Luisenkrankenhaus

Zielsetzung Gradgenaue Hilotherapy® verhindert, prophylaktisch eingesetzt Chemotherapie-induzierte-Polyneuropathien (CIPN); reaktiv - sekundär vermeidet es das Fortschreiten der CIPN und lindert bestehende Symptome.

In the ACOSOG Z0011 trial, patients with primary breast cancer (BC) and 1-2 tumor-involved sentinel lymph nodes (SLN) undergoing breast-conserving surgery gained no benefit from completing axillary lymph node dissection (cALND). This paper reports cALND rates performed in clinical routine on patients who would meet the Z0011 criteria. Further, patients still received cALND were analyzed concerning the number of non-sentinel metastases (NSM) to estimate occult axillary tumor burden. Data were retrospectively analyzed from patients treated in 179 German breast centers between 2008 and 2015. Time-trend rates were determined for cALND regarding the presence of axillary macrometastases or micrometastases. Descriptive statistics were used to report the number of NSM depending on the number of SLN removed, tumor-involved SLN, tumor stage (pT1-2), and immunohistochemical subtype. Factors associated with NSM were identified using multivariable logistic regression. Altogether, data for 188,909 patients were available, of whom 13,741 (7.3%) were identified eligible for the Z0011 criteria. For these patients, the cALND rate for macrometastases declined from 96.4% in 2008 to 49.7% in 2015, for micrometastases from 86.7 to 5.9%. In total 9773 patients still received cALND, 33.4% of whom had NSM. The NSM rates were: 38.8% for pN(1/1sn), 28.6% for pN(1/2sn), and 50.9% for pN(2/2sn). Hormone receptor (HR) positive/HER2+ showed the highest NSM rate (41.6%), HR-/HER2- the lowest rate (29.4%). The rate of cALND for ACOSOG Z0011 eligible patients has decreased substantially in routine care in our nationwide cohort. Our data reveal a relatively high prevalence of additional axillary NSM tumor burden.

In breast cancer, completion axillary lymph node dissection (cALND) was previously recommended for patients with at least one tumour-affected sentinel lymph node (SLN). Several prospective trials predominantly in patients undergoing breast-conserving surgery showed no benefit and increased arm morbidity with this procedure. We report the influence of these trials on clinical practice of patients undergoing mastectomy. We analysed prospectively collected data from patients with primary invasive breast cancer treated at German breast cancer units between January 2008 and December 2015. Time trends of cALND rates were analysed in patients undergoing mastectomy for T1/2N0M0 breast cancer with one or two tumour-involved SLNs. Multivariable logistic regression was used to determine factors influencing the decision not to perform cALND. Among the entire study cohort of 166,074 patients treated at 179 breast cancer units, 4093 patients (2%) had T1/2N0M0 breast cancer with one or two tumour-involved SLNs and underwent mastectomy. cALND rates decreased from 89.9% in 2010 to 55.5% in 2015 (p < 0.001). Rates decreased from 82% to 8% in patients with micrometastatic SLN disease and from 93% to 63% in those with macrometastasis (p < 0.001). In multivariable analysis, factors associated with omission of cALND were treatment at a general, nonacademic hospital, pT1 status, older age, higher number of removed SLNs, fewer tumour-affected SLNs, and SLN micrometastasis (all p < 0.001). Despite limited evidence from prospective trials relating to the omission of cALND specifically in patients undergoing mastectomy, our nationwide data show that use of cALND decreased in these patients in routine clinical practice.

Brustkrebspatientinnen wurde ehemals die komplettierende axilläre Lymphonodektomie (cALND) empfohlen, wenn mindestens ein Sentinel-Lymphknoten (SLN) tumorgefallen war. Verschiedene prospektive Studien, die hauptsächlich bei Patientinnen mit brusterhaltender Therapie durchgeführt wurden, zeigten keinen onkologischen Vorteil der cALND, jedoch eine erhöhte Morbidität dieses Eingriffs. Das Ziel unserer Untersuchung war es, den Einfluss dieser Studienergebnisse auf die Versorgungsrealität der Patientinnen mit Mastektomie zu untersuchen.

Abstract Background: Sentinel lymph node biopsy (SLNB) by radioactively labelled 99mTechnetium +/- patent blue is so far the current standard in SLN detection. However, it remains a time- and cost-consuming procedure requiring the availability of a nuclear medicine department and a precise coordination with the subsequent surgery. It could be desirable to empower surgeons to be independent from availability of a nuclear source and to spare patients from radioactivity. Indocyanine green (ICG) as a fluorescent coloring agent is already known as safe in diagnostics for heart, circulation, liver and eye disease and may represent a valid alternative to 99mTc and patent blue (PBD), especially as it does not cause aesthetic impairment of the breast, with ICG being only visible with near infra-red light. Methods: This prospective, randomized study is a non-inferiority trial to evaluate ICG-fluorescence as an alternative to either 99mTc and/or patent blue dye for sentinel lymph node detection of primary breast cancer with and without neoadjuvant chemotherapy. Patients, aged 18 - 80 years, with unilateral or bilateral, unifocal or multifocal/ multicentric primary breast cancer without signs of metastases and written consent are eligible for this study. ECOG status of 0-2 and life expectancy &amp;gt; 1 year is required. All BMI classes are admitted to the study, with predefined subgroups of a) &amp;lt;= 20 b) &amp;gt;20-30 c) &amp;gt;30-40 d) &amp;gt;40. Tumor stages included are a) Tis (&amp;gt;= 4 cm) b) T1 c) T2 and d) T3. ICG-guided SLNB may be applied in patients in the following settings: a) before neoadjuvant, b) after neoadjuvant chemotherapy. Primary Endpoints: Rate of SLN detection by either of the methods in the following 3 arms of the trial: Arm A: 99mTc + patent blue dye (PBD) Arm B: 99mTc + indocyanine green (ICG) Arm C: Indocyanine green (ICG) Secondary Endpoints: - Time to identify (TTI) sentinel lymph node(s) (min) - Number of sentinel lymph nodes (SLN) and non-sentinel lymph nodes (non-SLN) - Rate of concordance of detection by 99mTc+patent blue dye (PBD) vs. 99mTc + ICG - Dose of radioactivity omitted in Arm C vs. Arm A &amp; B Results: This trial is in progress. Citation Format: Kern P, Kimmig R, Rezai M, Hoffmann O, Bücker I, Braun M. Sentinel lymphnode biopsy (SLNB) and targeted axillary surgery (TAS) by indocyaningreen (ICG) and a novel near-infrared color camera system - a prospectively randomised, multicenter study to avoid radioactivity in a time-/cost-saving procedure in primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-05.

3062 Background: Adding an anti-PD-L1 checkpoint inhibitor durvalumab to standard chemotherapy (CT) may increase pathological complete response (pCR) in patients (pts) with TNBC. Methods: GeparNuevo randomizes pts to durvalumab (D) 1.5 g i.v. or placebo (pl) every 4 weeks (wks). D/pl monotherapy (0.75 g i.v.) is given for the first 2 wks (window phase), followed by a biopsy and D/pl plus nab-paclitaxel (nP) 125 mg/m² weekly for 12 wks, followed by D/pl plus epirubicin/cyclophosphamide (EC) q2 wks for 4 cycles. Randomization is stratified by stromal TILs (sTILs) (low (≤10%), intermediate (11-59%), high (≥60%)). Pts with primary cT1b-cT4a-d disease, centrally confirmed TNBC, and sTILs status can be included. Primary objective compares pCR (ypT0 ypN0) rates. Secondary objectives are pCR rates in stratified subpopulations and according to other pCR definitions; response rates; breast conservation rate; toxicity; compliance and survival. Change in sTILs, Ki67 and other immune biomarkers before CT, after the window phase and after CT will be correlated with outcome. The first 10, 20 and 30 pts will be included in safety interim analyses (SIA). Sample size was planned assuming a pCR rate of 48% for pl (nP treated TNBC cohort in GeparSepto) and of 66% for D (as clinically meaningful benefit), requiring 158 pts to show superiority of D (2-sided α = 0.2, 80% power). Assuming a 10% drop-out rate 174 pts will be randomized. Results: Since 6/2016, 50 pts were recruited within 16 sites; data are presented as available until 01/2017. Median age is 49 years; 86% NST and G3 tumors; sTILs categories 40% low, 40% intermediate and 20% high. Blinded SIA was performed. No pt interrupted D/pl, one nP and one EC. Treatment delay was observed in 9 pts (20.0%) in D/pl, 18 (41.9%) in nP and 2 (13.3%) in EC; dose was reduced in 10 pts (23.3%) in nP and in 4 (26.7%) in EC. 10 pts (20%) had at least one grade 3-4 AE: 4 haematological and 6 non-haematological AEs. 4 SAEs and 5 immune related AEs were reported. 2 pts discontinued study treatment prematurely in the EC phase. Conclusions: The addition of D to standard nP-EC is feasible and does not result in an increased toxicity. Clinical trial information: NCT02685059.

508 Background: Neratinib (N) is an irreversible pan-HER tyrosine kinase inhibitor with clinical efficacy in trastuzumab (T) pre-treated HER2-positive (HER2+) metastatic breast cancer. In HER2+ ear...

Large scale genotyping studies have identified more than 70 single nucleotide polymorphisms (SNPs) that are associated with breast cancer (BC) risk. The knowledge about risk factors that are associated with prognosis is however growing much slower. Aim of this study was therefore to investigate nine known breast cancer risk SNPs for their prognostic relevance.