Az örökletes emlőrák szűrésének, megelőzésének és kezelésének új nemzetközi irányvonalai – hazai vonatkozásokkal

Absztrakt Bevezetés: Az örökletes emlőrák szűrése, megelőzése és kezelése összetett, multidiszciplináris feladat. A familiáris emlőrák ellátására új ajánlásokat publikáltak az Egyesült Királyságban. Célkitűzés: A szerzők az angliai és skóciai ajánlásokat, azok evidenciáit és az ezzel kapcsolatos magyarországi helyzetet foglalják össze. Módszer: A National Institute for Health and Care Excellence és a Familial Breast Cancer Report (NHS Scotland) ajánlásai és a hazai gyakorlat elemzése. Eredmények: Az új ajánlások jelentősen növelik a genetikai tesztek és az ezzel kapcsolatos genetikai tanácsadások számát. Az új ajánlások alapján lényegesen több mágneses rezonanciás vizsgálat javasolt az emlőszűrésben. Az érintett egyéneknek közepes kockázattól felfelé kemoprevenció ajánlható. Az örökletes emlőrák szisztémás kezelésében új utakat nyithatnak az egyes platinaszármazékokkal és a poli-ADP-ribóz polimeráz inhibitorokkal végzett klinikai vizsgálatok. Az egészségügyi költségvetést számottevően megterhelhetik a jelentősen megnövekedett genetikai tesztvizsgálatok, a genetikai tanácsadások, az emlő mágneses rezonanciás vizsgálatai. Következtetések: A fenti ajánlások bizonyos területeken meg fogják változtatni a familiáris emlőrák ellátásának jelenlegi klinikai gyakorlatát. Orv. Hetil., 2016, 157(28), 1117–1125

Sentinel lymph node biopsy following previous axillary surgery in recurrent breast cancer.

Ipsilateral breast recurrence or second primary breast cancer can develop in patients who have undergone breast conserving surgery (BCS) and axillary surgery. The purpose of this study was to examine the feasibility of a reoperative sentinel lymph node biopsy (SLNB) as a repeated axillary staging procedure.From August 2014 through January 2017 patients with locally recurrent breast cancer or with BRCA mutation requiring risk reduction mastectomy as a second surgical procedure, underwent repeat SLNB in three Hungarian Breast Units with a radiocolloid (and blue dye) technique.Hundred and sixty repeat SLNBs were analysed, 80 after previous SLNB and 80 after previous total or partial axillary lymph node dissection (ALND). SLN identification was successful in 106 patients (66%); 77/80 (77.5%) and 44/80 (55%) in the SLNB and ALND groups, respectively. (p < 0.003). Extra-axillary lymph drainage was more frequent in the ALND group (19/44, 43,2% versus 7/62, 11,3%; p < 0.001). Lymphatic drainage to the contralateral axilla was observed in 14 patients (11 in the ALND group, p = 0.025), isolated parasternal drainage was detected in 4 patients (p = 0.31). Only 9/106 patients with successful repeat SLNB (8,8%, all with 1 SLN removed) had SLN metastases CONCLUSIONS: Repeat SLNB is feasible in patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous BCS and axillary staging. Repeat SLNB should replace routine ALND as the standard axillary restaging procedure in recurrent disease with a clinically negative axilla. Preoperative lymphoscintigraphy is important to explore extra-axillary lymphatic drainage in this restaging setting

In situ ductails emlőcarcinoma kombinált sebészi- és sugárkezelése: Multicentrikus prospektív randomizált vizsgálat = Combined surgical and radiotherapy treatment of ductal carcinoma in situ of the breast: Multicentric prospective randomized study

289 duktális in situ emlőrák (DCIS) miatt emlőmegtartó műtéttel kezelt beteget randomizáltunk a lokális recidíva szempontjából meghatározott rizikó csoportok szerinti besorolás után. Immunhisztokémiai (IHK) módszerrel vizsgáltuk a lehetséges molekuláris prognosztikai markerek (ER, PR, Her2, p53, Bcl2 és Ki-67) expresszióját. A pozitív IHK reakció a Her2 (38%), p53 (36%) és Ki-67 (47%) markereknél a nukleáris grade-del korrelált. Ezzel szemben az ER (77%), PR (67%) és Bcl2 (67%) pozitivitás szignifikáns inverz összefüggésben volt a grade-del. A klinikai eredményeket 3 éves medián követési idő után 278 betegnél elemeztük. A magas rizikójú betegcsoportban emlőmegtartó műtét és sugárkezelés után 4 (1,7%) lokális recidíva és 1 (0,4%) távoli áttét alakult ki, emlődaganatos haláleset nem volt. A helyi daganatkiújulás 3 és 5 éves valószínűsége 1,1% és 3,1% volt. Tapasztalataink alapján a DCIS egyértelmű diagnózisa esetén az őrszem nyirokcsomó biopszia rutinszerű elvégzése nem indokolt. Korai eredményeink alapján az emlő DCIS kezelésében az emlőmegtartó műtét és posztoperatív sugárkezelés alkalmazásával a helyi daganatkiújulás éves aránya 1% alatt marad. A tumorágy "boost" kezelés hatékonyságának megítélésére és a vizsgált molekuláris markerek prognosztikai/prediktív értékének elemzésére hosszabb követési idő után lesz lehetőségünk. A molekuláris prognosztikai faktorok IHK vizsgálata segítségünkre lehet a DCIS biológiai heterogenitásának feltérképezésében. | 289 patients with ductal carcinoma in situ (DCIS) treated by breast-conserving surgery were randomised according to predetermined risk groups. Immunohistochemistry (IHC) was performed to detect the expression of potential molecular prognostic markers (ER, PR, Her2, p53, Bcl2, and Ki-67). The positive immunostaining for Her2 (38%), p53 (36%), and Ki-67 (47%) correlated with a high nuclear grade. Significant inverse correlation was found between the expression of ER (77%), PR (67%), Bcl2 (67%) and grade. Clinical results was analysed for 278 patients at a median follow-up of 36 months. In the high-risk patient group 4 (1.7%) local recurrences and 1 (0.4%) distant metastasis occurred. No patient died of breast cancer. The 3- and 5-year probability of local recurrence was 1.1% and 3.1%, respectively. Based on our experience, the definitive diagnosis of DCIS does not warrant sentinel lymph node biopsy. Preliminary results suggest that breast-conserving surgery followed by radiotherapy yields an annual local recurrence rate of less than 1% in patients with DCIS. Further follow-up is needed to define the clinical benefit of tumour bed boost irradiation and to analyse the prognostic/predictive value of molecular prognostic factors. IHC of molecular prognostic markers can assist to gain insight into the biologic heterogeneity of DCIS

Predictive Potential of RNA Polymerase B (II) Subunit 1 (RPB1) Cytoplasmic Aggregation for Neoadjuvant Chemotherapy Failure

We aimed to investigate the contribution of co-translational protein aggregation to the chemotherapy resistance of tumor cells. Increased co-translational protein aggregation reflects altered translation regulation that may have the potential to buffer transcription under genotoxic stress. As an indicator for such an event, we followed the cytoplasmic aggregation of RPB1, the aggregation-prone largest subunit of RNA polymerase II, in biopsy samples taken from patients with invasive carcinoma of no special type. RPB1 frequently aggregates co-translationally in the absence of proper HSP90 chaperone function or in ribosome mutant cells as revealed formerly in yeast. We found that cytoplasmic foci of RPB1 occur in larger sizes in tumors that showed no regression after therapy. Based on these results, we propose that monitoring the cytoplasmic aggregation of RPB1 may be suitable for determining—from biopsy samples taken before treatment—the effectiveness of neoadjuvant chemotherapy

Apocrine Encapsulated Papillary Carcinoma of the Breast: The First Reported Case with an Infiltrative Component

Apocrine encapsulated papillary carcinoma (EPC) of the breast is a rare neoplasm, and only 10 cases have been reported in the literature to date. Although EPC by definition lacks a peripheral myoepithelial layer, all previously published apocrine EPC cases were clinically indolent and lacked a conventional invasive component. Herein, we report the 11th case of apocrine EPC, which had a conventional invasive carcinoma component and provides evidence of the malignant potential of this entity. We postulate that apocrine EPC is most likely a morphological variant of conventional EPC, with the same unpredictable malignant potential as non-apocrine cases

The relationship of multifocality and tumor burden with various tumor characteristics and survival in early breast cancer

The presence of multifocality and the aggregate tumor size were retrospectively analysed in adatabase of 1071 operated breast cancers. Around aquarter of all these cancers involved multiple foci, while atenth of the total demonstrated more than one invasive focus. Although the multifocal cancers were smaller and more often screen-detected than the unifocal cancers, their aggregate tumor size was larger, and they more frequently displayed casting-type calcifications in the mammogram and HER2 positivity. Lobular histology favoured larger tumor burden. The invasive multifocal cancers were more commonly lymph node-positive than the other tumors. In asubgroup of 584 patients with amedian follow-up time of 5 years, the larger size of the invasive tumor, the presence of LVI or lymph node involvement, HER2 positivity and triple negativity were associated with apoorer RFS and OS, while the outcome of screen-detected tumors was superior to that of non-screen-detected or interval cancers. Alarge tumor size, lymph node positivity and HER2 positive or triple negative phenotypes were independent determinants of apoorer survival rate. Keywords: breast cancer, multifocality, prognostic factor, tumor burden

Emlőcentrum - virtuális klinika az emlőbetegek multidiszciplináris ellátására

Breast cancer, the most prevalent female malignancy represents a major health problem. Breast cancer mortality may be halved by high quality mammography screening and care. The most efficient screening and the best treatment of patients are available at the breast centers that are equipped with special facilities, expertise and significant experience via the treatment of a high number of patients. Breast center is a virtual unit based on the collaboration of various professionals; a tight institutional frame is not a must. In these comprehensive centers, 150 breast cancer patients per year at a minimum are treated, and the most efficient special treatment methods are available. The core members of the staff are the breast pathologists, the mammographists, the breast surgeons, the oncologists/oncoradiologists, the breast nurses, the technicians and the data managers. An easy access to the service of the non-core members, the plastic surgeons, the psychologists, the psychiatrists and the clinical geneticists is necessary. An optimal collaboration of the various experts may be achieved by a training of the members, regular multidisciplinary meetings and guidelines developed and accepted by all. The requirements of a breast center have been published by the European Society of Mastology (EUSOMA), and a directory of the accredited European breast centers is maintained. The Breast Unit of the University of Szeged has been found eligible by EUSOMA to be included in the directory of the European breast units. Two mammographists do screening-mammography and clinical examination, 2 pathologists perform cytopathological, histopathological and immunohistochemical examinations. Three surgeons operate on more than 250 breast cancer patients per year, and apply wire or isotope (ROLL) localisation in case of non-palpable lesion. A plastic surgeon is available if necessary. In a half of all cases, sentinel mapping is performed with isotope- and blue dye-labelling. Two radiotherapists apply conformal radiotherapy in 250 cases per year, and 2 oncologists perform modern chemotherapies in 200 cases as a yearly average; 50 new advanced/metastatic cases per year require oncological treatments. Breast nurses, a psycho-oncologist and a mental hygienist nurse assist the team. There is access to lymphedema treatment and physiotherapy. The final goal of the program is to provide all women with high quality mammography screening and care, if necessary