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Introduction: Decision making in surgical oncology of the breast has increased its complexity over the last twenty years. This Delphi survey investigates the opinion of an expert panel about the decision making process in surgical procedures on the breast for oncological purposes. Methods: Twenty-seven experts were invited to partake into a Delphi Survey. At the first round they have been asked to provide a list of features involved in the decision making process (patient's characteristics; disease characteristics; surgical techniques, outcomes) and comment on it. Using text-mining techniques we extracted a list of mono-bi-trigrams potentially representative of decision drivers. A technique of “natural language processing” called Word2vec was used to validate changes to texts using synonyms and plesionyms. Word2Vec was also used to test the semantic relevance of n-grams within a corpus of knowledge made up of books edited by panel members. The final list of variables extracted was submitted to the judgement of the panel for final validation at the second round of the Delphi using closed ended questions. Results: 52 features out of 59 have been approved by the panel. The overall consensus was 87.1% Conclusions: Text mining and natural language processing allowed the extraction of a number of decision drivers and outcomes as part of the decision making process in surgical oncology on the breast. This result was obtained transforming narrative texts into structured data. The high level of consensus among experts provided validation to this process.

Összefoglaló. Bevezetés: A komplementer és alternatív medicina (KAM) egyre népszerűbb a daganatos betegek körében világszerte. Az emlőrákkal diagnosztizált nők 45%-a használ KAM-ot, a fiatalabb betegek 62,5%-a. Magyarországon eddig egyetlen tanulmány jelent meg a témában, mely szerint a magyar, emlődaganattal küzdő nők 84,4%-a használ valamilyen komplementer terápiát. Egyes KAM-modalitások alkalmazása a gyógyszerkölcsönhatások miatt kockázatot hordoz. Fontos megismernünk a magyar páciensek igényeit és szokásait a KAM-használattal kapcsolatban, mely ismeret a klinikai gyakorlatban közvetlenül hasznosítható. Célkitűzés: Vizsgálatunk célja a magyar emlőrákos nők körében felmérni a KAM alkalmazásának mértékét, megvizsgálni ennek okait és az ezzel összefüggő demográfiai, pszichológiai és klinikai faktorokat. Módszer: Kérdőíves vizsgálatunkat az Országos Onkológiai Intézet Emlő- és Lágyrészsebészeti Osztályán végeztük az osztályon bent fekvők körében (n = 146). Felmértük a szociodemográfiai adatokat, a KAM-használat jellemzőit, a KAM iránti attitűdöt és az egészségkontroll-igényt. A kérdőív adatait klinikai adatokkal egészítettük ki. Eredmények: A válaszadók 36%-a felkeresett KAM-szolgáltatót, 71%-a használ KAM-készítményt, és 64%-a alkalmaz önsegítő gyakorlatot. Ezekről a betegek többsége egészségügyi szakembertől tájékozódik. A mintában a holisztikus szemlélet, valamint a belső és a társas külső kontroll dominál. A KAM-szolgáltatókat felkeresőknek és a KAM-készítményt alkalmazóknak erősebb a belsőkontroll-igényük. A KAM-szolgáltatást vagy önsegítő gyakorlatot alkalmazók kedvezőbben ítélik meg saját egészségi állapotukat. Következtetés: A betegeknek a számukra fontos személyektől, elsősorban a kezelőszemélyzettől kapott információ döntő az egészségükkel kapcsolatos viselkedésben, közöttük a KAM-választásban. Fontos látnunk a páciensek nagyfokú bizalmát az egészségügyi szakemberek iránt és erős igényét a KAM-mal kapcsolatos információk megbeszélésére, valamint az egészségük iránt érzett felelősségvállalásra és a kezelésben való aktív részvételre. Orv Hetil. 2022; 163(9): 350–361. Summary. Introduction: The popularity of complementary and alternative medicine (CAM) is increasing among cancer patients worldwide. 45% of women diagnosed with breast cancer use CAM, 62.5% of younger patients do so. So far, only one study has been published in Hungary, according to which 84.4% of Hungarian women with breast cancer use some form of complementary medicine. The utilization of some CAM modalities carries risks due to drug interactions. It is important to get to know the needs and habits of Hungarian patients in relation to CAM, which knowledge can be directly used in clinical practice. Objective: The aim of our study was to assess the extent of CAM utilization among Hungarian breast cancer patients, to examine the reasons behind this choice, and to see the relating/connecting demographic, psychological and clinical factors. Method: In a cross-sectional survey, a self-administered questionnaire was used among inpatients at the Department of Breast and Soft Tissue Surgery in the National Institute of Oncology (n = 146). We assessed socio-demographic data, characteristics of CAM use, attitudes toward CAM, and the need for health control. Clinical data were added to the questionnaire data. Results: 36% of the respondents visited some CAM providers, 71% used CAM preparation and 64% utilized self-help practices. Most patients are informed about these by a healthcare professional. The holistic approach is dominant in the sample as well as internal and social external control. Visitors to CAM providers and CAM preparation users have a stronger need for internal control. Visitors to CAM providers and self-help practitioners judge their own health status more favorable. Conclusion: The information that patients receive from people who are important to them, especially the caregiver, is crucial in their health-related behavior, including the choice of CAM. It is important to see such a high level of patient trust in health professionals and a strong need to discuss information about CAM, as well as a sense of responsibility for their health and active participation in treatment. Orv Hetil. 2022; 163(9): 350–361.

Összefoglaló. Bevezetés: A daganatellenes kezelések egy része gonadotoxikus hatású, ezért létrejött egy viszonylag új, interdiszciplináris terület, mely a fiatal onkológiai betegek termékenységének megőrzésével foglalkozik: ez a fertilitásprezerváció, más néven onkofertilitás. A nemzetközi irányelvek ellenére Magyarországon jelenleg nincs országos fertilitásprezervációs hálózat, a betegek irányítása és tájékoztatása nem szervezetten történik. Célkitűzés: Tanulmányunk célja, hogy felmérjük a hazánkban dolgozó onkológusok fertilitásprezervációval kapcsolatos ismereteit, és megismerjük azokat a tényezőket, amelyek a fiatal daganatos betegek termékenységmegőrzési programhoz való hozzáférését segíthetnék. Módszer: A Magyar Onkológus Társaság (MOT) tagjainak online kérdőívet küldtünk ki a fertilitásprezerváció témakörében 2020 novemberében. A felmérést 94 onkológus szakorvos töltötte ki teljes egészében, majd a beérkezett adatokat statisztikai módszerekkel elemeztük. Eredmények: A válaszoló magyar onkológusok többsége (77%) a daganatellenes kezelés fertilitásra gyakorolt hatását megbeszéli a páciensével, ténylegesen azonban csak kis számban kerülnek beutalásra a termékeny korban lévő páciensek. A válaszolók fele nyilatkozott úgy, hogy betegeit nem vagy csak ritkán irányítja tovább meddőségi centrumba; ennek hátterében a fertilitásprezervációs hálózat, a megfelelő képzés és a hazai irányelvek hiányát jelölik meg. A válaszadók többsége (86%) véli úgy, hogy az onkológus és meddőségi szakemberek szorosabb együttműködésének megszervezése szükségszerű Magyarországon. Következtetés: Tanulmányunk egy nemzeti onkofertilitás-hálózat létrehozásához szükséges teendők felmérésének első lépése. Eredményeink szerint szükséges a betegeket kezelő onkológusok és a fertilitásprezervációval foglalkozó reproduktív szakemberek közötti megfelelő együttműködés kialakítása, valamint az onkológus kollégák ismereteinek bővítése ezen a szakterületen. Orv Hetil. 2022; 163(6): 246–252. Summary. Introduction: Fertility preservation or oncofertility is a relatively new interdisciplinary field dealing with the preservation of female and male reproductive functions before the administration of gonadotoxic therapy. Despite recommendations from different international scientific bodies, Hungary still does not have a national fertility preservation network, patient referral is unorganised. Objective: As the first step towards establishing a national fertility preservation program, a study was designed to evaluate the Hungarian oncologists’ knowledge, attitudes and practice in the field of oncofertility. Method: A national online survey was sent to the physician members of the Hungarian Society of Clinical Oncology between November 2020 and February 2021. The survey was completed by 94 physicians and the results were analysed statistically. Results: The majority of the oncologists (77%) discusses reproductive health issues before starting gonadotoxic therapy. However, almost half of these physicians do not refer patients for fertility preservation consultation or treatment. Physicians report lack of organised fertility preservation network, lack of knowledge and clinical practice guidelines as major barriers in referring their patients for fertility preservation. The majority (86%) proposes that a better collaboration between cancer and fertility centers needs to be organized in Hungary. Conclusion: This study is the first nationwide survey to assess oncologists’ attitude, knowledge and practice in the field of oncofertility in Hungary. It highlights the need for more education and increased collaboration between oncologists and reproductive specialists. This is an important step towards the establishment of a national fertility preservation network which is our ultimate goal. Orv Hetil. 2022; 163(6): 246–252.

This is the first large-scale cross-country analysis of patients with chronic lymphocytic leukemia (CLL) aimed to evaluate the incidence, types, and key prognostic factors of secondary malignancies, and to assess the impact on overall survival based on retrospective claims data from three Central European countries. We analyzed 25,814 newly diagnosed CLL patients from Czechia, Hungary, and Poland; 10,312 (39.9%) patients were treated for CLL in study periods between 2004 and 2016. Out of the treated patients, 1986 (19.3%) received the FCR therapy in the first line and 779 (7.6%) received FCR in subsequent lines. We observed that 33.7% of treated patients developed secondary malignancies during the study. Based on country estimates, the probability to develop a secondary malignancy within 4 years since starting the first-line FCR therapy ranged between 28.0% and 36.8%. We found the age at diagnosis, male gender, any malignancy prior to the CLL diagnosis, and the CLL treatment to be the key risk factors for developing secondary malignancies. Specifically, the FCR therapy was a statistically significant (p 0.001) prognostic factor for risk increase with the hazard ratio between 1.46 and 1.60. Across the three Central European countries, we observed consistent results indicating FCR increased the risk of secondary malignancies in CLL patients. We conclude that secondary malignancies are clearly an undervalued burden for CLL patients, caregivers, and the healthcare system. When evaluating new therapies in regulatory and reimbursement decision making, the factor of secondary malignancies deserves deeper considerations.

Absztrakt: Bevezetés: A korszerű onkoplasztikus emlősebészet következményeként megjelenő jelentős emlőrekonstrukciós igény számos rendszerszintű kérdést vet fel. Vizsgálatra és szabályozásra várnak az onkoterápiák hatására és az idő múlásával bekövetkező esztétikai változások, illetve hosszú távú szövődmények miatti korrekciós műtétek indikációi; meghatározandó a helyreállító beavatkozások optimális és maximális száma, az elérni kívánt esztétikai végcél és az ezekhez szükséges emlősebészeti kapacitások, valamint finanszírozás. Célkitűzés: A jelen vizsgálat célja, hogy kérdőíves vizsgálattal felmérje a magyar emlőrákos populáció korszerű emlőrekonstrukciós igényeit és véleményét. Anyag és módszer: A vizsgálatba 500, mastectomián és azonnali vagy halasztott-azonnali emlőrekonstrukción átesett nőbeteg került bevonásra. Tizenegy kérdésből álló kérdőív segítségével történt az emlő rekonstrukciójához való ismereteknek és személyes viszonyulásnak, az esztétikai végeredménnyel és az ellátás szakmai színvonalával kapcsolatos elvárásoknak, továbbá az ellátórendszerrel és a finanszírozással kapcsolatos igényeknek a felmérése, majd elvégeztük az eredmények biostatisztikai elemzését. Eredmények: A betegek medián életkora 47 év (min.–max.: 26–73) volt, döntő részük (59%; n = 294) házas volt, és 52% (n = 260) rendelkezett egyetemi végzettséggel. A betegek 70%-a (n = 348) az emlő-helyreállítás eredményeként mezítelenül is nagyjából egyforma emlőket szeretett volna. Ehhez 43%-uk (n = 217) maximum kettő, 37%-uk (n = 184) maximum három-négy műtétet vállalna. A felmérésben részt vettek 44%-a (n = 220) szerint az egészségbiztosítónak három-négy rekonstrukciós beavatkozást kellene támogatnia. A betegek 86%-a (n = 430) a daganatos emlő korszerű sebészi kezelését speciálisan képzett emlősebészre bízná. Következtetés: Az emlőrák modern onkoplasztikus sebészi ellátása összetett, rendszerszintű kérdéseket vet fel. Az emlőrákos betegek jól képzett emlősebészeket szeretnének, akik az emlőrák korszerű sebészi kezelésén túl mastectomia esetén az egészségbiztosító által támogatott formában, maximum két műtéttel képesek magas esztétikai eredménnyel az emlők helyreállítására. Orv Hetil. 2020; 161(29): 1221–1228.

Absztrakt: Bevezetés és célkitűzés: A szerzők a Regnault „B” típusú emlőfelvarrás sebészi technikájának módosításával végzett onkoplasztikus műtéti technikát és az új emlősebészeti módszer alkalmazásához kapcsolódó retrospektív klinikopatológiai vizsgálat eredményeit mutatják be. Módszer: 2012. április és 2018. október között, emlőrák miatt, módosított Regnault „B” technikával operált 215 nőbeteg klinikopatológiai adatait prospektíven vezetett adatbázis alapján retrospektív módon vizsgáltuk. A betegek életminőségét validált kérdőív segítségével mértük fel, míg a műtétek esztétikai eredményét a szintén validált Breast Cancer Conservative Treatment (BCCT.core) számítógépes program és az 5 pontos Likert-skála alapján értékeltük. Eredmények: A betegek átlagéletkora 53 év (szórás: 29–81 év) volt. A medián utánkövetési idő 47 hónap (szórás: 7–85 hónap) volt. Az átlag műtéti idő 47 perc (szórás: 35–85 perc) volt, míg a patológiai tumorméret átlagosan 33 mm-nek (szórás: 18–58 mm) bizonyult. Pozitív sebészi szél miatt 13 (6%) esetben irányított reexcisióra, míg 3 (1,4%) esetben mastectomiára kényszerültünk. Az összesített szövődményarány 7,4% (n = 16) volt. Az esztétikai eredmények Likert-skála szerinti átlagértéke 4,2 (szórás: 2–5), míg a BCCT.core program alapján 1,3 pont (szórás: 1–4 pont) volt. Az életminőséggel kapcsolatos kérdőívek eredményei magas betegelégedettséget igazoltak. Következtetés: A módosított Regnault „B” emlőmegtartó technika biztonságos és hatékony standard ’level II.’ onkoplasztikus emlősebészeti technika. A műtét magas betegelégedettséggel, illetve kozmetikai eredménnyel képes a közepes vagy nagyobb térfogatú emlők külső, illetve külső-felső negyedeinek T1–T3-as tumorai miatt az emlők akár 20–50%-ának eltávolítására, majd egyidejű parenchymaáthelyezéssel történő rekonstrukciójára. A módszer előnye, hogy nem igényel ellenoldali szimmetrizációs műtétet, míg hátránya, hogy az emlő bőrpalástján vezetett metszések komplettáló mastectomia esetén az azonnali rekonstrukciót nehezítik. Orv Hetil. 2020; 161(24): 1002–1011.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for patients with chronic lymphocytic leukemia (CLL), despite extensive heterogeneity in this disease. To define the underlining regulatory dynamics, we analyze high-resolution time courses of ibrutinib treatment in patients with CLL, combining immune-phenotyping, single-cell transcriptome profiling, and chromatin mapping. We identify a consistent regulatory program starting with a sharp decrease of NF-κB binding in CLL cells, which is followed by reduced activity of lineage-defining transcription factors, erosion of CLL cell identity, and acquisition of a quiescence-like gene signature. We observe patient-to-patient variation in the speed of execution of this program, which we exploit to predict patient-specific dynamics in the response to ibrutinib based on the pre-treatment patient samples. In aggregate, our study describes time-dependent cellular, molecular, and regulatory effects for therapeutic inhibition of B cell receptor signaling in CLL, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring., Ibrutinib, a Bruton tyrosine kinase inhibitor, provides effective treatment for chronic lymphocytic leukemia (CLL). Here, the authors describe time-dependent molecular changes to malignant cells and to the immune system in patients undergoing ibrutinib therapy, with can be used for therapy monitoring.

The purpose of this study was to investigate the dose coverage of sentinel lymph nodes (SLN), level I, II and III axillary volumes from tangent fields for breast cancer patients with positive SLN without axillary dissection.In 30 patients with cN0 invasive breast cancer treated with breast conserving surgery and SLN biopsy, the SLN area was intraoperatively marked with a titanium clip. Retrospectively, the SLN area and axillary target volumes were contoured, and three plans [standard tangent fields (STgF), high tangent fields (HTgF), and STgF + axillary-supraclavicular field] were generated for each patient. The prescribed dose was standardized to 50 Gy in 2 Gy fractions to the isocenter.The mean dose with STgF or HTgF was 33.1 and 49.1 Gy (p = 0.0001) in the SLN area, 25.7 and 45.1 Gy (p0.0001) in the volume of level I, 7.2 and 28.9 Gy (p0.0001) in the level II and 3.5 and 12.7 Gy (p = 0.0003) in the level III. Adequate therapeutic doses to the level II or III volumes were delivered only with STgF + axillary-supraclavicular field. The mean dose of ipsilateral lung was the highest with the three-field-technique, 9.9 Gy. SLN area, level I, II or III were completely included in the HTgF with 93.3%, 73.3%, 13.3% and 0%, respectively.SLN area should be marked by surgical clip and axillary target volumes should be contoured to obtain accurate dose estimations. The use of HTgF improve axillary coverage.

Introduction Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). Methods Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin p < 0.001). There were significantly more re-excisions due to R1 (“ink on tumor”) in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI.

Significance Basal-like breast cancers (BLBC) have poor prognosis. Here, we present evidence that reprogrammed transsulfuration is a hallmark of BLBC. Human BLBC tumors exhibit elevated levels of cystathione β-synthetase (CBS) but diminished expressions of oxidative Cys-catabolizing enzymes supporting a Cys-addicted phenotype. We demonstrated that in BLBC cells, CBS plays a role in cellular proliferation and invasiveness, HIF1-α activation under hypoxia, and protection against oxidative stress and CySSCy deprivation–induced ferroptosis. Tumor progression and angiogenesis was impaired in shCBS xenograft tumors, which had larger intratumoral necrotic areas. Mechanistic analyses largely based on sulfur metabolome and proteomics data revealed that realigned Cys persulfidation is a determining factor in this Cys-addicted phenotype of BLBC tumors, which holds promise for drug development., Basal-like breast cancer (BLBC) is the most aggressive subtype of breast tumors with poor prognosis and limited molecular-targeted therapy options. We show that BLBC cells have a high Cys demand and reprogrammed Cys metabolism. Patient-derived BLBC tumors from four different cohorts exhibited elevated expression of the transsulfuration enzyme cystathione β-synthetase (CBS). CBS silencing (shCBS) made BLBC cells less invasive, proliferate slower, more vulnerable to oxidative stress and cystine (CySSCy) deprivation, prone to ferroptosis, and less responsive to HIF1-α activation under hypoxia. shCBS xenograft tumors grew slower than controls and exhibited impaired angiogenesis and larger necrotic areas. Sulfur metabolite profiling suggested that realigned sulfide/persulfide-inducing functions of CBS are important in BLBC tumor progression. Supporting this, the exclusion of serine, a substrate of CBS for producing Cys but not for producing sulfide/persulfide, did not exacerbate CySSCy deprivation–induced ferroptosis in shCBS BLBC cells. Impaired Tyr phosphorylation was detected in shCBS cells and xenografts, likely due to persulfidation-inhibited phosphatase functions. Overexpression of cystathione γ-lyase (CSE), which can also contribute to cellular sulfide/persulfide production, compensated for the loss of CBS activities, and treatment of shCBS xenografts with a CSE inhibitor further blocked tumor growth. Glutathione and protein-Cys levels were not diminished in shCBS cells or xenografts, but levels of Cys persulfidation and the persulfide-catabolizing enzyme ETHE1 were suppressed. Finally, expression of enzymes of the oxidizing Cys catabolism pathway was diminished, but expression of the persulfide-producing CARS2 was elevated in human BLBC tumors. Hence, the persulfide-producing pathways are major targetable determinants of BLBC pathology that could be therapeutically exploited.

Összefoglaló. Bevezetés: A komplementer és alternatív medicina (KAM) egyre népszerűbb a daganatos betegek körében világszerte. Az emlőrákkal diagnosztizált nők 45%-a használ KAM-ot, a fiatalabb betegek 62,5%-a. Magyarországon eddig egyetlen tanulmány jelent meg a témában, mely szerint a magyar, emlődaganattal küzdő nők 84,4%-a használ valamilyen komplementer terápiát. Egyes KAM-modalitások alkalmazása a gyógyszerkölcsönhatások miatt kockázatot hordoz. Fontos megismernünk a magyar páciensek igényeit és szokásait a KAM-használattal kapcsolatban, mely ismeret a klinikai gyakorlatban közvetlenül hasznosítható. Célkitűzés: Vizsgálatunk célja a magyar emlőrákos nők körében felmérni a KAM alkalmazásának mértékét, megvizsgálni ennek okait és az ezzel összefüggő demográfiai, pszichológiai és klinikai faktorokat. Módszer: Kérdőíves vizsgálatunkat az Országos Onkológiai Intézet Emlő- és Lágyrészsebészeti Osztályán végeztük az osztályon bent fekvők körében (n = 146). Felmértük a szociodemográfiai adatokat, a KAM-használat jellemzőit, a KAM iránti attitűdöt és az egészségkontroll-igényt. A kérdőív adatait klinikai adatokkal egészítettük ki. Eredmények: A válaszadók 36%-a felkeresett KAM-szolgáltatót, 71%-a használ KAM-készítményt, és 64%-a alkalmaz önsegítő gyakorlatot. Ezekről a betegek többsége egészségügyi szakembertől tájékozódik. A mintában a holisztikus szemlélet, valamint a belső és a társas külső kontroll dominál. A KAM-szolgáltatókat felkeresőknek és a KAM-készítményt alkalmazóknak erősebb a belsőkontroll-igényük. A KAM-szolgáltatást vagy önsegítő gyakorlatot alkalmazók kedvezőbben ítélik meg saját egészségi állapotukat. Következtetés: A betegeknek a számukra fontos személyektől, elsősorban a kezelőszemélyzettől kapott információ döntő az egészségükkel kapcsolatos viselkedésben, közöttük a KAM-választásban. Fontos látnunk a páciensek nagyfokú bizalmát az egészségügyi szakemberek iránt és erős igényét a KAM-mal kapcsolatos információk megbeszélésére, valamint az egészségük iránt érzett felelősségvállalásra és a kezelésben való aktív részvételre. Orv Hetil. 2022; 163(9): 350-361.The popularity of complementary and alternative medicine (CAM) is increasing among cancer patients worldwide. 45% of women diagnosed with breast cancer use CAM, 62.5% of younger patients do so. So far, only one study has been published in Hungary, according to which 84.4% of Hungarian women with breast cancer use some form of complementary medicine. The utilization of some CAM modalities carries risks due to drug interactions. It is important to get to know the needs and habits of Hungarian patients in relation to CAM, which knowledge can be directly used in clinical practice.The aim of our study was to assess the extent of CAM utilization among Hungarian breast cancer patients, to examine the reasons behind this choice, and to see the relating/connecting demographic, psychological and clinical factors.In a cross-sectional survey, a self-administered questionnaire was used among inpatients at the Department of Breast and Soft Tissue Surgery in the National Institute of Oncology (n = 146). We assessed socio-demographic data, characteristics of CAM use, attitudes toward CAM, and the need for health control. Clinical data were added to the questionnaire data.36% of the respondents visited some CAM providers, 71% used CAM preparation and 64% utilized self-help practices. Most patients are informed about these by a healthcare professional. The holistic approach is dominant in the sample as well as internal and social external control. Visitors to CAM providers and CAM preparation users have a stronger need for internal control. Visitors to CAM providers and self-help practitioners judge their own health status more favorable.The information that patients receive from people who are important to them, especially the caregiver, is crucial in their health-related behavior, including the choice of CAM. It is important to see such a high level of patient trust in health professionals and a strong need to discuss information about CAM, as well as a sense of responsibility for their health and active participation in treatment. Orv Hetil. 2022; 163(9): 350-361.

Introduction: Fertility preservation or oncofertility is a relatively new interdisciplinary field dealing with the preservation of female and male reproductive functions before the administration of gonadotoxic therapy. Despite recommendations from different international scientific bodies, Hungary still does not have a national fertility preservation network, patient referral is unorganised. Objective: As the first step towards establishing a national fertility preservation program, a study was designed to evaluate the Hungarian oncologists' knowledge, attitudes and practice in the field of oncofertility. Method: A national online survey was sent to the physician members of the Hungarian Society of Clinical Oncology between November 2020 and February 2021. The survey was completed by 94 physicians and the results were analysed statistically. Results: The majority of the oncologists (77%) discusses reproductive health issues before starting gonadotoxic therapy. However, almost half of these physicians do not refer patients for fertility preservation consultation or treatment. Physicians report lack of organised fertility preservation network, lack of knowledge and clinical practice guidelines as major barriers in referring their patients for fertility preservation. The majority (86%) proposes that a better col-laboration between cancer and fertility centers needs to be organized in Hungary. Conclusion: This study is the first nationwide survey to assess oncologists' attitude, knowledge and practice in the field of oncofertility in Hungary. It highlights the need for more education and increased collaboration between oncologists and reproductive specialists. This is an important step towards the establishment of a national fertility preservation network which is our ultimate goal.Összefoglaló. Bevezetés: A daganatellenes kezelések egy része gonadotoxikus hatású, ezért létrejött egy viszonylag új, interdiszciplináris terület, mely a fiatal onkológiai betegek termékenységének megőrzésével foglalkozik: ez a fertilitásprezerváció, más néven onkofertilitás. A nemzetközi irányelvek ellenére Magyarországon jelenleg nincs országos fertilitásprezervációs hálózat, a betegek irányítása és tájékoztatása nem szervezetten történik. Célkitűzés: Tanulmányunk célja, hogy felmérjük a hazánkban dolgozó onkológusok fertilitásprezervációval kapcsolatos ismereteit, és megismerjük azokat a tényezőket, amelyek a fiatal daganatos betegek termékenységmegőrzési programhoz való hozzáférését segíthetnék. Módszer: A Magyar Onkológus Társaság (MOT) tagjainak online kérdőívet küldtünk ki a fertilitásprezerváció témakörében 2020 novemberében. A felmérést 94 onkológus szakorvos töltötte ki teljes egészében, majd a beérkezett adatokat statisztikai módszerekkel elemeztük. Eredmények: A válaszoló magyar onkológusok többsége (77%) a daganatellenes kezelés fertilitásra gyakorolt hatását megbeszéli a páciensével, ténylegesen azonban csak kis számban kerülnek beutalásra a termékeny korban lévő páciensek. A válaszolók fele nyilatkozott úgy, hogy betegeit nem vagy csak ritkán irányítja tovább meddőségi centrumba; ennek hátterében a fertilitásprezervációs hálózat, a megfelelő képzés és a hazai irányelvek hiányát jelölik meg. A válaszadók többsége (86%) véli úgy, hogy az onkológus és meddőségi szakemberek szorosabb együttműködésének megszervezése szükségszerű Magyarországon. Következtetés: Tanulmányunk egy nemzeti onkofertilitás-hálózat létrehozásához szükséges teendők felmérésének első lépése. Eredményeink szerint szükséges a betegeket kezelő onkológusok és a fertilitásprezervációval foglalkozó reproduktív szakemberek közötti megfelelő együttműködés kialakítása, valamint az onkológus kollégák ismereteinek bővítése ezen a szakterületen. Orv Hetil. 2022; 163(6): 246–252.

Involving 207 breast cancer patients a retrospective study was performed to facilitate the acceptance of the central pedicled, modified Wise-pattern therapeutic mammoplasty technique as a standard volume-displacement level II oncoplastic breast-conserving surgery (OBCS). The overall local recurrence rate was 5.8% with an average follow-up of 43.9 months. The median time to the initiation of the adjuvant treatment was 4.9 weeks. Due to positive surgical margins, 13 (6.84%) completional surgeries were performed. In total, 45 complications (12.9%) were recorded. The median values of the esthetic outcomes represented improved cosmetic results. The modified Wise-pattern technique could be a standard, safe and repeatable level II volume-displacement OBCS.

Background This study presents a novel Level I oncoplastic breast-conserving surgery technique for performing tumorectomy by retroglandular exploration through a skin incision made in the inferior mammary fold. Patients and Methods A retrospective single-center cohort study involving patients with early-stage breast cancer (n = 102) was performed. The patient characteristics were recorded, as well as the quality of life rated by BREAST-Q. Postoperative complications were assessed using the Clavien-Dindo classification system. Esthetic outcomes were evaluated with Breast Cancer Conservative Treatment-cosmetic results (BCCT.core) software and a 5-point Likert scale. Results The median follow-up time was 11 months (range, 7-25 months). The median specimen weight and operative time were 49.8 g (range, 13.4-117.9 g) and 40 minutes (range, 20-80 minutes), respectively. The mean pathologic tumor size was 15 mm (SD, ±7). Owing to positive surgical margins, re-excisions and mastectomies were performed in 13.7% and 2.9% of patients, respectively. The overall complication rate was 24.5% (n = 25), with the most common being seroma formation (13.7%; n = 14). The median Likert scale score was 4.3 (range, 2.1-5), and the median overall esthetic outcome assessed by BCCT.core was 2.1 points (range, 1-4 points). In BREAST-Q domains, the median scores of the “adverse effects of radiation,” “physical well-being,” the “satisfaction with breasts,” and the “psychosocial well-being” were 27, 35, 90, and 93, respectively. Conclusion Retroglandular oncoplastic breast-conserving surgery is a novel, effective Level I oncoplastic technique for radical resection of breast tumors ≤ 3 cm in size. Additional advantages include the preservation of natural breast shape, the safety of the technique, and the lack of a need for contralateral symmetrization.

Simple Summary Sentinel lymph node (SLN) status is still the most important prognostic factor for melanoma patients; however, the efficacy of completing lymph node dissection remains questionable. The aim of our study was to assess the correlation between known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, and SLN status. Statistical analysis revealed that Breslow thickness was associated with SLN status; however, neither NRAS nor BRAF showed a predictive value. Furthermore, NRAS mutation in primary tumors proved to be an independent factor of tumor progression. This suggests that regardless of the SLN status, the NRAS-mutant subgroup of patients requires closer monitoring. Abstract Purpose: To assess the prognostic role of sentinel lymph node status (SLN) in melanoma patients, a statistical comparison was performed with the application of already known prognostic factors, mutational occurrence of BRAF and NRAS in the primary tumor, as well as disease outcome. Methods: Our retrospective single-center study involved 159 melanoma cases, who underwent SLN biopsy. The following clinico-pathological data were collected: age, gender, location of primary tumor, Breslow thickness, ulceration degree, histological subtype, mitosis count, lymphovascular and perineural invasion, presence of tumor-infiltrating lymphocytes, regression signs, mutations of BRAF and NRAS of the primary tumors, and SLN status. Results: From the studied clinico-pathological factors, only Breslow thickness increased the risk of SLN positivity (p = 0.025) by multivariate analysis, while neither BRAF nor NRAS mutation of the primary tumor proved to be a predictor of the SLN status. While the NRAS-mutant subgroup showed the most unfavorable outcome for progression-free and distant metastasis-free survival, their rate of positive SLNs proved to be relatively lower than that of patient groups with BRAF mutation and double-wild-type phenotypes. Conclusion: Similarly to the importance of SLN positivity, NRAS mutation of the primary tumor proved to be an independent prognostic factor of progression. Therefore, despite negative SLN, this NRAS-mutant subgroup of patients still requires closer monitoring to detect disease progression.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL). Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance. To assess the correlation between disease progression, and the emergence and temporal dynamics of the most common resistance mutation BTK

In recent years some serologic parameters emerged as potential prognostic factors. The neutrophil-to-lymphocyte ratio (NLR) has the most evidence; however, other serologic factors were also reported. The only established systemic treatment in triple-negative breast cancer (TNBC) is chemotherapy which is preoperatively applied more widely. For these patients few data are available on which serologic markers would be the best predictor for disease-free (DFS) and overall survival (OS). Data of 137 TNBC patients treated (2005-2016) with neoadjuvant chemotherapy at our center were analyzed. Beyond pathological factors, white blood cell (WBC), neutrophil (NE), lymphocyte (LY) and platelet (PL) counts, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) were investigated. In univariate analysis, most parameters (NE1, LY1, NLR1, PLR1, SII1) measured at baseline and before the third cycle (NE3, LY3, etc.) of chemotherapy showed significant association with survival. After the exclusion of correlated variables, in multivariate analysis NLR1, Ki67 and pathological stage were independent predictors of DFS and OS. In an exploratory analysis new markers were found: dichotomization by NLR1xNLR3 and PL1/(PL3)2 resulted in significantly different DFS of patients with low and high NLR1, respectively. A high PL3xLY3 level was an exclusive marker of relapse after pathological complete remission.

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL). Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance. To assess the correlation between disease progression, and the emergence and temporal dynamics of the most common resistance mutation BTKC481S , sensitive (10-4 ) time-resolved screening was performed in 83 relapsed/refractory CLL patients during single-agent ibrutinib treatment. With a median follow-up time of 40 months, BTKC481S was detected in 48·2% (40/83) of the patients, with 80·0% (32/40) of them showing disease progression during the examined period. In these 32 cases, representing 72·7% (32/44) of all patients experiencing relapse, emergence of the BTKC481S mutation preceded the symptoms of clinical relapse with a median of nine months. Subsequent Bcl-2 inhibition therapy applied in 28/32 patients harbouring BTKC481S and progressing on ibrutinib conferred clinical and molecular remission across the patients. Our study demonstrates the clinical value of sensitive BTKC481S monitoring with the largest longitudinally analysed real-world patient cohort reported to date and validates the feasibility of an early prediction of relapse in the majority of ibrutinib-treated relapsed/refractory CLL patients experiencing disease progression.

Richter syndrome (RS) represents the development of high-grade lymphoma in patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) and presents a diagnostic and therapeutic challenge with an adverse prognosis. The genetic background and morphology of RS in CLL patients treated with chemoimmunotherapy is extensively characterised; however, our knowledge about RS in patients treated with targeted oral therapies should be extended. To understand the morphologic and molecular changes leading to RS in CLL patients treated with the Bruton's tyrosine kinase inhibitor, ibrutinib, and the BCL2 inhibitor, venetoclax, sequential samples from six CLL/SLL patients undergoing RS were collected in both the CLL and RS phases. A detailed immunophenotypic analysis of formalin-fixed, paraffin-embedded tissue specimens of RS phase was performed, followed by extensive molecular characterisation of CLL and RS samples, including the immunoglobulin heavy chain gene (IGH) rearrangement, TP53 mutations, drug-induced resistance mutations in BTK and BCL2 genes and various copy number changes and point mutations detectable with multiplex ligation-dependent probe amplification (MLPA). Rare, non-diffuse large B-cell lymphoma phenotypes of RS were observed in 3/6 cases, including plasmablastic lymphoma and a transitory entity between diffuse large B-cell lymphoma and classical Hodgkin lymphoma. The majority of cases were clonally related and harboured an unmutated variable region of the immunoglobulin heavy chain gene. Abnormalities affecting the TP53 gene occurred in all patients, and every patient carried at least one genetic abnormality conferring susceptibility to RS. In the background of RS, 2/5 patients treated with ibrutinib showed a BTK C481S resistance mutation. One patient developed a BCL2 G101V mutation leading to venetoclax resistance and RS. In conclusion, our findings contribute to better understanding of RS pathogenesis in the era of targeted oral therapies. Rare phenotypic variants of RS do occur under the treatment of ibrutinib or venetoclax, and genetic factors leading to RS are similar to those identified in patients treated with chemoimmunotherapy. To our best knowledge, we have reported the first BCL2 G101V mutation in an RS patient treated with venetoclax.

The surgical treatment is still the most effective method in curing of early breast cancer. Breast preservation and the application of oncoplastic principles became generally accepted, the sentinel lymph node biopsy in the surgical treatment of the axilla is primary, and the indication for axillary block dissection (ABD) is narrowing further. The neoadjuvant oncological treatment that is applied more and more widely presented surgery with new challenges. Hereunder we summarise our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.

The significant need for breast reconstruction resulting from the spread of oncoplastic breast surgery raises a number of systemic issues. Clarification and regulation of the indications are needed for aesthetic changes of the reconstructed breast due to oncotherapy treatments, ageing and technical problems of implants; a number of operations, targeted aesthetic goals as well as surgical capacities and financial background should also be determined.Our aim was to conduct a survey on the opinions and needs of the Hungarian breast cancer population about a modern breast reconstruction system.A study was conducted enrolling 500 patients who underwent mastectomy with immediate or delayed reconstruction. A structured questionnaire containing eleven questions was used to measure the attitude for loss and reconstruction of breast, the expectation of cosmetic outcome and qualification of the operating surgeon and the needs relating to the health system and funding.The median age was 47 years (min.-max.: 26-73), 59% (n = 294) was married and 52% (n = 260) had graduated in university. The majority of women (70%; n = 348) would like to have nakedly also similar breasts after the reconstruction process. To achieve this, 43% (n = 217) and 37% (n = 184) would undergo maximum two or four procedures, respectively, supported by the national health insurance company. 86% (n = 430) would like to choose qualified breast surgeon for her treatment.The modern oncoplastic treatment raises complex, systemic issues. Women with breast cancer would like to have qualified breast surgeons restoring their breasts by two operations, all funded by the national health insurance company. Orv Hetil. 2020; 161(29): 1221-1228.

This study aimed to describe the modified Regnault "B" oncoplastic technique as a standard volume-displacement level II oncoplastic breast-conserving surgery and the related clinicopathological study.A retrospective, single-centre study was performed between April 2012 and October 2018 involving 215 breast-cancer patients. Patient characteristics and postoperative complications were recorded, and the quality of life was rated by questionnaires. Aesthetic outcomes were evaluated with BCCT.core software and a five-point Likert scale.The mean patient age was 53 years (range: 29-81 years), with a median follow-up of 47 months (range: 7-85 months). The average surgery time was 47 min (range: 35-85 min) and the pathological average size of the tumours was 33 mm (range: 18-58 mm). Due to positive surgical margins, 13 (6%) completion re-excisions and 3 (1.4%) mastectomies were performed. In total, 16 complications (7.4%) were recorded. The median Likert scale score was 4.2, and the median overall aesthetic outcome assessed by BCCT.core was 1.3 points. According to the quality of life questionnaire, average points of the results demonstrated a high level of patient satisfaction.In medium- to large-breasted patients, the modified Regnault "B" technique is a safe and repeatable level II volume-displacement oncoplastic breast-conservation technique. This technique allows extended removal (20-50% of breast tissue) of T1-T3 tumours from the upper outer quadrant and the border of outer quadrants of the breast with improved aesthetic results. The advantage of this technique is that contralateral symmetrisation is not required, while disadvantage of this technique is the skin incision on the breast skin envelope that can make some difficulties when completion mastectomy is required with immediate reconstruction. Orv Hetil. 2020; 161(24): 1002-1011.

The reconstruction of the nipple–areola complex (NAC) following breast reconstruction significantly improves the cosmetic result and enables the visual transformation of the newly created breast mound into the breast as an organ (Shestak, Revision of nipple areola reconstruction. In: Reoperative plastic surgery of the breast. Lippincott Williams & Wilkins, 2006). The NAC is generally performed as a second-stage procedure under local anaesthesia in a sterile operating theatre, often in combination with other minor revisions like lipomodelling or scar corrections. Accurate planning and mark-up is mandatory for bilateral symmetry of the NAC. In terms of timing, nipple reconstruction optimally has to allow the gravitational settling of the reconstructed breast mound (Shestak, Revision of nipple areola reconstruction. In: Reoperative plastic surgery of the breast. Lippincott Williams & Wilkins, 2006). The most popular techniques for nipple reconstruction combine local random skin flaps, sometimes composite flaps, with costochondral cartilage with tattooing procedure. These techniques are able to offer high level patient satisfaction. Problems mostly associated with nipple reconstruction include asymmetric bilateral nipple position, loss of nipple projection and partial or total nipple necrosis (Shestak, Revision of nipple areola reconstruction. In: Reoperative plastic surgery of the breast. Lippincott Williams & Wilkins, 2006).

Abstract: Introduction and aim: To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. Method: Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4–24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1–2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan–Meier method. Late side effects and cosmetic results were also registered. Results: The median follow-up time following the second breast conserving therapy was 61 months (range: 26–189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. Conclusion: Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430–438.

Background Acellular dermal matrices have been used for direct-to-implant (DTI) breast reconstruction (BR), eliminating the load of the lower pole skin envelope. However, the available allograft matrices add considerable health care costs. This study examined the long-term follow-up of synthetic ULTRAPRO ® mesh as a low-cost potential alternative to biological matrices. Patients and methods A retrospective cohort study was performed between January 2013 and January 2016, involved 112 early-stage breast cancer and/or BRCA 1/2 patients, and evaluated 189 immediate DTI BRs following skin-, areola- or nipple-sparing mastectomy using ULTRAPRO ® mesh. Patient characteristics and postoperative complications were recorded, and quality of life was rated by the patients using the EORTC-QLQ-C30-BR23 questionnaire. Aesthetic outcomes and palpability of the implants were evaluated by four breast surgeons on a 5-point Likert scale. All recorded parameters were statistically analysed. Results Ten patients were lost-to-follow-up, resulting in 102 patients and 174 breast surgery cases analysed. The mean age was 43 years, with 23.4 months of follow-up on average. Forty-six patients (45.1%) had previous radiotherapy with pre-existing scars. In total, 32 complications (18.3%) were recorded, including 12 minor (6.9%) and 20 major (11.4%) complications requiring revision. All median quality of life scores were above 83 points, representing a high score, with an average 4-point rating for the aesthetic outcome and natural consistency of the breast. Conclusion Partially absorbable ULTRAPRO ® mesh could be used successfully in DTI BR, offering a safe, less expensive alternative to biological matrices. Adequate indications and patient selection are necessary.

Introduction The National Institute of Oncology, Budapest conducted a single centre randomized clinical study. The OTOASOR (Optimal Treatment Of the Axilla – Surgery Or Radiotherapy) trial compares completion of axillary lymph node dissection (cALND) to regional nodal irradiation (RNI) in patients with sentinel lymph node metastasis (pN1sn) in stage I–II breast cancer. Patients and methods Patients with primary invasive breast cancer (cN0 and cT ≤ 3 cm) were randomized before surgery for cALND (standard treatment) or RNI (investigational treatment). Sentinel lymph nodes (SN) were investigated with serial sectioning at 0.5 mm levels by hematoxylin–eosin staining. Investigational treatment arm patients received 50 Gy RNI instead of cALND. Adjuvant treatment and follow up were performed according to the actual guidelines. Between August 2002 and June 2009, 1054 patients were randomized for cALND and 1052 patients for RNI. SN was evaluated in 2073 patients and was positive in 526 patients (25.4%). 474 cases were evaluable (244 in the cALND and 230 in the RNI arm), and in the cALND group 94 of 244 patients (38.5%) who underwent completion axillary surgery has additional positive nodes. The two arms were well balanced according to the majority of main prognostic factors. Primary endpoint was axillary recurrence and secondary endpoints were overall survival (OS) and disease-free survival (DFS). Results Mean follow-up was 97 months (Q1–Q3: 80–120). Axillary recurrence was 2.0% in cALND arm vs. 1.7% in RNI arm (p = 1.00). OS at 8 years was 77.9% vs. 84.8% (p = 0.060), and DFS was 72.1% in cALND arm and 77.4% after RNI (p = 0.51). The results show that RNI is statistically not inferior to cALND treatment. Conclusions The long term follow-up results of this prospective-randomized trial suggest that RNI without cALND does not increase the risk of axillary failure in selected patients with early-stage invasive breast cancer (cT ≤ 3 cm, cN0) and pN1(sn). Axillary radiotherapy should be an alternative treatment for selected patients with sentinel lymph node metastases.

Abstract: Introduction: In recent years much progress has been made in the therapy of chronic lymphocytic leukaemia, as the new innovative medicine proved to be effective in managing patients carrying TP53 abnormalities. To identify all these patients, it is essential to screen for both forms of TP53 defects, including both 17p deletions and TP53 mutations. Aim: The aim of this study was to determine the frequency of TP53 mutations and their association with 17p deletions in a large Hungarian cohort of 196 patients suffering from chronic lymphocytic leukaemia. Method: We performed mutation analysis of TP53 (exons 3–10) using Sanger sequencing. Results: TP53 mutations were present in 15.8% of patients, half of which were associated with 17p deletion. By analysing both forms, TP53 defect was identified in 25.4% of the patients. Conclusions: Our study demonstrates that by performing a TP53 mutation analysis, an additional 10% of high-risk patients can be detected. Orv. Hetil., 2017, 158(6), 220–228.

Background Breast cancer diagnosed in very young women (VYWBC; ≤35 years) and young women (YWBC; 36–45 years) tends to be heterogeneous. The current study aimed to compare the clinicopathological characteristics and long-term clinical outcomes between YWBC and VYWBC subgroups. Patients and methods The institutional prospectively led database was retrospectively analysed from 2000 to 2014 at the National Institute of Oncology, Hungary. A total of 297 patients were assigned to the VYWBC group, and 301 patients were assigned to the YWBC group. Results The median follow-up period was 69 months for the VYWBC group and 79 months for the YWBC group. Significant differences were observed based on breast cancer subtype. The proportion of Triple-negative and ER-negative patients was higher in the VYWBC group than in the YWBC group (P = 0.00008). The incidence of distant metastasis was significantly higher in the VYWBC group (P = 0.01). Significant differences in the frequency of chemotherapy (P = 0.049) and endocrine therapy (P = 0.037) were observed between the two groups. The YWBC group exhibited significantly better overall survival (OS) and disease-free survival (DFS) rates than did the VYWBC group (P = 0.00005 and P = 0.00004, respectively). Conclusion Breast cancers in VYWBC are biologically different from those in YWBC and tend to be more aggressive. Younger age was associated with worse OS and DFS. Young women with breast cancer should be subgrouped into VYWBC and YWBC populations, and these subgroups should be targeted by specialized clinical trials and further investigations.

Chronic lymphocytic leukemia (CLL) is a genetically, epigenetically, and clinically heterogeneous disease. Despite this heterogeneity, the Bruton tyrosine kinase (BTK) inhibitor ibrutinib provides effective treatment for the vast majority of CLL patients. To define the underlining regulatory program, we analyzed high-resolution time courses of ibrutinib treatment in closely monitored patients, combining cellular phenotyping (flow cytometry), single-cell transcriptome profiling (scRNA-seq), and chromatin mapping (ATAC-seq). We identified a consistent regulatory program shared across all patients, which was further validated by an independent CLL cohort. In CLL cells, this program starts with a sharp decrease of NF-κB binding, followed by reduced regulatory activity of lineage-defining transcription factors (including PAX5 and IRF4) and erosion of CLL cell identity, finally leading to the acquisition of a quiescence-like gene signature which was shared across several immune cell types. Nevertheless, we observed patient-to-patient variation in the speed of its execution, which we exploited to predict patient-specific dynamics in the response to ibrutinib based on pre-treatment samples. In aggregate, our study describes the cellular, molecular, and regulatory effects of therapeutic B cell receptor inhibition in CLL at high temporal resolution, and it establishes a broadly applicable method for epigenome/transcriptome-based treatment monitoring.

Background The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin- and nipple-sparing mastectomy (SSM/NSM) for breast cancer (BC) treatment or prevention. Immediate breast reconstruction is based on implants or autologous tissue. The optimal positioning of the implant is not clear: While pre-pectoral positioning respects the anatomic position of the mammary gland and avoids surgery-induced alterations of the pectoralis major muscle, the lack of muscle coverage may increase the risk of additional surgical interventions due to major complications. The Oncoplastic Breast Consortium (OPBC) identified this knowledge gap as research priority in 2019. Trial design International, multicenter study with a superiority trial design and two parallel groups with 1:1 random allocation to pre- or sub-pectoral implant-based breast reconstruction (IBBR). Following a pragmatic approach, randomly assigned IBBR will be performed according to the surgeons’ usual care by use of a one- or two-stage approach with or without adjunctive mesh. Follow-up visits are performed within routine care (visits at 10 days and at 1, 6, 12, 18 and 24 months after surgery). Oncological follow-up will be conducted annually for 10 years. ClinicalTrials.gov identifier: NCT04293146. Eligibility We include women ≥ 18 years, with an indication for NSM or SSM and IBBR in the therapeutic or risk-reducing setting, the ability to complete QoL questionnaires and the adequateness of skin flap(s) for pre-pectoral IBBR (intraoperative decision of the surgeon). Specific aims The primary objective is to test whether pre-pectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being of the chest (BREAST-Q) compared to sub-pectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of BC. Secondary endpoints include loss of expander or implant, complications, other BREAST-Q QoL and patient satisfaction domains, aesthetic outcomes and recurrence free survival. Interference of different dose distributions of radiation therapy and its consequences on the distribution of local tumor recurrences will be assessed. Statistical methods The primary analysis will be performed on the full analysis set following the intention-to-treat principle. To test the primary hypothesis, a linear mixed model will be fitted with the BREAST-Q score as response variable and treatment assignment as independent variable. The analysis will be adjusted for baseline BREAST-Q score, stratification factors (i.e. uni- vs bilateral surgery and NSM vs SSM) and other potential confounders. A random intercept to account for the center effect will be included. As a sensitivity analysis, an unadjusted t-test will be performed on the BREAST-Q score change from baseline to compare the two treatment arms. The sample size was determined for the primary endpoint, with an expected mean score of 76 points for sub-pectoral and 80 points for pre-pectoral implants. The clinically relevant difference to be detected in this superiority design is 4 points, with an expected common standard deviation of 13 points. A sample size of 334 patients provides an 80% power for a two-sided t-test at level α = 0.05. Compensating for a 10% dropout rate, the total sample size was calculated to include 372 patients. Present accrual and target accrual By June 2020, one study site (Basel) has been initiated. During a 21-month recruitment period, we plan to include 372 patients at 21 sites in Switzerland, USA, China, Austria, Germany, Hungary and Sweden. Contact information Prof. Dr. Walter Paul Weber, Chefarzt Brustchirurgie, Breast Surgeon SSO, Universitätsspital Basel, Spitalstrasse 21, CH-4031 Basel, Tel: +41 61 328 61 49, Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Elisabeth A Kappos, Meredith M Regan, Giusi Moffa, Yves Harder, Karin Ribi, Shelley Potter, Andrea Pusic, Mathias K Fehr, Lars G Hemkens, Thomas Holzbach, Jian Farhadi, Colin Simonson, Michael Knauer, Ralph Verstappen, Heiner Bucher, Daniel Zwahlen, Frank Zimmermann, Matthias Schwenkglenks, Rosine Mucklow, Vesna Bjelic-Radisic, Amelia Chiorescu, Yoon Chun, Subrina Farah, Xiasong Chen, Linda Nigard, Sherko Kümmel, Roland Reitsamer, Maik Hauschild, Ilario Fulco, Christoph Tausch, Thomas Fischer, Dimitri Sarlos, Mihai Constantinescu, Judith E Lupatsch, Florian Fitzal, Joerg Heil, Zoltán Mátrai, Jana de Boniface, Christian Kurzeder, Martin Haug, Alexandra Schulz. Pre- versus sub-pectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02 PREPEC): A pragmatic, multicenter, randomized, superiority trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-23-03.

Introduction: We developed tailored axillary surgery (TAS) to selectively remove positive nodes and omit axillary lymph node dissection (ALND) in patients with clinically node-positive breast cancer irrespective of the use of neoadjuvant chemotherapy. In this study, we evaluate the performance of this novel surgical concept that tailors the extent of axillary surgery to the extent of axillary disease. Methods: A prospective study was pre-specified to assess the performance of TAS in the international multicenter phase-III TAXIS trial randomizing patients with clinically node-positive breast cancer to undergo ALND or axillary radiation after TAS. TAS consists of selective removal of all palpably suspicious findings and the SLNs followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. Only patients with confirmed nodal disease at the time of surgery can be randomized in TAXIS; the first 200 randomized patients were analyzed together with the ones achieving nodal pCR in this study. ClinicalTrials.gov Identifier: NCT03513614. Results: A total of 296 patients with a median age of 56.5 years (range: 25-88 years) were included at 28 breast centers from four European countries, 125 (42.3%) of whom underwent NACT and 75 (25.3%) of whom had nodal pCR. Subtype was hormone receptor (HR) positive (+) and human epidermal growth factor receptor 2 (HER2) negative (-) in 194 (65.5%), HR+/HER2+ in 40 (13.5%), HR-/HER2+ in 17 (5.7%) and HR-/HER2- in 39 (13.2%) patients. Breast-conserving surgery was performed in 178 patients (60%) and mastectomy in 117 (40%). Imaging-guided localization was attempted in 258 patients (87.2%) and was successful in 243 (82.1%). TAS removed a median of two (interquartile range [IQR] 0-3) palpably suspicious lesions and two (IQR 1-3) SLNs, thereby successfully removing the clip in 279 (94.3%) patients. There were no significant differences by use of imaging-guided localization (94.6% with vs 92.1% without, p=0.47) or type of clip (p=0.19), but a trend toward lower rate of clip removal after NACT (91.2% with vs 96.5% without NACT, p=0.075). Palpable disease was left behind after TAS in two (2.1%) patients and no SLN was detected in three (3.1%). In the 200 randomized patients with confirmed nodal disease at the time of surgery, lymph node metastases were palpable at the time of initial diagnosis in 102 (51%) patients and detectable only by imaging in 98 (49%). The median number of lymph nodes removed by TAS was four (IQR 2-8), two (IQR 1-4) of which were positive. Completion ALND following TAS removed additional positive nodes in 71 of 100 (71%) patients in the control group (20% with one additional node, 9% with 2, 8% with 3, 6% with 4, and 28% with >4). The median number of additional lymph nodes removed by ALND was 14 (IQR 10-18), two (IQR 0-6) of which were positive. Of the 200 randomized patients, one in the TAS group received a radiotherapy boost and one in the ALND group returned to the operating room for residual suspicious findings on imaging. Discussion: The present results suggest that TAS has the potential to become the new axillary surgery standard in patients with clinically node-positive breast cancer. TAS was successfully performed in the vast majority of patients, with no further improvement by imaging-guided localization, which makes the procedure feasible at most breast centers. TAS selectively removed positive lymph nodes and was much less radical than ALND, but ALND removed additional positive nodes in more than two thirds of patients. Disease-free survival and quality of life will be assessed in the randomized trial. Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery to omit axillary lymph node dissection independently from the use of neoadjuvant chemotherapy in patients with clinically node-positive breast cancer: Pre-specified subproject within TAXIS (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD4-04.

Background Main weaknesses of neoadjuvant chemotherapy (NACT) to avoid axillary dissection (ALND) in patients with clinically node-positive breast cancer are frequent failure of achieving nodal pathologic complete response (pCR) and administration of chemotherapy even though not indicated otherwise in many cases. Tailored axillary surgery (TAS) was designed to selectively remove positive nodes and omit ALND in patients with clinically node-positive breast cancer either in the upfront surgery setting or in case of residual nodal disease after neoadjuvant therapy, which distinguishes this trial from all others ongoing and published. Trial design In this international, multi-center, phase-III, non-inferiority randomized controlled trial, including 61 study sites from six countries, we plan to randomize 1500 patients to either receive TAS followed by ALND and regional nodal irradiation excluding the dissected axilla, or receive TAS only followed by regional nodal irradiation including the full axilla. TAS consists of selective removal of the sentinel lymph nodes (SLNs) and all palpably suspicious findings, thereby tailoring the extent of axillary surgery to the extent of axillary disease, followed by specimen radiography to document removal of the clip placed in the sampled node. Imaging-guided localization is encouraged to increase the chances of clip removal. All patients undergo adjuvant whole-breast irradiation after breast conserving surgery and chest wall irradiation after mastectomy. Inclusion of internal mammary nodes is recommended irrespective of treatment arm. ClinicalTrials.gov Identifier: NCT03513614. Inclusion criteria - Clinically node-positive breast cancer (all molecular subtypes allowed) - Node-positivity palpable or detectable only by imaging at time of initial diagnosis - Newly diagnosed or isolated in-breast recurrence or second ipsilateral breast cancer after previous breast conserving surgery and sentinel procedure and at least 3 years disease free and no prior axillary dissection or axillary RT. - In case of prior neoadjuvant treatment: residual disease (including residual ITCs) confirmed by pathology at the time of surgery - Clipping of sampled axillary lymph node Exclusion criteria - Absence of clip in the specimen radiography - Palpable disease left behind in the axilla after TAS - No SLN identified in the axilla Specific aims To test the hypothesis that treatment with TAS and axillary radiotherapy is non-inferior to ALND in terms of disease-free survival (DFS) of clinically node-positive breast cancer patients. Secondary objective is to test if quality of life is significantly better with TAS and axillary radiotherapy compared to ALND. Statistical methods With type I error 5% and power 80%, 385 events will be needed to show non-inferiority of TAS and axillary RT in comparison to ALND with a non-inferiority hazard ratio (HR) of 1.289 (corresponding to a DFS at 5 years of 80% in the ALND arm and 75% in the TAS and axillary RT arm), including one interim analysis for efficacy/futility after 20% of the required events have occurred. The sample size needed is 1500 patients (750 per arm). The HR and one-sided 95% confidence interval will be calculated using a Cox regression model based on the per-protocol set. Present accrual and target accrual The trial was activated on 31 July 2018 and the first patient was randomized on 07 August 2018. As of 03 July 2020, 291 patients have been randomized. Accrual is currently running according to protocol and is planned until end of 2023 with the primary endpoint analysis expected in 2029. Contact information Prof. Dr. Walter Paul Weber, University Hospital Basel; Tel: +41 61 328 61 49; Walter.Weber@usb.ch Citation Format: Walter Paul Weber, Guido Henke, Stefanie Hayoz, Karin Ribi, Stefanie Seiler, Charlotte Maddox, Thomas Ruhstaller, Daniel Rudolf Zwahlen, Simone Muenst, Markus Ackerknecht, Florian Fitzal, Mihály Újhelyi, Christian Kurzeder, Loïc Lelièvre, Christoph Tausch, Daniel Egle, Jörg Heil, Zoltan Matrai, Michael Knauer. Tailored axillary surgery with or without axillary lymph node dissection followed by radiotherapy in patients with clinically node-positive breast cancer (SAKK 23/16 / IBCSG 57-18 / ABCSG-53 / GBG 101 - TAXIS): A multicenter randomized phase III trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-04-03.

IntroductionThe immediate (I-BR) or delayed-immediate (DI-BR) implant-based breast reconstruction (BR) of the affected breast following nipple, areola, skin-sparing mastectomy (NSM, ASM, SSM) techniques requires almost in all cases symmetrization of the contralateral breast. The long term results of implant-based BR (subpectoral or prepectoral) and symmetrization following advanced postmastectomy BR techniques significantly decrease over time and later result in a limited patient satisfaction rate. Beyond the satisfactory early results BRs, there are only limited long term data on cosmetics and patient satisfaction. In fact with time patient dissatisfaction necessitates repeated surgeries, with an extra load for both to the patient and the health system. The aim of the study is to gain high quality data about the deteriorating cosmetic outcomes of bilateral BRs on the long term. Trial design In this response-adaptive prospective randomized study patients are sub-grouped into 6 study groups after BR surgery with silicone implant (following uni- or bilateral NSM, ASM, SSM) with symmetrization in case of unilateral mastectomy (mastopexy and/or silicone implant and/or mesh sling technique to suspend the breast with or without reduction) or simple mastectomy without symmetrization. The planned number of patients is a minimum of 528 cases. The measurements of the breast, the ptosis, photo documentation using valid BCCT.core software, BREAST-Q questionnaire and Likert scale are performed preoperatively, 4 weeks after delayed BR with symmetrization, 3 months after, every 6 months for 5 years. Primary endpoint Using correlation analysis to measure objective changes over time in the quality of life (QoL) and patient satisfaction associated with the symmetry achieved by different surgical techniques up to five years of follow-up. To compare the QoL and the satisfaction rate in the control group with a simple mastectomy, bilateral SSM, ASM, NSM and BR. Secondary endpoint To determine the prognostic factors, patient subgroups, and surgical techniques associated with patients, surgery, and oncological therapies in an optimal way. Furthermore, the study should give relevant data about the oncoplastic concept of prophylactic SSM, ASM, or NSM on the contralateral side and BR, without the presence of hereditary breast and ovarian cancer syndrome, using the same surgical technique than on the affected side. The long term PRO results of postmastectomy BR should be necessarily part of the initial patient information in the future. Inclusion criteria- Under the age of 65 with uni- or bilateral primary breast cancer, needing advanced mastectomy independently of the axillary surgery, having I-BR os DI-BR on the ipsilateral side and symmetrization on the contralateral side - Control group: patients under 65 years with unilateral simplex mastectomy without BR. Exclusion criteria-Pregnancy-associated breast cancer-Prior breast surgery and/or radiotherapy -Severe non-surgical complication-Long-term steroid usage Present accrual and target accrual The trial was activated on 22 April 2020. As of 5 July, 23 patients have been randomized. Accrual is currently running according to protocol and is planned until 2025. Interim analysis performed after 2 years’ median follow-up period. The final analysis is performed 5 years after closing the patient inclusion period. Citation Format: Mihály Újhelyi, Ákos Sávolt, Orsolya Huszár, Orsolya Ping, Norbert Mészáros, Nóra Jani, Mátyás Újlaki, István Kenessey, Zsófia József, Zoltán Mátrai. Examining and comparing the temporal changes and results of cosmetic, quality of life and patient satisfaction achieved with immediate and delayed-immediate implant-based breast reconstruction procedures and contralateral symmetrisation techniques after skin-sparing mastectomies with unilateral simple mastectomy and with bilateral skin-sparing mastectomies and immediate implant-based breast reconstructive surgeries. (ClinicalTrials.gov Identifier: NCT04356235) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-23-01.

Introduction: Immediate breast reconstruction provides oncological safety, requires longer operation time. It does not influence the initiation of adjuvant therapy and radiological control, and results in favourable cosmetic outcome. Aim: Assessing the Hungarian data of immediate postmastectomy breast reconstructions, and comparing them to international findings. Method: Between May, 2011 and September, 2014 121 therapeutic and prophylactic, postmastectomy immediate breast reconstructions were performed in 100 patients. The clinico-pathological findings were assessed retrospectively, and surgical, oncological and cosmetic outcomes were evaluated statistically. Results: The mean age of patients was 42.6 years, the follow up time was 29.4 months, and the duration of operation was 132 minutes. Skin-sparing mastectomy was performed most commonly (64%) with submuscular tissue expander placement (70%). Early postoperative complication was identified in 18 patients, and loco-regional recurrence in 1 patient. Most patients (89%) were satisfied with the cosmetic outcome. The average initiation time of adjuvant therapy was 4.8 weeks. Conclusions: Immediate breast reconstruction is a safe and effective option in line with international findings. Orv. Hetil., 2016, 157(46), 1830–1838.

Introduction: The European Society of Breast Cancer Specialists has created quality indicators for breast units to establish minimum standards and to ensure specialist multimodality care with the conscious aim of improving outcomes and decreasing breast cancer mortality. Aim: The aim of this study was to analyse the breast cancer care in the National Institute of Oncology according to the European Society of Breast Cancer Specialists requirements and in a large number of cases in order to present representative clinico-pathological data on the incidence of breast cancer in Hungary. Method: According to the European Society of Breast Cancer Specialists uniformed criteria clinico-pathological data of multimodality treated breast cancer cases were retrospectively analysed between June 1, 2011 and May 31, 2012. Results: During the period of interest 906 patients underwent breast surgery for malignant or benign lesions. According to the European Society of Breast Cancer Specialists quality indicators the breast cancer care of the National Institute of Oncology is eligible. Conclusions: The diagnostic modalities and multimodality care of breast cancer of the National Institute of Oncology breast unit meets the critical mass and minimum standards of the European Society of Breast Cancer Specialists criteria. Orv. Hetil., 2016, 157(42), 1674–1682.

Absztrakt Az emlőrák sebészi terápiáját napjainkban és a jövőben is az egyre precízebb diagnosztikus módszerek és az egyre hatásosabb onkológiai kezelési eljárások határozzák meg. Az emlőmegtartás és az onkoplasztikai elvek alkalmazása egyre szélesebb körű; az axilla sebészi kezelésében az őrszemnyirokcsomó-biopszia az elsődleges, az axillaris blokkdissectio (ABD) indikációja tovább szűkült, és a sugárkezelés bizonyos esetekben az ABD alternatívája lett. Közleményünkben a III. Emlőrák-konszenzuskonferencia tartalmára épülve, a legfrissebb nemzetközi tanulmányok és szakértői javaslatokat figyelembe véve foglaljuk össze az emlőrák sebészi kezelésével kapcsolatos ajánlásainkat.

Background We examined time trends in axilla management among patients with early breast cancer in European clinical settings. Material and methods EUROCANPlatform partners, including population-based and cancer center-specific registries, provided routinely available clinical cancer registry data for a comparative study of axillary management trends among patients with first non-metastatic breast cancer who were not selected for neoadjuvant therapy during the last decade. We used an additional short questionnaire to compare clinical care patterns in 2014. Results Patients treated in cancer centers were younger than population-based registry populations. Tumor size and lymph node status distributions varied little between settings or over time. In 2003, sentinel lymph node biopsy (SLNB) use varied between 26% and 81% for pT1 tumors, and between 2% and 68% for pT2 tumors. By 2010, SLNB use increased to 79–96% and 49–92% for pT1 and pT2 tumors, respectively. Axillary lymph node dissection (ALND) use for pT1 tumors decreased from between 75% and 27% in 2003 to 47% and 12% in 2010, and from between 90% and 55% to 79% and 19% for pT2 tumors, respectively. In 2014, important differences in axillary management existed for patients with micrometastases only, and for patients fulfilling the ACOSOG Z0011 criteria for omitting ALND. Conclusion This study demonstrates persisting differences in important aspects of axillary management throughout the recent decade. The results highlight the need for international comparative patterns of care studies in oncology, which may help to identify areas where further studies and consensus building may be necessary.