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

Az axilla optimális kezelése pozitív őrszemnyirokcsomó esetén korai invazív emlőrákban. Az OTOASOR vizsgálat előzetes eredményei

Introduction: Sentinel lymph node biopsy alone has become an acceptable alternative to elective axillary lymph node dissection in patients with clinically node-negative early-stage breast cancer. Approximately 70 percent of the patients undergoing breast surgery develop side effects caused by the axillary lymph node dissection (axillary pain, shoulder stiffness, lymphedema and paresthesias). Aim: The current standard treatment is to perform completion axillary lymph node dissection in patients with positive sentinel lymph node biopsy. However, randomized clinical trials of axillary dissection versus axillary irradiation failed to show survival differences between the two types of axillary treatment. 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 axillary lymph node dissection to axillary nodal irradiation in patients with sentinel lymph node-positive primary invasive breast cancer. Method: Patients with primary invasive breast cancer (clinically lymph node negative and less than or equal to 3 cm in size) were randomized before surgery for completion axillary lymph node dissection (arm A-standard treatment) or axillary nodal irradiation (arm B-investigational treatment). Sentinel lymph node biopsy was performed by the radio-guided method. The use of blue-dye was optional. Sentinel lymph nodes were investigated with serial sectioning at 0.5 mm levels by haematoxylin and eosin staining. In the investigational treatment arm patients received 50Gy axillary nodal irradiation instead of completion axillary lymph node dissection. Adjuvant treatment was recommended and patients were followed up according to the actual institutional guidelines. Results: Between August 2002 and June 2009, 2106 patients were randomized for completion axillary lymph node dissection (1054 patients) or axillary nodal irradiation (1052 patients). The two arms were well balanced according to the majority of main prognostic factors. Sentinel lymph node was identified in 2073 patients (98.4%) and was positive in 526 patients (25.4%). Fifty-two sentinel lymph node-positive patients were excluded from the study (protocol violation, patient's preference). Out of the remaining 474 patients, 244 underwent completion axillary lymph node dissection and 230 received axillary nodal irradiation according to randomization. The mean length of follow-up to the first event and the mean total length of follow-up were 41.9 and 43.3 months, respectively, and there were no significant differences between the two arms. There was no significant difference in axillary recurrence between the two arms (0.82% in arm A and 1.3% in arm B). There was also no significant difference in terms of overall survival between the arms at the early stage follow-up. Conclusions: The authors conclude that after a mean follow-up of more than 40 months axillary nodal irradiation may control the disease in the axilla as effectively as completion axillary lymph node dissection and there was also no difference in terms of overall survival. Orv. Hetil., 154(49), 1934-1942