčešći je tumor koji metastazira u središnji živčani sustav. Uslijed razvitka sistemske terapije primarne bolesti, i posljedičnog produljenog preživljenja bolesnika, liječenje moždanih metastaza predstavlja sve veći izazov. Dok se novi pristupi sistemskoj terapiji moždanih presadnica tumora dojke fokusiraju na savladavanje prepreke krvno-moždane i krvno-tumorske barijere te na ciljanu terapiju, lokalna terapija ostaje primarna linija liječenja. Odluka o izboru metode liječenja ovisi o broju i volumenu moždanih presadnica, njihovoj lokalizaciji, kliničkom statusu bolesnika, prethodno korištenim metodama liječenja, stadiju uznapredovalosti osnovne bolesti te prognozi bolesnika. U slučajevima kada aktivni pristup liječenju, koji uključuje operaciju i/ili radioterapiju, ne pridonosi kvaliteti života ili ukupnom preživljenju bolesnika, preporuča se najbolja potporna njega

MULTIPLE PRIMARY MALIGNANCIES

Multipli primarni tumori koji se javljaju kod istog bolesnika, metakrono ili sinkrono, relativno su rijedak događaj s porastom učestalosti posljednjih desetljeća. Cilj je ovog istraživanja utvrditi njihovu učestalost kod bolesnika liječenih hospitalno u Zavodu za radioterapijsku onkologiju Klinike za onkologiju Medicinskog fakulteta Sveučilišta u Zagrebu, KBC Zagreb u periodu od 2003. do 2009. godine. Učestalost je multiplih malignih tumora u navedenom periodu bila 2,4%. Od ukupno 103 bolesnika 97 je imalo dva, a 6 tri primarna tumora. Metakronih je tumora bilo 88, a sinkronih 20. Učestalost im je bila veća kod žena nego kod muškaraca, a i pojavljivali su se ranije kod žena nego kod muškaraca. Najčešće su kombinacije prvog i drugoga metakronog tumora kod muškaraca bile: rak prostate-maligni tumor probavnog sustava (osobito rak rektuma i debelog crijeva) i obrnutim redoslijedom te hematološke zloćudne bolesti-maligni tumor probavnog sustava; a kod žena: rak dojke-rak kontralateralne dojke i hematološke zloćudne bolesti (osobito ne-Hodgkinov limfom)-rak dojke. Valja očekivati da će učestalost bolesnika s višestrukim primarnim tumorima rasti, i zbog programa ranog otkrivanja tumora i zbog uspješnijeg liječenja i dužeg očekivanog trajanja života.Multiple primary malignancies, metachronous or synchronous, in a single patient are relatively rare event with the increase of incidence in recent decades. The aim of this research is to study their incidence in patients hospitalized at the Division of Radiotherapy, Department of Oncology, University of Zagreb, School of medicine, University Hospital Centre Zagreb from 2003 to 2009. The incidence of multiple primary malignancies was 2.4%. Among 103 patients, 97 had two, and 6 three primary tumors. Eighty-three cases were metachronous, while 20 cases were synchronous malignancies. The frequency was higher in females than males and their age at diagnosis of tumors was younger than in males. The most common tumor combinations in males were: prostate cancer-digestive system malignancy (especially colorectal cancer) and viceversa, and hematological malignant tumors-digestive system malignancy; while in women there were: breast cancer-cancer of contralateral breast and hematological malignant tumors (especially lymphoma non Hodgkin)-breast cancer. The incidence of multiple primary malignancies is expected to increase due to the better screening programs for early detection of malignancies as well as considerable improvement in their treatment and longer life expectancy

CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER

Rak dojke najčešća je maligna bolest u žena. Razvoj preventivnih mjera i dijagnostike i svih oblika liječenja (kirurgije, radioterapije, kemoterapije, hormonske i ciljane biološke terapije) doveo je do produljenja preživljenja i poboljšanja kvalitete života bolesnica. S ciljem optimalizacije i standardizacije liječenja, a slijedeći smjernice medicine temeljene na dokazima, donosimo smjernice za dijagnostiku, liječenje i praćenje bolesnica s rakom dojke koje su rezultat rada multidisciplinarnog tima stručnjaka.Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer

CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH INVASIVE BREAST CANCER

Rak dojke najčešća je maligna bolest u žena. Razvoj preventivnih mjera i dijagnostike i svih oblika liječenja (kirurgije, radioterapije, kemoterapije, hormonske i ciljane biološke terapije) doveo je do produljenja preživljenja i poboljšanja kvalitete života bolesnica. S ciljem optimalizacije i standardizacije liječenja, a slijedeći smjernice medicine temeljene na dokazima, donosimo smjernice za dijagnostiku, liječenje i praćenje bolesnica s rakom dojke koje su rezultat rada multidisciplinarnog tima stručnjaka.Breast cancer is the most common malignancy in women. Preventive measures, early diagnosis and development of all treatment modalities (surgery, radiotherapy, chemotherapy, hormonal and targeted biologic therapy) led to improvement in survival and quality of life of the patient. In order to standardize and optimize the approach, following good clinical practice standards, we bring consensus guidelines for diagnosis, treatment and monitoring of breast cancer patients as a result of consensus of a multidisciplinary team of experts for breast cancer