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Purpose Although the incidence of distant relapse is decreasing, 20–30% of patients with early breast cancer die of metastasis. The aim of this study is to characterize patients with metastasis-free survival(MFS) less than 5 years, to analyze the most probable site of metastases according to the internally and externally validated BRENDA-score. The BRENDA-score is a combination of the biological subtype and clinical staging. Method 3832 patients with primary diagnosis of breast cancer and either distant metastatic recurrence within 5 years or MFS ≥ 5 years were assigned to this study. Patients were classified for metastatic recurrence according to the BRENDA-score. 1765 patients were in a validation set. Statistical methods were Kaplan–Meier curves, Cox regression analysis, Exhausted CHAID, likelihood-ratio tests and the Nearest Neighbor Estimation method. Results There was a significant(p Conclusion The evaluation showed that the BRENDA-Score is a robust predictive tool for breast cancer recurrence and site of metastases in the first five years after diagnosis. It outperforms intrinsic subtypes and the Nottingham prognostic score. The BRENDA-score could be a tool for a risk orientated and targeted follow up.

As the available information about breast cancer is growing every day, the decision-making process for the therapy is getting more complex. ChatGPT as a transformer-based language model possesses the ability to write scientific articles and pass medical exams. But is it able to support the multidisciplinary tumor board (MDT) in the planning of the therapy of patients with breast cancer? We performed a pilot study on 10 consecutive cases of breast cancer patients discussed in MDT at our department in January 2023. Included were patients with a primary diagnosis of early breast cancer. The recommendation of MDT was compared with the recommendation of the ChatGPT for particular patients and the clinical score of the agreement was calculated. Results showed that ChatGPT provided mostly general answers regarding chemotherapy, breast surgery, radiation therapy, chemotherapy, and antibody therapy. It was able to identify risk factors for hereditary breast cancer and point out the elderly patient indicated for chemotherapy to evaluate the cost/benefit effect. ChatGPT wrongly identified the patient with Her2 1+ and 2+ (FISH negative) as in need of therapy with trastuzumab and called endocrine therapy “hormonal treatment”. Support of artificial intelligence by finding individualized and personalized therapy for our patients is unavoidable in this time of rapidly expanding amount of information. ChatGPT has the potential to find its spot in clinical medicine, but the current version is not able to provide specific recommendations for the therapy of patients with primary breast cancer.

CD8+ cytotoxic T-lymphocytes, NKp46+ natural killer cells and F4/80+ macrophages in tumors of AOM/DSS and APCMin mice. Analysis of cytokines secreted by small intestinal organoids upon MS-444 treatment.

MS-444 restores splenic lymphoid follicles and decreases spleen weight in APCMin mice.

HuR is an RNA-binding protein implicated in immune homeostasis and various cancers, including colorectal cancer. HuR binding to AU-rich elements within the 3′ untranslated region of mRNAs encoding oncogenes, growth factors, and various cytokines leads message stability and translation. In this study, we evaluated HuR as a small-molecule target for preventing colorectal cancer in high-risk groups such as those with familial adenomatosis polyposis (FAP) or inflammatory bowel disease (IBD). In human specimens, levels of cytoplasmic HuR were increased in colonic epithelial cells from patients with IBD, IBD-cancer, FAP-adenoma, and colorectal cancer, but not in patients with IBD-dysplasia. Intraperitoneal injection of the HuR small-molecule inhibitor MS-444 in AOM/DSS mice, a model of IBD and inflammatory colon cancer, augmented DSS-induced weight loss and increased tumor multiplicity, size, and invasiveness. MS-444 treatment also abrogated tumor cell apoptosis and depleted tumor-associated eosinophils, accompanied by a decrease in IL18 and eotaxin-1. In contrast, HuR inhibition in APCMin mice, a model of FAP and colon cancer, diminished the number of small intestinal tumors generated. In this setting, fecal microbiota, evaluated by 16S rRNA gene amplicon sequencing, shifted to a state of reduced bacterial diversity, with an increased representation of Prevotella, Akkermansia, and Lachnospiraceae. Taken together, our results indicate that HuR activation is an early event in FAP-adenoma but is not present in IBD-dysplasia. Furthermore, our results offer a preclinical proof of concept for HuR inhibition as an effective means of FAP chemoprevention, with caution advised in the setting of IBD. Cancer Res; 77(9); 2424–38. ©2017 AACR.

Alpha diversity in feces of AOM/DSS and APCMin upon MS-444 treatment and indicator OTUs in AOM/DSS mouse feces.

Weight curves of AOM/DSS and APCMin mice, DSS water consummtion and large bowel tumorigenesis in APCMin mice

HuR nucleocytoplasmic shuttling is increased with increasing MS-444 concentrationsin an acute colitis model.

CRISPR/Cas9 HuR ko in RAW 264.7 macrophage cells confirmed by Sanger sequencing and Western blot analysis.

Crypt-villus length and HuR subcellular distribution as analyzed by immunohistochemistry and Western blot of nuclear and cytoplasmic fractions from isolated tumors in MS-444 treated and control mice.

Additional information on mouse experiments, colonoscopy, histology, immunohistochemical analysis and amplicon sequencing for microbiota analysis

Phylum and family levels of APCMin and AOM/DSS mouse feces upon MS-444 treatment.

Antibody list, organoid culture medium reagents and primer sequences

Purpose Perioperative cognitive dysfunction can be observed in all age groups of patients. Sometimes, this is more stressful to the patient than the actual surgical wound. Enhanced recovery after surgery pathways screen for patients at risk and lead to early post-surgical intervention. To prevent cognitive dysfunction, a prehabilitation approach might be useful. Methods This systematic literature review provides an overview on the current knowledge on prehabilitation for cognitive dysfunction for gynaecological patients by searching the National Library of Medicine (PubMed) in February 2020 to identify publications regarding presurgical cognitive training with three different search terms. Results 501 articles were identified and after screening for eligibility five were left for further analysis. Generally, cognitive function is split into several cognitive aspects like anxiety or memory, speed, attention, flexibility or problem-solving functions. Each of these aspects can/need to be trained to show an improvement after general anaesthesia. Training possibilities range from relaxation methods via music, one-on-one personal training sessions to electronically supported training units. Conclusion Prehabilitation of the cognitive function can be split in different cognitive domains. Each of these domains seem to be influenced by training. The training itself can be based on applications or known relaxation methods or even old-fashioned board games. The evidence is, however, still low and there is a need for further studies.

Objective To determine the area most at risk of delayed cerebral ischemia (DCI) in relation to the location of the ruptured aneurysm in patients with aneurysmal subarachnoid hemorrhage (aSAH) and, therefore, help to choose the site for focal multimodal neuromonitoring. Methods We retrospectively analyzed angiographic findings, CCT scans, and patient charts of patients who were admitted with aSAH to our neurosurgical intensive care unit between 2009 and 2017. DCI was defined as infarction on CCT 2–6 weeks after aSAH. Results DCI occurred in 17.9% out of 357 included patients. A DCI occurring in the vascular territory of the artery carrying the ruptured aneurysm was found in 81.0% of patients with anterior circulation aneurysms but only in 16.7% with posterior circulation aneurysms (Fisher’s exact, p=0.003). The vascular territory most frequently showing a DCI was the ipsilateral MCA territory (86.7%) in ICA aneurysms, the contra- (71.4%) and the ipsilateral (64.3%) ACA territory in ACA aneurysms, the right (93.8%) and the left (81.3%) ACA territory in AcomA aneurysms, and the ipsilateral MCA territory in MCA aneurysms (69.2%) as well as in VA/PICA/SCA aneurysms (100.0%). DCI after the rupture of a BA aneurysm occurred with 33.3% in 6 out of 8 vascular territories, respectively. DCI of multiple vascular territories occurred in 100.0% of BA aneurysms, 87.5% of AcomA aneurysms, 71.4% of ACA aneurysms, 40.0% of ICA aneurysms, 38.5% of MCA aneurysms, and 33.3% of VA/PICA/SCA aneurysms. Discussion Few studies exist that could determine the area most at risk of a DCI after an aSAH. Our data could identify the territory most at risk for DCI with a probability of > 60% except for BA aneurysms, which showed DCI in various areas and patients suffering from multiple DCIs. Either the ipsilateral ACA or MCA were affected by the DCI in about 80% of ACA and more than 90% of AcomA, ICA, MCA, and VA/PICA/SCA aneurysms. Therefore, local intraparenchymal neuromonitoring in the ACA/MCA watershed area might detect the vast majority of DCIs for all aneurysm locations, except for BA aneurysms. In ACA and AcomA aneurysms, bilateral DCI of the ACA territory was common, and bilateral probe positioning might be considered for monitoring high-risk patients. Non-focal monitoring methods might be preferably used after BA aneurysm rupture.

ZusammenfassungIm Zuge der zunehmenden Arbeitsverdichtung sowie Schichtdienstarbeit sind Beschäftigte im Medizinsektor häufig einem Interrollenkonflikt ausgesetzt. Gerade die Vereinbarkeit von Beruf und Familie ist ein wichtiger Faktor für nachhaltige Mitarbeiterzufriedenheit, Leistungsfähigkeit und Gesundheit. Im Rahmen des Qualitätsmanagements erfolgte im Sommer 2017 eine anonyme und freiwillige Befragung aller Beschäftigten der Universitätsfrauenklinik Ulm. Dabei wurde ein standardisierter Fragebogen zur Arbeitszufriedenheit sowie Vereinbarkeit von Familie und Beruf ausgegeben, indem u.a die Work-Family-Conflict (WFC) und Family-Work-Conflict (FWC) Scale verwendet wurde. Die Rücklaufquote betrug 63% (n=136). Als „Medizinisches Personal“ (n=115) wurde der Zusammenschluss aus Arzt/Ärztin (n=33), Pflege (n=53) und Hebammen (n=31) definiert. Zwischen Beschäftigten mit (n=73) und ohne Kind (n=59) fand sich kein signifikanter Unterscheid im WFC sowie FWC. Die Gruppe der Pflegekräfte/Hebammen sowie Ärzte hatte einen signifikant höheren Interrollenkonflikt (p

Introduction Tubal ligation is the most common contraceptive method worldwide. Apart from a very low pearl index and anxiety relief, other benefits are not commonly recognised. In young patients, there is the post-operative risk of regretting the decision with the need for In-Vitro-Fertilisation or refertilising surgery. Positive side effects have not been widely published. In our study we investigated the change in the female sexual function index score after tubal ligation. Material and method In this survey the FSFI score of participants around the time of the tubal ligation was compared with the FSFI score of intermediate and long-term time distance to the ligation. Results The data indicate an increase in younger women seeking information on permanent contraception and whilst the FSFI score of the early group indicates a risk of female sexual dysfunction, the intermediate and long-term FSFI scores are comparable to published control groups. Discussion Besides the obvious benefit of a low pearl index, tubal ligation may contribute to reduce the risk of female sexual dysfunction in the mid and long term. Informed consent is essential for the surgeon and patient to weigh up the risks and benefits individually including possible future perspectives on family planning., publishedVersion

Large translational research projects may contribute to further progress in cancer treatment by exploring molecular biology, immunologic approaches and identification of new prognostic and predictive factors. Therefore, the BRandOBio-project combines a clinical registry for collection of patient and tumor characteristics with a biobank comprising tumor and liquid biopsies. In addition, sociodemographic, environmental and lifestyle factors of included patients with primary newly diagnosed breast or ovarian cancer, other rare malignant ovarian tumors or gestational trophoblastic disease are prospectively collected. The target population includes the German “Alb-Allgau-Bodensee Region” which constitutes the outreach area of the University Hospital Ulm with affiliated academic centers and private practices. Clinical data combined with primary tumor tissue samples and longitudinal repeatedly collected blood samples [before, 6 (in high-risk situations), 12, 36 and 60 months after treatment and at relapse] will be acquired from more than 4000 patients within the next years. Standardized questionnaires are given to patients of the University Hospital Ulm and eight selected external sites for assessing life style and cancer risk factors. Concomitantly, storage of paraffin-embedded tumor samples as well as liquid biopsy samples will allow translational research projects, for example in terms of investigating circulating DNA and germ line DNA from cell pellets. Starting in January 2016 at the University Hospital Ulm, 19 additional external sites started recruiting patients in March 2017. As of September 15th 2019, 2151 patients with newly diagnosed cancers could be recruited (2044 breast cancer; 107 ovarian cancer). Nearly all patients provided biological samples (tumor and liquid biopsy) and about 80% returned the standardized questionnaire. After 1 year follow-up, blood samples were available from more than 80% of the participating patients. The BRandO BIO study is a large prospective cohort study with integrated comprehensive biobank and evaluation of sociodemographic and life style factors of gynecological cancer patients in a well-defined geographical area in the South West of Germany. Continuous high patient recruitment and stable rates over 80% for returned questionnaires as well as for repeated blood sampling show high acceptance of the BRandO study program and confirms feasibility of the project.

Objective: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. Methods: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. Results: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. Conclusion: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.

ZusammenfassungDie plastisch-kosmetische Brustrekonstruktion wird aus unterschiedlichsten Indikationen durchgeführt. Patientinnen mit einem entsprechenden Eingriff sind körper-bewusst und nehmen an verschiedensten körperlichen Aktivitäten bzw. Sport teil. Da die postoperativen Empfehlungen nur auf niedrigem Evidenzniveau bei Brustrekonstruktion existieren, wurde mittels einer online Befragung ein erster Überblick über die Empfehlungen erhoben. Demzufolge kann die Wiederaufnahme von Sport unterstützt werden, es sollte jedoch auf mögliche Risiken hingewiesen werden. Grundsätzlich ist nach derzeitigem Kenntnisstand nicht von Sport und körperlicher Aktivität nach einem Brustwiederaufbau abzuraten.

Background Guideline recommendations for axillary surgical approach in breast cancer (BC) treatment changed over the last decade. Methods Data from all invasive BC patients (n = 5344) treated with breast conserving surgery (BCS) at the breast cancer centers of the University Hospital Ulm (U‑BCC) and the community hospital Dachau (D‑BCC) were included into a retrospective analysis for assessing information on axillary surgery between 2003 and 2016 based on the documented cancer registry data. Results The average annual rate of sentinel node biopsy (SNB) was 85.5 % and 87.2 % in Ulm and Dachau, respectively. SNB was performed more precisely at the U‑BCC with a median of 2.4 resected lymph nodes (LN) compared to a median of 3.2 resected LN in Dachau. Median number of resected LN for axillary lymph node dissection (ALNE) showed a statistically significant reduction over time in Ulm (rs = − 0.82; p Conclusion Changes in axillary surgery over time can be seen in the annual statistics of the reviewed BCCs. With BCS, mostly SNB was performed and numbers of removed LN in ALNE have decreased. In the U‑BCC, the rate of 2° ALNE dropped after the publication of the Z0011 data. The fact that no such decrease for 2° ALNE was found in D‑BCC suggests that university hospitals implement new data and research results into clinical routine earlier than peripheral community hospitals.

Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project [1]. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell’s c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p &lt, 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3), intermediate risk: HR = 5.0, 95%CI.(3.6–6.9), high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p &lt, 0.001, NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.

Background: The implantation of a subcutaneous implantable venous access device in patients with a gynecological cancer disease could be necessary because of different causes, e.g. application of chemotherapy or parenteral nutrition in case of advanced cancer. 4 years after implementation of the Seldinger-technique in the subclavian vein as standard way of port-catheter-implantation at department of gynecology at the University-Hospital in Ulm a retrospective analysis of complication-rates was performed to define internal standards for this procedure. Methods: Between 01/2014 and 07/2018 we reviewed all patients who received a port implantation at the gynecological department. The standard way of port-implantation used in this cohort was Seldinger-technique. All Data assessed were used anonymously. Patients-characteristics, tumor-entity, surgical and anesthesiological management, morbidity and port catheter associated complications (thrombosis, infections etc.) were analyzed. Results: A total of 638 were included. The implantation was performed in Seldinger-technique. Port catheter implantation was successfully performed in 96.6%. The implantation on the left subclavian vein significantly showed a higher rate of success than in the right subclavian vein (98.2% vs. 95.3%, p=0,036). Significant higher rates of associated thromboses was found in patients with a port implantation on the left side (5.9% vs. 2.0%; p=0.036). Obesity (BMI ≥ 30 kg/ m2) leads to a significant higher rate of venous misplacements (p=0.027). Compared to local anesthesia and analgosedation, general anesthesia leads to a significant lower rate of perioperative complications (20.3% vs. 22.4% vs. 13.1%; p=0.014). Perioperative application of antibiotics seems to reduce postoperative infection rates, even if the results are not significant. Conclusion: Seldinger-Technique is an efficient way for port-implantation. Especially patients with a high potential of complications, like obesity with BMI >30kg/m², or other risk factors, the left subclavian vein should be preferred, as well as general anesthesia. Perioperative application of antibiotics (e.g. single-shot antibiotics) should be considered. Trial registration: retrospectively registered

Background: It is still unclear whether oncological patients harbor a higher risk for an infection with the SARS-CoV-2 and for developing severe forms of COVID-19. Furthermore, it is unclear whether an infection affects essential therapy treatment and if a therapy increases the risk for an infection. Method(s): We tested every patient (n=1286) in 7 different oncology outpatient clinics from 04/15/2020 and 04/26/2020 for COVID-19 infection regardless of whether symptoms were present or not. Virus RNA was extracted using the MGIEasy extraction kit in combination with SP-960 robots and a RT qPCR was performed. Result(s): From 1286 tested patients 40 (3.1%) patients were identified positive. Only two of those (5.0%) had mild symptoms whereas one positive patient (2,5%) was treated stationary with pneumonia. The majority (37/40) was asymptomatic virus-carriers (92,5 %). Noteworthy is the fact that 22 (55%) of the positively tested patients were undergoing systemic therapy of which 10 (45.5%) patients received chemotherapy and 4 (18.2%) patients received immunomodulating antibodies. Conclusion(s): A consequent testing for COVID-19 in cancer patients is obligate to identify asymptomatric positive carrier to separate this potential vector group from COVID negative patients since the majority (37/40) of positive patients was asymptomatic virus-carriers (92,5 %). The data we collected contrasts strongly the hypothesis that cancer patients are suspected to be highly vulnerable for SARS-CoV-2 infections. Only a minority (3/40) of positively tested tumor patients showed symptoms. An asymptomatic COVID-19 infection seems to have no impact on the further course of a chemotherapy. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2020

Reconciliation of family and work life is an important topic for employees. Due to common work in shifts within the health care sector, this is even more essential for health care workers and has great implications in work satisfaction and individuals ́ health. Within all employees of the department of OB/GYN of the German university hospital Ulm, an anonymous and voluntary survey on compatibility of work and family was performed in the summer of 2017. The questionnaires consisted of established and newly designed tools to assess reconciliation of family/work life as well as work-family (WFC) and family-work conflict (FWC). Return rate of questionnaires was 63% (n=136). Physicians (n=33), nurses (n=53), and midwives (n=31) were grouped together as "medical staff" (n=115). There was no significant difference between employees with (n=73) or without children (n=59) regarding WFC and FWC. The group of nurses/midwives and the group of physicians had a significantly higher inter-role conflict (p0.001) than the group of administrative staff. A negative correlation with "work satisfaction" was found for WFC and FWC. The group of nurses/midwives has significantly higher inter-role conflicts than the administrative staff. Especially the negative correlation of work satisfaction and inter-role conflicts shows the enormous need for improvement in sufficient compatibility of work and family life of employees in the health care sector. This needs to be addressed quickly and effectively as there is an alarming deficit of nurses and midwives in the German health care system.Im Zuge der zunehmenden Arbeitsverdichtung sowie Schichtdienstarbeit sind Beschäftigte im Medizinsektor häufig einem Interrollenkonflikt ausgesetzt. Gerade die Vereinbarkeit von Beruf und Familie ist ein wichtiger Faktor für nachhaltige Mitarbeiterzufriedenheit, Leistungsfähigkeit und Gesundheit. Im Rahmen des Qualitätsmanagements erfolgte im Sommer 2017 eine anonyme und freiwillige Befragung aller Beschäftigten der Universitätsfrauenklinik Ulm. Dabei wurde ein standardisierter Fragebogen zur Arbeitszufriedenheit sowie Vereinbarkeit von Familie und Beruf ausgegeben, indem u.a die Work-Family-Conflict (WFC) und Family-Work-Conflict (FWC) Scale verwendet wurde. Die Rücklaufquote betrug 63% (n=136). Als „Medizinisches Personal“ (n=115) wurde der Zusammenschluss aus Arzt/Ärztin (n=33), Pflege (n=53) und Hebammen (n=31) definiert. Zwischen Beschäftigten mit (n=73) und ohne Kind (n=59) fand sich kein signifikanter Unterscheid im WFC sowie FWC. Die Gruppe der Pflegekräfte/Hebammen sowie Ärzte hatte einen signifikant höheren Interrollenkonflikt (p0,001) als die Gruppe Verwaltung/Sonstige. Es zeigte sich sowohl für den WFC als auch den FWC ein signifikanter negativer Zusammenhang mit dem Faktor Arbeitszufriedenheit. Vor allem die Gruppe Pflege/Hebammen weist hinsichtlich des Interrollenkonflikts eine signifikant höhere Belastung als die Gruppe der Verwaltung auf. Der negative Zusammenhang von WFC/FWC mit dem Faktor Arbeitszufriedenheit deutet auf einen hohen Handlungsbedarf hin. Gerade vor dem Hintergrund des Pflege- und Hebammenmangels in Kliniken muss dies effektiv und zeitnah geschehen.

Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. Our retrospective study shows our experience with NGS of 324 genes in combination with protein expression in patients with advanced breast cancer (aBC). The primary purpose was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Between April 2018 and September 2019, 41 patients with aBC were offered a NGS test. The test was used to detect clinically relevant genomic alterations and to support further targeted therapy decisions. Hormone receptors, ERBB2 of tumors and PD-L1 was stained by immunohistochemistry. The data was recorded up to September 2019. After prior consent 41 results were available for further analysis. The most common BC subtypes were triple-negative (n = 16), HR+/ERBB2− (n = 15), and ERBB2+ (n = 9), with one missing data of the primary tumor. 27 patients had more than one genetic alteration. The most common alterations were PIK3CA (n = 14) and ERBB2 alterations (n = 11). Followed by ESR1 (n = 10), FGFR1 (n = 7) and PTEN (n = 7). 68% of the alterations were clinically relevant (tier I and II of ESCAT classification). The most common treatment recommendation was ERBB2-directed therapy (single or double blockade, trastuzumab emtansine and lapatinib) followed by alpelisib in combination with fulvestrant. Comprehensive genomic profiling combined with protein expression analysis in aBC allowed a guided personalized therapy for half of our patients. So far there are no well-defined tools allowing interpretations of genomic alterations detected by NGS in combination with protein expression and other factors.