Search

Die malignen Speicheldrusentumoren sind eine extrem heterogene Gruppe seltener Tumoren mit groser klinischer, pathologischer und molekularbiologischer Variabilitat. Die chirurgische Resektion stellt in den meisten Fallen die Therapie der Wahl dar. Bei lokal fortgeschrittenen oder aggressiven malignen Tumoren ist haufig eine adjuvante Radiotherapie indiziert, die das Risiko fur ein Lokalrezidiv reduziert. Kontrovers diskutiert wird das Ausmas der Parotidektomie bei Karzinomen der Glandula parotis, insbesondere die Behandlung des N. facialis. Einigkeit herrscht weitestgehend daruber, diesen Nerv, wann immer moglich, zu erhalten, sofern nicht eine praoperative Parese oder eine offensichtliche intraoperative Tumorinfiltration einem Nervenerhalt entgegenstehen. Resezierte Anteile des N. facialis sollten moglichst sofort rekonstruiert werden. Die Chirurgie der von den kleinen Speicheldrusen ausgehenden Karzinome entspricht weitgehend dem Vorgehen bei Kopf-Hals-Plattenepithelkarzinomen. Bei adenoidzystischen Karzinomen ist aufgrund des perineuralen Wachstums und des haufigen Bezugs zur Schadelbasis eine R0-Resektion oft nicht zu erreichen, was die besondere Bedeutung der adjuvanten Radiotherapie bei dieser Entitat unterstreicht. Die Indikation der elektiven „neck dissection“ im cN0-Fall wird ebenfalls uneinheitlich gestellt. Wahrend einige Autoren die generelle Lymphknotenausraumung bei allen Karzinomen fordern, lautet der uberwiegende Konsens, eine elektive „neck dissection“ bei fortgeschrittener Tumorgrose, High-grade-Karzinomen und erhohtem Sicherheitsbedurfnis durchzufuhren. Die zunehmende Erkenntnis genomischer Alterationen und tumorspezifischer Signalwege eroffnet neue vielversprechende Moglichkeiten zielgerichteter molekularer Therapien im fortgeschrittenen Tumorstadium.

The aim of this study was to analyze and compare the accuracy and quality of six 3D printing systems available on the market. Data acquisition was performed with 12 scans of human mandibles using an industrial 3D scanner and saved in STL format. These STL files were printed using six different printing systems. Previously defined distances were measured with a sliding caliper on the 72 printed mandibles. The printed models were then scanned once again. Measurements of volumes and surfaces for the STL files and the printed models were compared. Accuracy and quality were evaluated using industrial software. An analysis of the punctual aberration between the template and the printed model, based on a heat map, was also carried out. Secondary factors, such as costs, production times and expendable materials, were also examined. All printing systems performed well in terms of accuracy and quality for clinical usage. The Formiga P110 and the Form 2 showed the best results for volume, with average aberrations of 0.13 ± 0.23 cm3 and 0.12 ± 0.17 cm3, respectively. Similar results were achieved for the heat map aberration, with values of 0.008 ± 0.11 mm (Formiga P110) and 0.004 ± 0.16 mm (Form 2). Both printers showed no significant difference from the optimal neutral line (Formiga P110, p = 0.15; Form 2, p = 0.60). The cheapest models were produced by the Ultimaker 2+, with an average of 5€ per model, making such desktop printers affordable for rapid prototyping. Meanwhile, advanced printing systems with sterilizable and biocompatible printing materials, such as the Formiga P110 and the Form 2, fulfill the high expectations for maxillofacial surgery.

Purpose Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.

Odontogene Zysten werden prinzipiell entweder mittels Zystektomie oder mittels Zystostomie oder auch mit einer Kombination beider Verfahren behandelt. Bei der Zystostomie erfolgt eine partielle Offnung der Zyste mit dem Ziel der Dekompression und Drainage, um das Zystenwachstum zu stoppen und im langerfristigen Verlauf durch Offenhalten des Zugangs das Lumen der Zyste zu verkleinern. Bei der Zystektomie wird der Zystenbalg in einer Operation vollstandig entfernt und der chirurgische Zugang dicht verschlossen. Der grose Vorteil der Zystektomie besteht in der kurzen Behandlungszeit und der Moglichkeit der vollstandigen histologischen Aufarbeitung des Zystenbalgs, um den Typ der Zyste und deren Charakteristika zu bestimmen. Die resultierende Knochenhohle nach Zystektomie kann entweder nur mit Blut, autologem Knochen oder verschiedenen Knochenersatzmaterialen gefullt werden. Die Literaturdaten belegen, dass es bei intakten Knochenwanden, sicherem und dichtem Wundverschluss ohne die Verwendung zusatzlicher Fullungsmaterialien regelmasig zur vollstandigen knochernen Regeneration auch bei grosen Zysten kommt. Bei zystisch knochernen Kieferdefekten mit Verlust mehrerer Knochenwanden oder dem randstandigen Periost wird allerdings die Verwendung autologer Beckenkammspongiosa zur besseren knochernen Regeneration empfohlen. Aufgrund ihres lokal aggressiven Wachstums und ihrer Rezidivgefahr nimmt die odontogene Keratozyste eine Sonderstellung ein. Randomisierte und kontrollierte Studien, die die Uberlegenheit einer bestimmten Zusatztherapie (Nachfrasen, Carnoy-Losung, flussiger Stickstoff) gegenuber einer anderen Therapie in der Behandlung von odontogenen Keratozysten zeigen, fehlen bisher.

ZusammenfassungNachdem in den letzten Jahren bei der Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom zunehmend Substanzen mit einer guten Effektivität zum Einsatz kommen, die spezifische Signalwege angreifen, sind nun neue Therapien und Ansätze hinzugekommen, die sich tatsächlich auf ganz spezifische Veränderungen beziehen wie die Behandlung von Patientinnen mit HR+/HER2−-Tumoren mit einer PIK3CA-Mutation. Ebenso ist die Behandlung von Patientinnen mit einer BRCA1- oder BRCA2-Mutation durch die Einführung der PARP-Inhibitoren verbessert worden. Nun wird zunehmend versucht, Therapieindikationen aufgrund molekularer Muster auszudehnen und weitere Patientinnen zu identifizieren, die von einer Therapie profitieren könnten, und die neu etablierten Therapiemethoden in bestehende Therapiesequenzen einzubinden. Diese Übersichtsarbeit fasst die neuesten Erkenntnisse in diesem Zusammenhang zusammen.

Beim fruhen Mammakarzinom wurde beobachtet, dass ereignisfreies und Gesamtuberleben bei Patientinnen mit gutem Therapieansprechen auf eine primare systemische Chemotherapie (PST) besser sind als bei Patientinnen mit Residualtumoren in der Brust oder in der Axilla nach der PST. Somit ermoglicht die PST sowohl die Verkleinerung des Tumors als auch eine In-vivo-Sensitivitatstestung der Chemotherapie. Denn wenn sich eine pathologische Komplettremission (pCR) herausstellt, kann sie als Surrogatparameter fur verbessertes ereignisfreies Uberleben und Gesamtuberleben dienen. Das gilt insbesondere fur Tumoren mit aggressiver Tumorbiologie wie tripelnegatives Mammakarzinom (TNBC, „triple-negative breast cancer“) und HER2-positives Mammakarzinom, und fuhrte zur Entwicklung der postneoadjuvanten Therapiekonzepte. Einige wichtige aktuelle Studienergebnisse werden in der vorliegenden Arbeit dargestellt. Vor dem Hintergrund der beschriebenen Daten sollte bei Patientinnen mit TNBC oder mit HER2-positiver Erkrankung die Chemotherapie bevorzugt im neoadjuvanten Setting verabreicht werden, um dann ggf. durch anschliesende Gabe einer postneoadjuvanten Chemotherapie die Prognose der Patientin verbessern zu konnen. Im Fall einer Non-pCR nach neoadjuvanter Chemotherapie sollte eine postneoadjuvante Chemotherapie mit der Patientin diskutiert werden. Die Frage, ob die adjuvante Strahlentherapie parallel oder sequenziell durchgefuhrt werden soll, ist abhangig von der jeweiligen Substanz und bedarf weiterer Untersuchungen.

This paper deals with the estimation of the lateral motion of steel strips during the hot strip rolling process in a tandem finishing mill. The method presented in this paper uses an image sequence captured by a 2D-CMOS camera. In the considered application, just a small segment of the strip is inside the camera field of view and thus an image sequence has to be used for online estimation. An optimization-based algorithm uses the image data and the knowledge about the constraints of the strip movement in the rolling gap for robust estimation of the lateral position and width of the strip. Measurement data from a tandem finishing mill show the performance of the designed algorithm.

Substances with good effectiveness that intervene in specific signalling pathways have been used increasingly in recent years in the treatment of patients with advanced breast cancer, and new therapies and approaches have now been added, which actually relate to quite specific changes, such as the treatment of patients with HR+/HER2 tumours with a PIK3CA mutation. The treatment of patients with a BRCA1 or BRCA2 mutation has also been improved by the introduction of PARP inhibitors. Attempts are now being made increasingly to extend treatment indications based on molecular patterns, to identify other patients who could benefit from a treatment and to integrate the newly established treatment methods in existing therapy sequences. This review articles summarises the latest information in this connection.

Background In EMBRACA, talazoparib prolonged progression-free survival versus chemotherapy (hazard ratio [HR] 0.542 [95% confidence interval (CI) 0.413-0.711]; P Patients and methods This randomized phase III trial enrolled patients with gBRCA1/2-mutated HER2-negative ABC. Patients received talazoparib or physician's choice of chemotherapy. OS was analyzed using stratified HR and log-rank test and prespecified rank-preserving structural failure time model to account for subsequent treatments. Results A total of 431 patients were entered in a randomized study (287 talazoparib/144 chemotherapy) with 412 patients treated (286 talazoparib/126 chemotherapy). By 30 September 2019, 216 deaths (75.3%) occurred for talazoparib and 108 (75.0%) chemotherapy; median follow-up was 44.9 and 36.8 months, respectively. HR for OS with talazoparib versus chemotherapy was 0.848 (95% CI 0.670-1.073; P = 0.17); median (95% CI) 19.3 months (16.6-22.5 months) versus 19.5 months (17.4-22.4 months). Kaplan–Meier survival percentages (95% CI) for talazoparib versus chemotherapy: month 12, 71% (66% to 76%)/74% (66% to 81%); month 24, 42% (36% to 47%)/38% (30% to 47%); month 36, 27% (22% to 33%)/21% (14% to 29%). Most patients received subsequent treatments: for talazoparib and chemotherapy, 46.3%/41.7% received platinum and 4.5%/32.6% received a poly(ADP-ribose) polymerase (PARP) inhibitor, respectively. Adjusting for subsequent PARP and/or platinum use, HR for OS was 0.756 (95% bootstrap CI 0.503-1.029). Grade 3-4 adverse events occurred in 69.6% (talazoparib) and 64.3% (chemotherapy) patients, consistent with previous reports. Extended follow-up showed significant overall improvement and delay in time to definitive clinically meaningful deterioration in global health status/quality of life and breast symptoms favoring talazoparib versus chemotherapy (P Conclusions In gBRCA1/2-mutated HER2-negative ABC, talazoparib did not significantly improve OS over chemotherapy; subsequent treatments may have impacted analysis. Safety was consistent with previous observations. PRO continued to favor talazoparib.

The treatment of patients with early breast cancer has always been characterised by escalation by new therapies and de-escalation through identification of better treatment regimens or introduction of better tools to estimate prognosis. Efforts in some of these areas in the last few years have led to solid data. The results of the large studies of de-escalation through use of multi-gene tests are available, as are the results of some studies that investigated the new anti-HER2 substances T-DM1 and pertuzumab in the early treatment situation. Several large-scale studies examining the role of CDK4/6 inhibitors will soon be concluded so innovations can be anticipated in this area also. This review article will summarise and classify the results of the latest publications.

Purpose The treatment of advanced stages of medication-related osteonecrosis of the jaw (MRONJ) remains challenging. In order to improve decision making concerning the therapy, we examined the change of patients’ quality of life (QoL) after surgical treatment of MRONJ stage III. Method The primary outcome variable was patients’ QoL. It was preoperative (T0), 6 weeks postoperative (T1) and 6 months postoperative (T2) assessed by the European Organisation for Research and Treatment of Cancer QoL-H&N35 (EORTC QoL-H&N35) and the Oral Health Impact Factor-G14 (OHIP-G14) questionnaire in a prospective cohort study. Other variables included location, age, sex, risk factors, and recurrence. Descriptive statistics and general multivariate regression models were calculated. Results Forty-three patients with stage III MRONJ underwent surgery. OHIP-G14 scores decreased (improvement) statistically significant (p = .001) by 52.02% (T0-T1) and 56.45% (T1–T2). EORTC QoL-H&N35 showed statistical improvement for “swallowing” (p = .007), “opening mouth” (p = .045), “painkiller” (.005), “weight loss” (.004), “pain” (p = .001), “trouble with social eating” (p = .001), “trouble with social contact” (p = .001), and “teeth” (p = .001). Patients who developed a recurrence did not show any significant higher (worse) scores in OHIP G14 or EORTC QoL-H&N35 scores compared with patients without recurrence. Twenty-nine out of 36 patients showed full mucosal healing (T2). For patients with no full mucosal healing, a downgrade to stage I was achieved. Conclusion In terms of QoL patients with stage III MRONJ do benefit from surgical treatment. The incident of a recurrence seems to have no significant impact on patients QoL.

Across ages and levels of competition, sport coaches in the U.S. encounter athletes who are learning English (ALEs). ALEs bring significant linguistic and cultural resources, but can struggle to co...

ZusammenfassungVom 14. bis 16. November 2019 fand in Lissabon die fünfte internationale Konsensuskonferenz ABC5 (Advanced Breast Cancer Fifth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms statt. Ziel ist es, die Behandlung der Patientinnen mit fortgeschrittenem Mammakarzinom weltweit auf evidenzbasierter Grundlage zu standardisieren und sicherzustellen, dass Patientinnen überall auf der Welt adäquat behandelt werden und Zugang zu neuen Therapien erhalten. Ein inhaltlicher Schwerpunkt lag dieses Jahr auf neuen Entwicklungen und Studienergebnissen beim fortgeschrittenen Mammakarzinom sowie der Präzisionsmedizin. Zudem ist die Zusammenarbeit mit den Patientenvertreterinnen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz, weshalb in dem international zusammengesetzten ABC-Panel auch Patientenvertreterinnen sind. Im vorliegenden Manuskript werden die Abstimmungsergebnisse der ABC5-Panelisten vor Ort durch eine Arbeitsgruppe deutscher Brustkrebsexperten für den Therapiealltag in Deutschland kommentiert. Der Kommentierung liegen die Empfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Kommission „Mamma“, zugrunde. Sie erscheint sinnvoll, da in den ABC-Konsensus auch länderspezifische Besonderheiten einfließen.

The usage of locally produced pure rapeseed oil fuel (R100) according to fuel standard DIN 51605 in agricultural machinery can contribute to protecting the climate, water, and soil. Besides economic aspects, uncertainties concerning the long-term operation reliability and limited exhaust emissions of R100-operated agricultural machinery are hindering market entry. Thus, the aim of this research is to evaluate field experiences, such as downtimes and repairs, engine oil quality, and cold start behaviour, over a total period of more than 50,000 operation hours with 18 tractors. The tested tractors range from European Union exhaust gas stages I to IV and were configured for the use of R100. Additionally, performance, nitrogen oxides, and particulate matter were measured on a tractor test stand. The tractors demonstrated their full functionality under usual Bavarian farm conditions in daily use. Within the tractor fleet, no serious engine damage was observed, while minor malfunctions and necessary repairs occurred just occasionally. The operational reliability of the tested rapeseed-oil-fuelled tractors seemed to be comparable to that of diesel-fuelled tractors. The results of recurrent power and fuel consumption measurements gave no indication of engine deterioration. Furthermore, measurements proved that differences in exhaust gas emissions between R100 and diesel operation were marginal. Tractor models with exhaust gas after treatment systems were characterized by low emissions of nitrogen oxides and particulate matter in particular. With the 18 tractors running on R100, about 220 tonnes of CO2eq per year were saved on average from 2015 to 2017. It can be concluded that the usage of pure rapeseed oil fuel (R100) in compatible agricultural machinery is an implementable alternative to diesel fuel and can make an important contribution to reducing greenhouse gas emissions in agriculture. Nevertheless, there are some challenges to solve, particularly for modern agricultural machines with engines with exhaust gas aftertreatment systems.

The aim of the study was to evaluate the surgical outcome of patients with advanced medication-related osteonecrosis of the jaw (MRONJ) treated with different flaps for soft tissue closure. Only MRONJ stage III patients with a minimum follow-up of 6 months were included in our prospective study. The soft tissue closure techniques were: Mylohyoid Muscle Flap, Buccal Fat Flap and mucoperiosteal flap alone. Potential risk factors and surgical side effects were analyzed. Relapses occurred in 12 of 44 included cases and 38 reached mucosal integrity within the follow-up. Cases treated with the muscle or fat flap showed better results regarding the recurrence rate (p < 0.001) and soft tissue healing (p = 0.002): only 3 of 33 developed a relapse, and 31 of 33 reached mucosal integrity. The outcome was worse if MRONJ occurred at the front areas of the jaw (p = 0.025). Postoperative, the pain level was reduced significantly (p < 0.001). Partial hypoesthesia of the lip arose in 18 cases. An impairment of the long-term prosthetic rehabilitation has not been seen.Patients with MRONJ stage III undergoing surgery benefit from extensive soft tissue closure.

ZusammenfassungFür Patientinnen mit einem lokal fortgeschrittenen bzw. metastasierten Mammakarzinom wurden in den letzten Jahren neue und effektive Therapien wie CDK4/6-Inhibitoren, PARP-Inhibitoren und ein PD‑L1-Inhibitor eingeführt. In dieser Übersichtsarbeit wird ein Update zu den vorhandenen Studien mit ihrer Datenlage gegeben. Ebenso werden 2 innovative Anti-HER2-Therapien dargestellt (Trastuzumab-Deruxtecan und Tucatinib), für die die Ergebnisse aus neuen Studien berichtet worden sind. Molekulare Tests bieten die Möglichkeit, Patientinnenpopulationen zu definieren oder auch Therapieverläufe zu monitorieren. Dieses kann helfen, Patientinnen mit spezifischen Eigenschaften zu identifizieren, um diesen eine individuelle zielgerichtete Therapie im Rahmen von Studien zukommen zu lassen. In einer großen Studie konnte der Nutzen einer solchen Biomarker-Studie zum ersten Mal beschrieben werden.

PurposePalbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, approved in combination with endocrine therapy for the treatment of women and men with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer (HR+/HER2− ABC). In the phase 2, open-label, PALOMA-1 trial, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) versus letrozole alone (hazard ratio, 0.488; 95% CI 0.319‒0.748;P = 0.0004; median PFS, 20.2 vs 10.2 months, respectively) in postmenopausal women with estrogen receptor–positive (ER+)/HER2− ABC. Here, we present the final overall survival (OS) and updated safety results.MethodsPostmenopausal women with ER+/HER2− ABC were randomized 1:1 to receive either palbociclib (125 mg/day, 3/1 schedule) plus letrozole (2.5 mg/day, continuous) or letrozole alone (2.5 mg/day, continuous). The primary endpoint was investigator-assessed PFS; secondary endpoints included OS and safety.ResultsA total of 165 patients were randomized. At the data cutoff date of December 30, 2016 (median duration of follow-up, 64.7 months), the stratified hazard ratio for OS was 0.897 (95% CI 0.623–1.294;P = 0.281); median OS in the palbociclib plus letrozole and letrozole alone arms was 37.5 and 34.5 months, respectively. The median time from randomization to first subsequent chemotherapy use was longer with palbociclib plus letrozole than letrozole alone (26.7 and 17.7 months, respectively). The most frequently reported adverse event in the palbociclib plus letrozole arm was neutropenia (any grade, 75%; grade 3 or 4, 59%).ConclusionsPalbociclib plus letrozole treatment led to a numerical but not statistically significant improvement in median OS.Pfizer Inc (NCT00721409)

The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 – 16, 2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.

Problem definition: The growing trend in online shopping has sparked the development of increasingly more sophisticated product recommendation systems. We construct a model that recommends a personalized discounted product bundle to an online shopper that considers the trade-off between profit maximization and inventory management, while selecting products that are relevant to the consumer’s preferences. Academic/practical relevance: We provide analytical performance guarantees that illustrate the complexity of the underlying problem, which combines assortment optimization with pricing. We implement our algorithms in two separate case studies on actual data from a large U.S. e-tailer and a premier global airline. Methodology: We focus on simultaneously balancing personalization through individualized functions of consumer propensity-to-buy, inventory management for long-run profitability, and tractability for practical business implementation. We develop two classes of approximation algorithms, multiplicative and additive, to produce a real-time output for use in an online setting. Results: Our computational results demonstrate significant lifts in expected revenues over current industry pricing strategies on the order of 2%–7% depending on the setting. We find that on average our best algorithm obtains 92% of the expected revenue of a full-knowledge clairvoyant strategy across all inventory settings, and in the best cases this improves to 98%. Managerial implications: We compare the algorithms and find that the multiplicative approach is relatively easier to implement and on average empirically obtains expected revenues within 1%–6% of the additive methods when both are compared with a full-knowledge strategy. Furthermore, we find that the greatest expected gains in revenue come from high-end consumers with lower price sensitivities, and that predicted improvements in sales volume depend on product category and are a result of providing relevant recommendations.

Die individuellen Therapiemoglichkeiten der Patientin mit einem metastasierten Brustkrebs werden immer spezifischer. Fur Therapieentscheidungen in der metastasierten Situation liegt keine ausreichende Evidenz aus klinischen Studien fur alle Behandlungssituationen und Subgruppen vor. Dieses macht die Erhebung und systematische Auswertung von Real-World-Daten zur Erstellung von Real-World-Evidenz sinnvoll. Um bei der Behandlung von Patientinnen mit einem metastasierten Mammakarzinom eine stadien- und tumorspezifische Therapie identifizieren zu konnen, wurde das PRAEGNANT-Netzwerk (Prospective Academic Translational Research Network zur Optimierung der onkologischen Versorgungsqualitat im fortgeschrittenen therapeutischen Umfeld) etabliert. Ziel ist es, die medizinische Versorgung von Patientinnen mit metastasiertem Mammakarzinom in der realen Welt zu beleuchten, Wirkungen und Nebenwirkungen der Therapiekonzepte zu erfassen, die Veranderung der Lebensqualitat unter der Therapie mit zu verfolgen, Patientinnen zu identifizieren, die an einer klinischen Arzneimittelstudie teilnehmen konnen, und durch Untersuchung der molekularen Tumoreigenschaften des Mammakarzinoms Patientinnen eine zielgerichtete Therapie in klinischen Studien zu ermoglichen. Dieser Artikel fasst die bereits erhobenen Daten aus dem PRAEGNANT-Netzwerk zusammen und beleuchtet die Frage der Ubertragbarkeit der verschiedenen Endpunkte aus klinischen Studien in die reale Behandlungssituation.

ZusammenfassungIm Rahmen von derzeit laufenden Studien werden in naher Zukunft wichtige translationale Fragestellungen von klinischer Relevanz geklärt werden. Zum einen muss die Rolle der PD‑L1-Expression, nachdem sie für die Indikationsstellung für Atezolizumab in der 1. Therapielinie bei Patientinnen mit einem metastasierten triplenegativen Mammakarzinom (TNBC) von Relevanz ist, weiter geklärt werden. In einer neoadjuvanten Studie beim TNBC mit Pembrolizumab konnte kein Zusammenhang zwischen Wirksamkeit und PD‑L1-Expression gefunden werden. Sowohl mit als auch ohne Expression war die pCR höher, wenn Pembrolizumab zur Chemotherapie hinzugefügt wurde. Des Weiteren wird für die bei Keimbahnmutation von BRCA1/2 zugelassenen PARP-Inhibitoren nach weiteren Patientengruppen gesucht, in denen eine Wirksamkeit besteht. Dieses sind z. B. Patientinnen mit Mutationen in anderen Genen, die an der homologen Rekombination beteiligt sind, oder Patientinnen mit Tumoren, die bei globalen Tests zu homologen Rekombinationsdefizienzen (HRDTests) eine Auffälligkeit zeigen. Auch die Frage, ob und mit welchen Chemotherapie-Kombinationspartnern eine PARP-Inhibition zusammen gegeben werden kann, wird derzeit sowohl beim Mamma- als auch beim Ovarialkarzinom untersucht. Während sich die Daten zum verbesserten Gesamtüberleben bei den CDK4/6-Inhibitoren konsolidieren, wächst auch das Wissen um molekulare Veränderungen unter der Therapie und bei der Progression unter der Therapie. Sowohl die Anhäufung von PI3K-Mutationen als auch PTEN-Veränderungen könnten bei der Planung von Folgetherapien eine Rolle spielen. Diese Übersichtsarbeit fasst diese aktuellen Entwicklungen beim Mammakarzinom und teilweise auch beim Ovarialkarzinom zusammen.

Science, technology, engineering, and mathematics (STEM) fields are notably important for innovation and technological development, which in turn are seen as drivers of social and economic growth. Hence, researchers and policy-makers have paid substantial attention to analyzing and promoting high-growth ventures in STEM fields. However, STEM fields are highly gender-skewed, regardless of whether the population considered is students, faculty members, graduates, top managers, or entrepreneurs. This is noticeable in the small number of women entrepreneurs with STEM backgrounds. This underrepresentation of women in innovation-driven business startups highlights existing gender biases and systemic disadvantages in social structures, making visible the double masculinity that exists at the intersection of STEM and entrepreneurship. This article addresses this issue by combining insights from research about women’s entrepreneurship and research about the gender aspects of STEM fields. We emphasize institutional, organizational, and individual factors influencing women’s entrepreneurship in STEM fields, laying the foundation for the articles included in this special issue. Finally, we discuss the way forward for research on the gender aspects of STEM entrepreneurship to help us create the knowledge needed to close this gender gap.

Background: Talazoparib is a potent oral inhibitor of poly(ADP-ribose) polymerase (PARP) 1 and 2, which significantly improved progression-free survival versus standard-of-care chemotherapy in patients with HER2-negative advanced breast cancer (ABC; locally advanced/metastatic breast cancer) and a germline BRCA1/2 mutation (gBRCA1/2mut) in the Phase 3 EMBRACA trial (Litton J, et al. N Engl J Med. 2018;379:753-763). An integrated analysis of five clinical trials (Phase 1-3) in multiple tumor types was performed to evaluate the safety of talazoparib administered at 1 mg/day (d). Methods: Data were pooled from the ongoing Phase 3 randomized EMBRACA trial in HER2-negative gBRCA1/2mut ABC (NCT01945775), the Phase 2 non-randomized ABRAZO trial in gBRCA1/2mut ABC (NCT02034916), the Phase 1 trial in advanced/recurrent solid tumors (NCT01286987), the Phase 1 cardiac repolarization trial in advanced solid tumors (NCT03042910), and an ongoing open-label extension trial (NCT02921919). Results: 494 patients who received talazoparib 1 mg/d were included (Table). The most common all-grade adverse drug reactions (≥20%) with talazoparib were ANEMIA (includes preferred terms: anemia, decreased hemoglobin, decreased hematocrit; 49.6%), fatigue (47.6%), nausea (44.3%), NEUTROPENIA (neutropenia, decreased neutrophil count; 30.2%), THROMBOCYTOPENIA (thrombocytopenia, decreased platelet count; 29.6%), headache (26.5%), diarrhea (22.7%), alopecia (22.3%; Grade 1, 20.6%; Grade 2, 1.6%), vomiting (22.3%), and decreased appetite (20.2%). Grade 3/4 toxicities (≥10%) with talazoparib were ANEMIA (35.2%), NEUTROPENIA (17.4%), and THROMBOCYTOPENIA (16.8%). Overall 24 patients (4.9%) died within 30 days after the last dose of study drug; the most common cause of death was disease progression (13 patients; 2.6%). Other causes of death were reported in 1 patient each (cerebral hemorrhage, dyspnea, lung infection, lung metastases, respiratory failure, suspected veno-occlusive liver disease, and worsening of neurological symptoms); cause of death was not reported for 4 patients. The most common treatment-related serious adverse event was anemia (4.3%). Median duration of talazoparib exposure was 5.4 months (range, 0.0-61.1). Median relative dose intensity (defined as actual-dose intensity/planned-dose intensity) was 92.8%. Dosing interruptions due to TEAEs were reported for 48.6% of patients receiving talazoparib; median duration of dosing interruption due to TEAEs was 8.0 days (range, 1.0-121.0). Hematologic TEAEs (≥5%) associated with dose modification (interruption or reduction) included anemia (33.0%), neutropenia (15.8%), thrombocytopenia (13.4%), and decreased platelet count (5.9%); non-hematologic TEAEs (≥2%) associated with dose modification included fatigue (4.3%), vomiting (2.6%), and nausea (2.0%). Only 18 patients (3.6%) permanently discontinued due to a TEAE (anemia, 3 patients [0.6%]; other events, 1 patient each [0.2%]). Conclusions: Talazoparib monotherapy at 1 mg/d was generally well tolerated with few patients permanently discontinuing talazoparib due to AEs. Common toxicities were primarily hematologic and were manageable through dosing modifications and/or standard supportive care. Funding: Pfizer Inc. Table Summary of TEAEsPhase 3 EMBRACA trialOpen-label trialsTalazoparibTalazoparib mg/dTalazoparib 1 mg/d1 mg/d populationbTalazoparibPCTABRAZONCT01286987NCT03042910OLEaTotalN=286N=126N=83N=77N=37N=46N=494Any TEAE282 (98.6)123 (97.6)81 (97.6)75 (97.4)28 (75.7)39 (84.8)484 (98.0)Grade 3 or 4 TEAE193 (67.5)80 (63.5)54 (65.1)52 (67.5)9 (24.3)21 (45.7)326 (66.0)Treatment-related Grade 3 or 4 TEAE159 (55.6)61 (48.4)48 (57.8)36 (46.8)3 (8.1)14 (30.4)260 (52.6)SAE91 (31.8)37 (29.4)23 (27.7)27 (35.1)3 (8.1)14 (30.4)156 (31.6)Treatment-related SAE26 (9.1)11 (8.7)11 (13.3)3 (3.9)1 (2.7)1 (2.2)42 (8.5)TEAE primary reason for permanent discontinuation13 (4.5)7 (5.6)3 (3.6)002 (4.3)18 (3.6)TEAE associated with dose modification190 (66.4)75 (59.5)55 (66.3)46 (59.7)4 (10.8)15 (32.6)308 (62.3)All data are number (%) of patients; d, day; OLE, open-label extension; PCT, physician’s choice of chemotherapy; SAE, serious adverse event; TEAE, treatment-emergent adverse event;aInitiated treatment with talazoparib; monotherapy (1 mg/d) in either the originating or the extension trial;b35 patients who initiated talazoparib 1 mg/d in two of the trials and continued in the OLE are counted only once in the total number of patients Citation Format: Joannes Ettl, Jennifer Litton, Hope S. Rugo, Lida Mina, Miguel Martin, Nicholas Turner, Henri Roché, Zev Wainberg, Johann de Bono, Tiziana Usari, Mohamed Elmeliegy, Silvana Lanzalone, Akos Czibere, Liza DeAnnuntis, Sara A. Hurvitz. An integrated safety analysis of talazoparib monotherapy from five clinical trials (phase 1-3) in advanced cancers [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-29.

In plate rolling, reversing roughing mills are commonly used as a first processing step after casting. They are typically equipped with edger rolls for width reduction. During a rolling pass, lateral asymmetries like temperature gradients or thickness inhomogeneities can cause two major problems. The plate may rotate in the rolling gap and thus move in lateral direction. Another problem is that the plate may leave the mill stand with a cambered shape. In the worst case, these problems entail collisions with the mill stand or other equipment along the roller table. It is an essential control task to avoid such problems. In general, the exit thickness profile and the motion of the plate are controlled by adjusting the roll gap height. The latter has also an influence on the contour shape but, for active control of the plate width and contour shape, the use of edger rolls is more common. This is especially true if the roll gap adjustment is self-retaining, meaning that it cannot be adjusted during a rolling pass. In this work, such a roughing mill and its edger rolls are considered. A mathematical model for the motion and the camber of the plate is derived. Based on this model, a linear quadratic regulator (LQR) for both the plate motion and the resulting camber is developed. It uses the lateral forces of the edgers as control inputs. In a cascaded control structure, these forces are regulated by a subordinate admittance controller. The developed control system is validated in simulation studies.

Background The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade ≥3 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.

Background To evaluate predictive clinico-pathological characteristics on outcome in head and neck melanoma (HNM) in a population-based study with particular emphasis on the prognostic effect of sentinel lymph node biopsy (SLNB), Charlson comorbidity index (CCI) and distinct tumor localisations. Methods Here we primarily describe a retrospective multicenter population-based cohort study with 402 patients having undergone resection with curative intent of HNM between 2010 and 2017. SLNB was used in the diagnosis of 79 HNM patients. Outcome was analyzed, focusing on SLNB, CCI as well as tumor localisation. Overall survival (OAS) und recurrence free survival (RFS) was examined by uni- and multivariate analysis. Results Histopathologically verified lymph node metastasis according to SLNB was associated with impaired RFS in HNM patients (p = 0.004). Especially in higher tumor stages, the sole implementation of SLNB improved survival significantly in the present cohort (p = 0.042). With most of the HNM being located in the face, melanoma of the scalp and neck could be linked to deteriorated patient’s outcome in uni- as well as multivariate analysis (p = 0.021, p = 0.004). Conclusions SLNB is a useful tool in predicting development of distant metastasis after HNM resection with curative intent. Especially in higher tumor stages, performing a SLNB ameliorated survival of HNM patients. Additionally, CCI as well as a distinct tumor localisations in HNM were identified as important risk factors in our population-based cohort study.

Introduction/Background* Due to the improved prognosis of patients with breast cancer, health-related quality of life has become increasingly important. The aim of the study is to evaluate the potential impact of different epidemiological, oncological and treatment parameters on the quality of life at different stages of diagnosis, treatment and follow-up in order to help improve and individualize the support for patients with breast cancer. Methodology Between January 2019 and January 2021, 189 breast cancer patients were included. The quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) and a German questionnaire quantifying psychological distress (FBK-R10) at three distinct time points: At initial diagnosis as well as after six and 12 months. Sociodemographic and clinical data were also included. Result(s)* Both the subjective quality of life and the perceived health condition differed significantly between the three time points (p Conclusion* The quality of life decreased significantly during the first six months after diagnosis, identifying this time as a period of particular need for a multidisciplinary support system. In addition, patients undergoing treatment should receive special attention given their lower quality of life, greater psychological distress and substantially more sexual dysfunction. A significant improvement in quality of life can be observed 12 months after the initial diagnosis. Future studies should focus on how to regain an improved quality of life earlier and how to implement support systems based on the patients’ different needs at different times during the course of the disease.

Background: Loss-of-function mutations in genes encoding components of the homologous recombination DNA damage response (DDR) machinery, notably BRCA1/2, are associated with tumor sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi). Little is known about the potential contribution of tumor alterations in non-DDR genes to modulating sensitivity to PARP inhibitors in the clinic. In EMBRACA, the PARPi TALA improved progression-free survival (PFS) (HR [95% CI] 0.54 [0.41-0.71], P Methods: Baseline tumor tissue from 308 pts (71%; intent-to-treat) was tested by FoundationOne®. To support exploratory identification of tumor gene alterations associated with best vs worst outcomes, pts were mapped into 2 groups: [1] BEST: Pts in TALA arm with OS ≥ 30 mo and duration of treatment ≥ 24 mo, Pts in CT arm with OS ≥ 30 mo; [2] WORST: Pts in TALA or CT arm with a PFS event (PD by Independent Radiological Facility or death) ≤ 12 wks. 2 pts had short PFS but long OS and were initially mapped to both groups but then assigned to BEST and excluded from WORST. Results: Exploratory heat map visualizations of known/likely pathogenic genetic alterations defined by the FoundationOne® gene panel were used to assess differences in genetic alterations between BEST and WORST in TNBC and non-TNBC subpopulations, leading to the identification of MYC and RAD21 as commonly altered genes of high interest. Based on these results showing imbalances in tumor amplification events between BEST and WORST outcome pts, Cox regression analysis was used to explore potential associations of MYC or RAD21 amplification with OS across the evaluable ITT population. In TNBC pts receiving TALA, OS was shorter with MYC amplification than without [HR (95% CI) 1.877 (1.102, 3.196)]. No such association was evident in TNBC pts receiving CT [HR (95% CI) 0.706 (0.303, 1.643)]. In contrast, for non-TNBC pts receiving TALA, no association with OS was evident for MYC amplification versus without [HR (95% CI) 0.603 (0.310, 1.173)], while for pts receiving CT OS was shorter with MYC amplification than without [HR (95% CI) 1.917 (1.037, 3.544)]. RAD21 amplification status was not associated with OS in either TNBC or non-TNBC patients for either treatment arm, although it should be noted that two RAD21 subgroups were very small (n=7 and 11; others had n ≥ 21). Conclusions: Based on these exploratory, retrospective analyses MYC amplification was associated with shorter OS in TNBC pts receiving TALA. This may reflect the role of MYC in positive regulation of genes involved in homologous recombination such as RAD51 (Carey et al, Cancer Res 2018;78(3):742-757). MYC and RAD21 are both located at 8q24 and frequently coamplified in breast cancer (eg, Annunziato et al, Nat Commun. 2019;10(1):397), hence the lack of association of RAD21 amplification with outcome in TNBC suggests that the association of MYC amplification with shorter OS seen in pts receiving TALA may be gene-specific. Further investigation is warranted. Funding: Pfizer TNBCNon-TNBCTALACTTALACTGene AlterationBest n=10Worst n=15Best n=7Worst n=16Best n=17Worst n=11Best n=20Worst n=11MYC amplification0 (0%)7 (47%)2 (29%)6 (38%)5 (29%)1 (9%)3 (15%)5 (46%)RAD21 amplification1 (10%)2 (13%)3 (43%)5 (31%)5 (29%)1 (9%)7 (35%)4 (36%) Citation Format: Johannes Ettl, A. Douglas Laird, Joanne L. Blum, Hope S. Rugo, Sara A. Hurvitz, Miguel Martín, Henri Roché, Young-Hyuck Im, Annabel Goodwin, Rinat Yerushalmi, Tiziana Usari, Silvana Lanzalone, Akos Czibere, Julia Hopkins, Lee A. Albacker, Lida A. Mina, Jennifer K. Litton. A retrospective analysis of association of MYC and RAD21 amplification with final overall survival (OS) data in the phase 3 EMBRACA study with talazoparib [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 PS5-07.

Background: In cardiac arrest survivors, metabolic parameters [pH value, lactate concentration, and base deficit (BD)] are routinely added to peri-arrest factors (including age, sex, bystander cardiopulmonary resuscitation, shockable first rhythm, resuscitation duration, adrenaline dose) to enhance early outcome prediction. However, the additional value of this strategy remains unclear.Methods: We used our resuscitation database to screen all patients ≥18 years who had suffered in- or out-of-hospital cardiac arrest (IHCA, OHCA) between January 1st, 2005 and May 1st, 2019. Patients with incomplete data, without return of spontaneous circulation or treatment with sodium bicarbonate were excluded. To analyse the added value of metabolic parameters to prognosticate neurological function, we built three models using logistic regression. These models included: (1) Peri-arrest factors only, (2) peri-arrest factors plus metabolic parameters and (3) metabolic parameters only. Receiver operating characteristics curves regarding 30-day good neurological function (Cerebral Performance Category 1-2) were analysed.Results: A total of 2,317 patients (OHCA: n = 1842) were included. In patients with OHCA, model 1 and 2 had comparable predictive value. Model 3 was inferior compared to model 1. In IHCA patients, model 2 performed best, whereas both metabolic (model 3) and peri-arrest factors (model 1) demonstrated similar power. PH, lactate and BD had interchangeable areas under the curve in both IHCA and OHCA.Conclusion: Although metabolic parameters may play a role in IHCA, no additional value in the prediction of good neurological outcome could be found in patients with OHCA. This highlights the importance of accurate anamnesis especially in patients with OHCA.

Purpose To illustrate the influence of different socioeconomic factors on the treatment and outcome of patients in Germany with oral cancer. Methods In this retrospective single-center study, 400 patients of our department of oral and maxillofacial surgery with primary cases of oral cancer were included. Preoperative diagnostics, occupational groups, and marital and health insurance status were evaluated. Overall and disease-specific survival were analyzed. Occupations were distinguished in 5 groups (unemployed, physically light workers, physically hard worker, university graduate, and freelancer). Data were adjusted to covariables like tumor size, positive lymph nodes, age, alcohol, or tobacco abuse. Results There was no differences between private and statutory insured patients concerning overall (p = 0.858) or disease-specific survival (p = 0.431). Private insured patients received more preoperative PET-CT (p = 0.046) and had a better dental status (p = 0.006). The occupational groups showed also no differences in survival (p = 0.963). The hospitalization of freelancers was in average 2 days shorter. Physically hard workers were diagnosed with bigger tumors (p = 0.018) and consumed more tobacco and alcohol. The 5-year survival rate of married patients was approximately 20% points better than not married patients, without showing a significant difference over the entire observation time (p = 0.084). Conclusion In our cohort, socioeconomic factors have just a limited influence on the survival or treatment of patients with oral cancer. A sufficient statutory health insurance system is a reasonable explanation for this.

ZusammenfassungDie Weiterentwicklung der Therapien für Frauen mit einem frühen Mammakarzinom schreitet deutlich langsamer voran als bei Patientinnen mit fortgeschrittenem Mammakarzinom und ist zudem zeitlich versetzt zu Entwicklungen beim metastasierten Mammakarzinom. Trotzdem konnten in letzter Zeit deutliche Fortschritte verzeichnet werden. Diese Übersichtsarbeit fasst die jüngsten Entwicklungen vor dem Hintergrund der neuesten Publikationen und Fachkongresse zusammen. Für hormonrezeptorpositive Patientinnen sind neue Aspekte für die Dauer der Antihormontherapie und in Bezug auf den Nutzen von Multigentests veröffentlicht worden. Bei HER2-positiven Patientinnen werden der Stellenwert einer post-neoadjuvanten Therapie und eine Deeskalation der Therapie diskutiert. Bei Patientinnen mit tripel-negativem Mammakarzinom stellt sich die Frage, ob das Wissen um den biologischen Hintergrund einer Defizienz der homologen Rekombination (HRD) dabei hilft, neue Therapien für diesen Subtyp zu entwickeln. Insbesondere die „Nutzung“ einer BRCA1/2-Mutation oder des biologischen Merkmals HRD als potenzielles Therapiemotiv spielen eine Rolle dabei, den Stellenwert der Platintherapie und einer Therapie mit PARP-Inhibitoren zu spezifizieren.

Background In the EMBRACA phase III study (NCT01945775), talazoparib was associated with a significantly prolonged progression‐free survival (PFS) compared with physician's choice of chemotherapy (PCT) in germline BRCA1/2‐mutated HER2‐negative advanced breast cancer (ABC). Herein, the safety profile of talazoparib is explored in detail. Materials and Methods Overall, 412 patients received ≥1 dose of talazoparib (n = 286) or PCT (n = 126). Adverse events (AEs) were evaluated, including timing, duration, and potential overlap of selected AEs. The relationship between talazoparib plasma exposure and grade ≥3 anemia was analyzed. Time‐varying Cox proportional hazard models assessed the impact of dose reductions on PFS. Patient‐reported outcomes (PROs) in patients with common AEs and health resource utilization (HRU) were assessed in both treatment arms. Results The most common AEs with talazoparib were hematologic (195 [68.2%] patients) and typically occurred within the first 3–4 months of receiving talazoparib. Grade 3‐4 anemia lasted approximately 7 days for both arms. Overlapping grade 3‐4 hematologic AEs were infrequent with talazoparib. Higher talazoparib exposure was associated with grade ≥3 anemia. Permanent discontinuation of talazoparib due to hematologic AEs was low (, Talazoparib is a viable option for patients with germline BRCA‐mutated advanced breast cancer. This article presents detailed safety analyses for talazoparib, as a follow‐up to reported results from the EMBRACA trial, to highlight patterns of toxicity compared with chemotherapy and to outline guidelines for management of talazoparib toxicity in clinical practice via dose modifications and/or standard supportive care.

Objectives The aim of this retrospective study was to analyze the early postoperative swallowing outcome in oral cancer patients considering risk factors and localization. Materials and methods Four hundred patients with primary cases of oral cancer were included. Tumors’ locations were categorized into four main groups (central, lateral, anterior and posterior). Swallowing function was evaluated at day 7 after surgery. Results Ninety-eight percent (393/400) of the patients had a swallowing impairment including 41 (10.2%) patients who were unable to swallow. Strong risk factors with p values of 0.001 were tumor size, nodal stage, tracheotomy, insufficient dental status and reconstruction with a flap. The inability to swallow was increased at T1 und T2 patients, if they were reconstructed with a flap compared to patients who had a primary wound closure (p = 0.04). Decreased swallowing function was determined if the tumor was located central (OR = 1.8; p = 0.141) and additionally posterior (OR = 5.8; p = 0.110). Inability to swallow, even at that early point in time, (p = 0.001) was as significant as tumor size (p = 0.009) and nodal stage (p = 0.020), referring to overall survival. Conclusion The impact of early dysphagia should not be underestimated. By considering swallowing impairment at the primary therapy patients can profit concerning survival and comorbidity.

Die Behandlung von Patientinnen mit fortgeschrittenem Mammakarzinom hat sich in den letzten Jahren weiterentwickelt. Zusätzlich zum Therapiefortschritt in den etablierten Subgruppen (Hormonrezeptor- und HER2-Status) gibt es nun Therapien, die sich an einzelnen molekularen Charakteristika orientieren, wie zum Beispiel die PARP-Inhibitortherapie bei BRCA-mutierten Patientinnen. Zusätzlich dazu sind Tests in der Entwicklung, die innerhalb von Subgruppen weitere Marker etablieren sollen, um die Wirksamkeit einer Therapie vorherzusagen. Die PI3K-Mutationstestung bei HER2-negativen, hormonrezeptorpositiven Tumoren, und die PD-L1-Testung von Immunzellen bei triple-negativen Tumoren werden voraussichtlich in der klinischen Praxis etabliert, um Patientinnen für die jeweiligen Therapien auszuwählen. Mit neuen Therapieansätzen treten auch neue Nebenwirkungen auf. Das Management dieser Nebenwirkungen ebenso wie die der klassischen Therapien (supportive Therapie) ist mit der Einführung neuer Behandlungen essenziell, um die Lebensqualität der Patientinnen zu erhalten. Das Wissen über Maßnahmen zur Erhaltung und Verbesserung der Lebensqualität hat in den letzten Jahren deutlich zugenommen. Lifestyle-Faktoren sollten dabei ebenso Berücksichtigung finden wie moderne Therapieverfahren. Diese Übersichtsarbeit fasst die neuesten Studien und Veröffentlichungen zusammen und bewertet sie in Bezug auf die Relevanz für die klinische Praxis. The treatment of patients with advanced breast cancer has developed further in recent years. In addition to therapeutic progress in the established subgroups (hormone receptor and HER2 status), there are now therapies which are geared to individual molecular characteristics, such as PARP inhibitor therapy in BRCA-mutated patients. In addition to this, tests are being developed which are intended to establish additional markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormone-receptor-positive tumours and PD-L1 testing of immune cells in triple-negative tumours are expected to become established in clinical practice in order to select patients for the respective therapies. With new therapeutic approaches, new adverse effects also appear. The management of these adverse effects, just as those of classical therapy (supportive therapy), is essential with the introduction of new treatments in order to preserve patientsʼ quality of life. Knowledge regarding measures to preserve and improve quality of life has significantly increased in recent years. Lifestyle factors should be taken into account, as should modern therapeutic methods. This review summarises the latest studies and publications and evaluates them in regard to the relevance for clinical practice.

ZusammenfassungDie Behandlung von Mammakarzinom-Patientinnen in der kurativen Situation ist in vielfacher Hinsicht besonders. Hierbei ist die lokale Therapie mit Operation und Strahlentherapie zentraler Aspekt der Behandlung. Ziel ist eine komplette Elimination aller Tumorzellen am Ort der Primärerkrankung bei gleichzeitigem Bestreben, die Langzeitfolgen so gering wie möglich zu halten. Die immer weitere Reduktion der Radikalität der Lokaltherapie steht auch weiterhin im Blickpunkt. In Bezug auf die Systemtherapie haben sich in den letzten beiden Jahrzehnten Chemotherapien mit Taxanen, Anthrazyklinen und teilweise auch platinhaltigen Chemotherapien etabliert. Der Kontext der Nutzung wird immer genauer definiert. Ebenso gibt es bei der antihormonellen Therapie Fragen, die auch nach Einführung der Aromatasehemmer immer noch weiter definiert werden müssen, wie beispielsweise die Länge der Therapie oder die ovarielle Suppression bei prämenopausalen Patientinnen. Letztendlich soll die Behandlung von frühen Mammakarzinom-Patientinnen immer personalisierter werden. Prognostische genexpressionistische Tests könnten möglicherweise Therapieentscheidungen unterstützen. Ebenso muss überlegt werden, wie ein möglicher Einsatz von neuen Therapien, wie Checkpoint-Inhibitoren und CDK4/6-Inhibitoren, in der Praxis aussehen könnten, sobald hier Studienergebnisse vorliegen. Diese Übersichtsarbeit beschäftigt sich mit den Hintergründen zu aktuellen Abstimmungen, die das internationale St.‑Gallen-Expertenpanel in Wien 2019 für aktuelle Fragen in der Behandlung von Mammakarzinom-Patientinnen in der kurativen Situation vorgenommen hat.

The treatment of breast cancer patients in a curative situation is special in many ways. The local therapy with surgery and radiation therapy is a central aspect of the treatment. The complete elimination of tumour cells at the site of the primary disease must be ensured while simultaneously striving to keep the long-term effects as minor as possible. There is still focus on the continued reduction of the invasiveness of local therapy. With regard to systemic therapy, chemotherapies with taxanes, anthracyclines and, in some cases, platinum-based chemotherapies have become established in the past couple of decades. The context for use is being continually further defined. Likewise, there are questions in the case of antihormonal therapy which also still need to be further defined following the introduction of aromatase inhibitors, such as the length of therapy or ovarian suppression in premenopausal patients. Finally, personalisation of the treatment of early breast cancer patients is also being increasingly used. Prognostic tests could potentially support therapeutic decisions. It must also be considered how the possible use of new therapies, such as checkpoint inhibitors and CDK4/6 inhibitors could look in practice once study results in this regard are available. This overview addresses the backgrounds on the current votes taken by the international St. Gallen panel of experts in Vienna in 2019 for current questions in the treatment of breast cancer patients in a curative situation.

Purpose: To assess talazoparib activity in germline BRCA1/2 mutation carriers with advanced breast cancer. Patients and Methods: ABRAZO (NCT02034916) was a two-cohort, two-stage, phase II study of talazoparib (1 mg/day) in germline BRCA mutation carriers with a response to prior platinum with no progression on or within 8 weeks of the last platinum dose (cohort 1) or ≥3 platinum-free cytotoxic regimens (cohort 2) for advanced breast cancer. Primary endpoint was confirmed objective response rate (ORR) by independent radiological assessment. Results: We enrolled 84 patients (cohort 1, n = 49; cohort 2, n = 35) from May 2014 to February 2016. Median age was 50 (range, 31–75) years. Triple-negative breast cancer (TNBC) incidence was 59% (cohort 1) and 17% (cohort 2). Median number of prior cytotoxic regimens for advanced breast cancer was two and four, respectively. Confirmed ORR was 21% [95% confidence interval (CI), 10–35; cohort 1] and 37% [95% CI, 22–55; cohort 2]. Median duration of response was 5.8 and 3.8 months, respectively. Confirmed ORR was 23% (BRCA1), 33% (BRCA2), 26% (TNBC), and 29% (hormone receptor–positive). The most common all-grade adverse events (AE) included anemia (52%), fatigue (45%), and nausea (42%). Talazoparib-related AEs led to drug discontinuation in 3 (4%) patients. In an exploratory analysis, longer platinum-free interval was associated with higher response rate in cohort 1 (0% ORR with interval 6 months). Conclusions: Talazoparib exhibited promising antitumor activity in patients with advanced breast cancer and germline BRCA mutation.

The identification of the stress-strain curve of metal strips is a common task in the metals industry. As an alternative to commonly used tensile test machines, an inexpensive, model-based optical ...

ZusammenfassungIn der Prävention und Behandlung des frühen Mammakarzinoms sind über die Jahre immer wieder kleine, aber bedeutsame Fortschritte gemacht worden. In der Prävention gewinnen die sogenannten Panel-Gen-Analysen immer mehr an Bedeutung, da das durch die getesteten Gene bedingte Risiko immer besser verstanden wird und somit Konzepte für die Integration in die Krankenversorgung erarbeitet werden können. In der adjuvanten Situation konnte die erste Studie in der sogenannten postneoadjuvanten Situation bei fehlender pathologischer Komplettremission nach Trastuzumab oder Pertuzumab + Trastuzumab eine deutliche Verbesserung der Prognose zeigen. Weitere Studien mit diesem postneoadjuvanten Therapiekonzept werden zurzeit noch durchgeführt. Die CDK4/6-Inhibitoren, die in der metastasierten Situation eine deutliche Verbesserung des progressionsfreien Überlebens gezeigt hatten, werden zurzeit in der adjuvanten Situation in großen Therapiestudien getestet. Diese und weitere neue Daten zur Behandlung oder Prävention des primären Mammakarzinoms werden in dieser Übersichtsarbeit vor dem Hintergrund aktueller Studien vorgestellt.

Background Studies leading to the approval of trastuzumab emtansine (T-DM1) have been conducted without pertuzumab as previous therapy. Therefore data about patient characteristics and the efficacy of T-DM1 after a treatment with pertuzumab is scarce. Aim of this study was to analyze a real world patient cohort of advanced breast cancer (aBC) patients, who were treated with T-DM1 after a treatment containing pertuzumab in the metastatic setting with regard to patient characteristics and progression free survival (PFS). Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for metastatic breast cancer patients with focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible for this registry. Collected data comprises all relevant patient and tumor characteristics, therapies, adverse events, quality of life, patient reported outcomes, response and survival (PFS/OS). Here we report on the patient characteristics and PFS data for HER2 positive patients treated with T-DM1 after a treatment with pertuzumab. Patients had to be included before or at the beginning of the T-DM1 therapy. Results A total of 58 patients could be identified, who were suitable for the analysis. Of those 34 were treated in the second line, 14 in the third line and 10 in the fourth line or higher. Most of the pertuzumab therapies before T-DM1 were conducted in first line (n=46; 79.3%). Median PFS for all patients was 4.8 months (95% CI: 3.0-7.8 months). Median PFS for patients treated in the 3rdline and 4thline or higher was 4.2 months(95%CI: 2.3 - NA) and 4.0 months (95%CI: 1.8-N.A.), respectively. In patients treated 2ndline with T-DM1 PFS was 7.7 months (95%CI: 2.8 – 12.2). Conclusion T-DM1 is effective as 2ndand further line therapy following pretreatment with pertuzumab. Overall PFS was about 5 months with 7.7 months as 2nd-line therapy. The PFS in higher therapy lines might be shorter. As the sample size of this real world cohort was rather low and analyses have to be considered exploratory, this data need to be confirmed in studies with a larger sample size. Citation Format: Schneeweiss A, Lux MP, Hartkopf AD, Volz B, Kolberg H-C, Hadji P, Tesch H, Haeberle L, Ettl J, Lüftner DI, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Overkamp F, Huober J, Taran F-A, Janni W, Wallwiener D, Brucker SY, Fasching PA, Fehm TN. Progression free survival (PFS) and overall survival (OS) of patients treated with trastuzumab emtansine (T-DM1) after previous treatment with pertuzumab in patients with advanced breast cancer (NCT02338167) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-22.

Purpose: This analysis describes comprehensive real-world data concerning the use of anti-HER2 therapies in HER2 positive metastatic breast cancer (MBC). Specifically, it describes the therapy patterns of treatments with trastuzumab (TZM), pertuzumab+trastuzumab (PTZ/TZM), lapatinib (LAP) and trastuzumab emtansine (T-DM1). Methods: The PRAEGNANT study is a real-time, real-world registry for patients with MBC. Patients can be registered for PRAEGNANT at any time during the course of their metastatic disease and are followed up until death. All therapy lines are documented. This analysis presents the utilization of anti-HER2 therapies as well as therapy sequences. Results: Of 1936 patients within PRAEGNANT at the time of database closure 451 were HER2 positive (23.3%). Within the analysis set (417 patients after an unilateral breast cancer diagnosis), of which 53% were included in PRAEGNANT in the 1stline setting, 241 were treated with TZM (58%), 237 with PTZ (57%), 85 with LAP (20%) and 125 with T-DM1 (30%) during the course of their therapies. The sequence PTZ/TZMàT-DM1 was given to 51 patients (12%). Worse ECOG, negative hormone receptor status, and visceral or brain metastases were associated with a more frequent use of this therapy sequence. Most patients received T-DM1 after a therapy with pertuzumab. Conclusions: Both novel therapies (PTZ/TZM and T-DM1) are utilized in a high proportion of HER2 positive breast cancer patients. As most patients receive T-DM1 after pertuzumab real world data might help to understand whether this sequence has similar efficacy like in the approval study. Citation Format: Lux MP, Hartkopf AD, Huober J, Volz B, Taran F-A, Overkamp F, Hadji P, Tesch H, Haeberle L, Ettl J, Lueftner DI, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Fasching PA, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A, Kolberg H-C. Therapy landscape of patients with metastatic, HER2 positive breast cancer - Data from the real world breast cancer registry PRAEGNANT (NCT02338167) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-37.

Background: In node negative and 1-3 positive nodes breast cancer patients with hormone receptor positive (HR+), HER2-negative (HER2-) early-stage breast cancer the indication for chemotherapy is based on clinical and pathologic risk stratification (tumor size, nodal status, grading, quantitative ER, progesterone receptor and Ki67). For further decision-making, the EndoPredict test, which combines a molecular signature with the clinical risk factors tumor size and nodal status, stratifies patients into “low risk" or “high risk” groups. Level I-B- evidence demonstrates, that EndoPredict predicts the 10 year cumulative risk of relapse and metastases in patients with HR+/HER2- primary breast cancer with endocrine treatment. Aim: In the RESCUE-Trial we document distant metastasis-free survival (DMFS), disease free survival (DFS) and overall survival (OS) events in patients who had an EndoPredict test. The primary objective is to show that 10-year DMFS of patients tested as “low risk” by EndoPredict and treated with adjuvant endocrine therapy alone is >90 %. Secondary endpoints among others include DMFS, DFS, OS in patients with EPclin “low risk” versus “high risk”. Also the proportion of patients whose treatment was concordant and non-concordant with EndoPredict test results, will be analyzed for survival. The prognostic performance of classical prognostic factors (like tumor size, nodal status, grading, quantitative ER, progesterone receptor and Ki67 level) with respect to survival will also be assessed. Eligibility: Patient with HR+/HER2- primary invasive breast cancer stage I/II and T1 to T3 with 0 to 3 positive lymph nodes will be eligible, if they had an EndoPredict test within three months before inclusion. Methods: The EndoPredict test results, tumor board decision and anti-tumor therapy will be assessed. After one year, annually (for 10 years), patients will be evaluated for treatment compliance, recurrence, metastases, and survival. The primary endpoint will be analyzed by a Kaplan-Meyer estimate for which a one-sided lower 95 % confidence interval will be given. Several secondary endpoints will be assessed in three interim analyses after completion of the 1st, 3rd, 5th year and then finally after 10 years. Accrual: Start of accrual is planned for July 2018. At least 26 sites in Germany and one site in Switzerland will be active. Sponsor: The study is sponsored by the North-Eastern-German Society of Gynecological Oncology (NOGGO) e.V. Contact Information: For further information, contact NOGGO via studies@noggo.de or the leading physician Dr. Johannes Ettl via johannes.ettl@tum.de. Citation Format: Ettl J, Blohmer J-U, Denkert C, Keller M, Klein E, Kronenwett R, Neuser P, Paepke S, Schade-Brittinger C, Schnuppe K, Untch M, Wittenberg M, Kiechle M. RESCUE: Reaching for Evidence-baSed Chemotherapy Use in Endocrine sensitive breast cancer - A prospective health care study on risk assessment by the clinicomolecular test EndoPredict® and long-term patient outcome in early luminal breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-12-03.

Background: Every seventh to eighth woman is diagnosed with breast cancer in her life. Next to surgery and radiotherapy most of them receive (neo)adjuvant chemotherapy, which comes along with adverse effects. Complementary and alternative medicine (CAM) like Reiki can reduce these effects. Reiki is a Far Eastern method that promotes healing on a physical, mental and emotional level and activates self-healing powers. REASSURE examines the effects of Reiki on quality of life and taxane-induced polyneuropathy during chemotherapy. Methods: REASSURE is a prospective, randomized, controlled, two-armed clinical trial, in which patients with breast cancer receive chemotherapy and Reiki (18 times) or chemotherapy and sport (18 times). During chemotherapy and before and after every Reiki- or sport-session the patients fill out standardized questionnaires (e.g. FACT/GOG-NTX Version 4). Primary endpoint is the comparison of quality of life at the end of chemotherapy between Reiki and sport based on the FACT/GOG-NTX score by T-Test. Secondary endpoint is the comparison of the taxane-induced polyneuropathy at the end of chemotherapy between the two groups. Also short-term effects before and after the Reiki- and sport-session will be examined. A power of 1-β = 0.8, a bilateral probability of error of α = 0.05, a minimum relevant difference deltaθ = 4 and a pooled standard deviation of 11 for the two-sided T-Test result in case numbers of 2 x 120 = 240 patients. Conclusion: REASSURE is the most comprehensive prospective study to the effects and the feasibility of Reiki on breast cancer patients during chemotherapy so far. Since July 2015, 138 patients have been enrolled at three different centers. Currently 63 patients in total (39 patients of the Reiki-group and 24 patients of the sport-group) have completed the study. 24 Reiki-patients and 36 sport-patients are counted as dropouts because of reasons like incomplete data records, discontinuation of chemotherapy, not enough time or energy for Reiki- or sport-sessions or other reasons. Sponsor: This is a collaborative study of the Department of Obstetrics and Gynecology, Klinikum rechts der Isar, Technische Universität München (TUM), Munich, Germany, Rotkreuzklinikum München, Frauenklinik, Munich, Germany, Department of Gynaecology, Städtisches Klinikum München Harlaching, Munich, Germany and the ProReiki – der Berufsverband e.V., Berlin, Germany. Contact Information: For further information contact Sophie Katzendobler via sophie.katzendobler@gmail.com or the leading physician Dr. Johannes Ettl via johannes.ettl@tum.de. Citation Format: Katzendobler S, Haunreiter L, Zander L, Schmidt R, Andrulat A, Münch K, Hanusch C, Napieralski R, Petri I, Ettl J. REASSURE- Effects of Reiki as supportive treatment during chemotherapy of breast cancer: A prospective, randomized, controlled clinical trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-05-05.

Background During the last decades the treatment of advanced breast cancer (ABC) patients has improved due to a variety of new treatment strategies. Nevertheless, many ABC patients are faced with limited prognosis, and their treatment remains a challenge. New targeted therapies complement the well-established treatment options for ABC (CDK4/6 inhibition, anti-endocrine, chemotherapy, antibody based and bone related therapies), leading to improved treatment regimens tailored to the needs of special patient sub-populations. SPECIFIC AIMS/TRIAL DESIGN The PRAEGNANT network study is conducted as an academic, prospective registry and diagnostic translational study, accompanied by biomaterial collection. The pilot phase in more than 60 centers aims at including 3500 ABC patients. The primary objective is to discover biomarkers, which predict progression free survival (PFS). Secondary objectives include overall survival (OS), breast cancer specific survival, objective response rate, patient reported outcomes (PRO), description of therapies used in the metastatic setting, therapy adherence, health economics for patients with ABC, incidence of (serious) adverse events and big data/ machine learning algorithms. The exploratory objectives comprise correlations of gene alterations and their influence on OS, PFS, side effects and PRO. Exploratory biomarkers are assessed at baseline and at every change of therapy. These biomarkers include gene expression profiling of the primary tumor and corresponding metastasis, somatic mutations (measured in the tumor and in circulating tumor DNA), germline genetic variations, epigenetic changes and miRNA variations. Furthermore, plasma and serum markers are assessed. If actionable molecular alterations are detected patients are informed and recruited into suitable studies if available. ELIGIBILITY CRITERIA: Any adult patient (>18 years) with the diagnosis of ABC and who is willing and able to sign the informed consent can be enrolled. STATISTICAL METHODS/TARGET ACCRUAL: The PRAEGNANT study as a prospective real world registry and diagnostic translational study aims to identify biomarkers in ABC patients, which may predict PFS. Target accrual for the pilot phase is 3500 patients. Each patient will be documented for up to 36 months with an estimated median PFS for all patients of 11 months across all treatment lines. Citation Format: Müller V, Huober J, Volz B, Overkamp F, Kolberg H-C, Hadji P, Haeberle L, Ettl J, Hartkopf AD, Lux MP, Lüftner DI, Wallwiener M, Taran F-A, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Lermann J, Abenhardt A, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Fehm TN, Brucker SY, Wallwiener D, Schneeweiss A, Fasching PA, Tesch H. PRAEGNANT - Real world evidence, translational research, big and smart data: A prospective academic translational research network for the optimization of the oncological health care quality in the adjuvant and advanced/ metastatic setting (NCT02338167) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-11-02.

Background: Talazoparib (TAL) prevents DNA damage repair by inhibiting poly (ADP-ribose) polymerase (PARP) enzymes and trapping PARP on DNA, resulting in cell death in BRCA1/2-mutated cells. Methods: EMBRACA is an open-label, randomized, 2-arm phase 3 trial in which efficacy and safety of TAL (1 mg/d) were compared with physician's choice of therapy (PCT; capecitabine, eribulin, gemcitabine, vinorelbine) in patients (pts) with locally advanced or metastatic breast cancer (ABC) and a germline BRCA mutation (gBRCAm). Outcomes were assessed by region of the world (North America [NA]; Europe [EU]; rest of world [ROW]). Progression-free survival (PFS), objective response rate (ORR), and clinical benefit rate (CBR) at 24 wks were assessed; safety was also assessed. Results: 431 pts were randomized 2:1. Pt characteristics were well balanced, although a higher percentage of pts in ROW had more severe disease (eg, triple-negative breast cancer [TNBC], Disease-free interval [DFI] Table 1CategoryNA* (N=156)EU* (N=190)ROW* (N=85)Mean age, years49.049.244.2Race, % White76.971.152.9Black5.8-3.5Asian5.8-42.4Not reported-27.4-TNBC, %424447BRCA1**, %414748BRCA2**, %595352DFI Conclusions: In pts with gBRCAm ABC, TAL demonstrated significant improvements in clinical outcomes compared with PCT regardless of the region of the world in which they lived. However, slight differences among the regions in baseline characteristics were noted, possibly due to regional variation in diagnosis and detection of gBRCAm ABC as well as different treatment paradigms for metastatic breast cancer. Funding: Medivation LLC, acquired by Pfizer. Citation Format: Mina L, Lee K-H, Gonçalves A, Woodward N, Hurvitz SA, Diab S, Yerushalmi R, Goodwin A, Moreira Costa Zorzetto M, Kim S-B, Czibere A, Tudor IC, Gauthier E, Litton JK, Ettl J. EMBRACA: Efficacy and safety of talazoparib or physician's choice of therapy in patients with advanced breast cancer and a germline BRCA1/2 mutation: A regional analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-18-12.