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Background In the current pandemic regarding the infection with the SARS-CoV-2-virus and COVID-19 as the disease, concerns about pregnant women, effects on childbirth and the health of the newborn remain high. Initially, due to the early manifestation of the disease in younger patients, high numbers of COVID-19 patients in women needing peripartum care were expected. Objective This article aims to provide a general overview over the beginning of the pandemic as well as the second wave of infections in Germany and Switzerland, regarding SARS-CoV‑2 positive pregnant women hospitalized for childbirth. We therefore launched a registry to gain timely information over the dynamic situation during the SARS-CoV‑2 pandemic in Germany. Material and methods As part of the COVID-19-related Obstetric Anesthesia Longitudinal Assessment (COALA) registry, centers reported weekly birth rates, numbers of suspected SARS-CoV‑2 cases, as well as the numbers of confirmed cases between 16 March and 3 May 2020. Data acquisition was continued from 18 October 2020 till 28 February 2021. The data were analyzed regarding distribution of SARS-CoV‑2 positive pregnant women hospitalized for childbirth between centers, calendar weeks and birth rates as well as maternal characteristics, course of disease and outcomes of SARS-CoV‑2 positive pregnant women. Results A total of 9 German centers reported 2270 deliveries over 7 weeks during the first wave of infections including 3 SARS-CoV‑2 positive cases and 9 suspected cases. During the second survey period, 6 centers from Germany and Switzerland reported 41 positive cases out of 4897 deliveries. One woman presented with a severe and ultimately fatal course of the disease, while another one needed prolonged ECMO treatment. Of the women 28 presented with asymptomatic infections and 6 neonates were admitted to a neonatal intensive care unit for further treatment. There was one case of neonatal SARS-CoV‑2 infection. Conclusion The number of pregnant women infected with SARS-CoV‑2 was at a very low level at the time of delivery, with only sporadic suspected or confirmed cases. Due to the lack of comprehensive testing in the first survey period, however, a certain number of asymptomatic cases are to be assumed. Of the cases 68% presented as asymptomatic or as mild courses of disease but the data showed that even in young healthy patients without the presence of typical risk factors, serious progression can occur. These outcomes should raise awareness for anesthesiologists, obstetricians, pediatricians and intensive care physicians to identify severe cases of COVID-19 in pregnant women during childbirth and to take the necessary precautions to ensure the best treatment of mother and neonate. The prospective acquisition of data allowed a timely assessment of the highly dynamic situation and gain knowledge regarding this vulnerable group of patients.

Objective: We aimed to evaluate real-world data for the use of fractional CO2 laser therapy for treating symptoms of vulvovaginal atrophy (VVA). Background: VVA is widespread and can reduce the pat...

Die operative Versorgung bei Brustkrebs betrifft die Brust und die Lymphabflusswege. Verbesserte Fruherkennungsmasnahmen und neoadjuvante Therapien haben einen Beitrag zur Deeskalation der operativen Therapie geleistet. Dennoch kann es Grunde fur die Entfernung des Drusenkorpers geben. Um ein kosmetisch zufriedenstellendes Ergebnis zu erreichen, stehen verschiedene onkoplastische und rekonstruktive Masnahmen zur Verfugung. Das Ziel dieser Arbeit ist es, eine Ubersicht uber die operative Versorgung bei Mammakarzinom zu geben. Dabei stehen auch rekonstruktive Moglichkeiten und ausgewahlte Komplikationen im Fokus. Die operative Versorgung bei Patientinnen mit Mammakarzinom ist sehr vielfaltig. Die Techniken wurden ebenso wie das Komplikationsmanagement stetig weiterentwickelt. Auch wenn die onkologische Sicherheit an oberster Stelle steht, kann so eine individuelle Beratung und Losung fur die Patientin gefunden werden.

ZusammenfassungBei neuen Therapieansätzen des Mammakarzinoms sind insbesondere bei Patientinnen mit HER2-positivem und HER2-negativem/hormonrezeptorpositivem (HR+) Mammakarzinom in den letzten Jahren deutliche Fortschritte gesehen worden. Bei HER2-positiven Tumoren müssen in dem Zusammenhang Pertuzumab, T‑DM1, Neratinib und bald auch Tucatinib und Trastuzumab-Deruxtecan (beide in Europa noch nicht zugelassen) genannt werden. Bei den Patientinnen mit HER2−/HR+-Mammakarzinom sind insbesondere die CDK4/6-Inhibitoren und der PIK3CA-Inhibitor Alpelisib zu nennen. Weitere, neue Therapien wie Akt-Kinase-Inhibitoren und orale SERDs (selective estrogen receptor down-regulators) werden bereits in laufenden klinischen Studien untersucht. Nicht nur bei den HER2-positiven Tumoren halten die Therapien Einzug in die kurative, (neo-) adjuvante Therapiesituation, sondern es wurde nun eine erste positive Studie mit Abemaciclib in der adjuvanten Situation vorgestellt. Bei Patientinnen mit einem triple-negativen Mammakarzinom ist nach vielen Jahren mit negativen Studienergebnissen mit dem Trop-2-Antikörper-Wirkstoff-Konjugat (antibody drug conjugate, ADC) Sacituzumab-Govitecan eine randomisierte Studie veröffentlicht worden, die einen deutlichen Therapiefortschritt bedeuten kann. Diese Übersichtsarbeit beschreibt die neuesten Entwicklungen beim Mammakarzinom nach dem ESMO-Kongress 2020.

BACKGROUND/AIM There is a lack of data concerning the surgical treatment of locally advanced squamous cell carcinoma of the uterine cervix (LACC) with neoadjuvant and adjuvant chemotherapy (NACT, ACT) as well as total mesometrial resection (TMMR). The aim of the study was to present a novel approach for treating LACC using a tumor response score for NACT. PATIENTS AND METHODS A total of 12 patients with LACC were treated with NACT [cisplatin, ifosfamide, paclitaxel (TIP)], TMMR and ACT containing TIP. To measure the response during NACT, we scored i) the maximum tumor diameter (maxTD) in gynecological examination, ii) the MRI for radiologic maxTD, iii) the tumor volume and iv) the squamous cell carcinoma antigen before and after two applications of TIP. RESULTS TIP reduced all score-parameters in 10 of 12 patients (p

ZusammenfassungDie Therapie Schwangerer mit irreversiblem Hirnfunktionsausfall ist ein Extrembeispiel nicht nur für die Möglichkeiten moderner Intensivmedizin, sondern auch für die daraus resultierenden ethischen, sozialen und rechtlichen Spannungsfelder, die für Mediziner kein vertrautes Terrain sind. Im Folgenden wird der Fall einer in der 9. SSW verunfallten Patientin mit infauster Prognose bei massivem Schädel-Hirn-Trauma und anamnestischem Wunsch zur Organspende vorgestellt. Vor diesem Hintergrund werden anhand ausgewählter Fälle aus der Literatur verschiedene Aspekte beleuchtet: die Frage der Therapiezielfestlegung, insbesondere Palliation vs. Fortführung; die Implikationen einer Hirntoddiagnostik; betreuungsrechtliche Überlegungen; Einbindung der Angehörigen, v. a. des Kindsvaters; Dynamiken im Behandlungsteam sowie schließlich die Frage einer möglichen Organspende. Das Fallbeispiel verdeutlicht zudem, dass auch bei denkbar ungünstigen Rahmenbedingungen und dem Zusammenkommen scheinbar unvereinbarer Faktoren eine Schwangerschaft überraschend unbeeinträchtigt ausgetragen werden kann. Die recherchierten Fakten und Erwägungen sowie die zitierte weiterführende Literatur in diesem Artikel sollen einen Überblick über potenzielle Dilemmata verschaffen und als fundierter Ausgangspunkt für ähnlich gelagerte Fälle dienen.

Zusammenfassung Hintergrund Infolge der zunehmend individualisierten, multimodalen Therapie gibt es eine Vielzahl von potenziellen, therapieinduzierten Folgestörungen bei Mammakarzinom-Patientinnen. Die zunehmend verbesserte Langzeitprognose, das häufig junge Erkrankungsalter und die hohe Inzidenz der Erkrankung unterstreichen die Bedeutung dieser teils chronischen Nebenwirkungen für die berufliche und soziale Teilhabe. Methoden Im Rahmen dieser retrospektiven Analyse wurden bei 8000 Brustkrebspatientinnen (Durchschnittsalter 55,7 ± 10,4J) klinische Parameter und therapieinduzierte Toxizitäten und Folgestörungen im zeitlichen Verlauf analysiert und mit Daten aus der Literatur verglichen. Ergebnisse In 23,6% der Fälle wurde eine Mastektomie, in 89% eine Radiatio durchgeführt. Zudem erfolgte in den meisten eine zusätzliche systemische Therapie (57,6% CTX, 15,1% anti-Her2, 71% Antihormontherapie). In 8,1% lag ein Rezidiv bzw. eine metastasierte Erkrankung vor. Als häufigste Folgestörungen infolge der multimodalen Therapie ließen sich Kraftlosigkeit/Fatigue (73,6%), Schlafstörungen (51,9%), CIPN (33%), Lymphödeme (13,9%) und medikamentös-induzierte Arthralgien (24,8%) nachweisen. Zudem berichteten 60,4% der Frauen über einen hohen, psychischen Distress. Während kurz nach Akutbehandlung (AHB) signifikant häufiger CTX-induzierte Toxizitäten dokumentiert wurden (Leukopenie, p Diskussion Nach multimodaler Brustkrebstherapie lassen sich zwischen AHB- gegenüber Patientinnen im Regelheilverfahren teils signifikant unterschiedliche rehabilitationsrelevante Folgestörungen dokumentieren. Die Vielzahl und Vielfältigkeit somatischer sowie psychovegetativer Störungen unterstreichen die Notwendigkeit nach individualisierten, multimodalen Therapiekonzepten in der onkologischen Rehabilitation.

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.

Background: In MONALEESA-3 and MONALEESA-7 trials, ribociclib (RIB, a selective CDK4/6 inhibitor) in combination with endocrine therapy (aromatase inhibitor [AI] or fulvestrant [FUL]) demonstrated a significant prolongation of overall survival among patients with breast cancer (BC), regardless of menopausal status and treatment-line. In the premenopausal or perimenopausal women, RIB + AI/FUL should be combined with a luteinizing hormone-releasing hormone agonist. The real-world evidence for the effectiveness, safety, and tolerability of RIB + AI/FUL in the routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a prospective, non-interventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal women (planned, n = 3020) treated with RIB + AI/FUL, or endocrine monotherapy (ET), or chemotherapy (CT) as the first-line treatment for HR+/HER2- aBC in accordance with German guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. Updated data on baseline demographics and safety analysis will be presented. Additionally, first experience with CANKADO, an innovative digital and patient-friendly application for electrocardiogram (ECG) measurement, are described. By combining this app to Kardia mobile (AliveCor’s single lead device), single-lead ECG can be recorded and sent via the CANKADO app for a cardiologist to read over. The cardiologist reviews the measurements, and reports the corrected QT interval by Fredericia (QTcF) results towards the trial site. Impact of the use of CANKADO onto the clinical routine will be analyzed. Results: For the second interim analysis, 1141 patients were enrolled until July 12th, 2019, while the full analysis set comprised 813 patients (Table 1). Median duration of RIB exposure in patients on RIB + AI/FUL vs total population was 151 vs 150 days respectively. At cut-off date, patients received first-line (89%, n = 1016), second-line (7%, n = 82), and third-line treatments (1%, n = 11). A starting dose of 600 mg per day for RIB in the first-line setting was seen in most of the patients (85%); data of second-line patients will be reported later. The first-line mean daily dose of RIB was 451.6 mg/day RIB was prescribed mainly in combination with letrozole (75%), fulvestrant (12%), anastrozole (7%), and exemestane (6%). A total of 62% of patients in the study were documented as therapy-naïve for ET. Of 424 patients with early breast cancer, 129 (30%) had documented prior CT without ET. The most common all-grade adverse events frequently noted in RIB + AI/FUL cohort in comparison with other cohorts were nausea (RIB [19%] vs ET [9%] vs CT [11%]), neutropenia (19% vs 1% vs 10%), fatigue (17% vs 9% vs 14%), and leukopenia (14% vs 4% vs 12%). The usage of CANKADO application to assess QTcF was initiated in the year 2019 and first data will be presented. Conclusion: RIBANNA study showed diverse population characteristics among the patients who received RIB treatment in a real-world setting. The third interim analysis is planned in October 2020, and the updated baseline data, information on safety, digital ECG measurement using CANKADO application will be presented. Baseline Demographic Characteristics as of Second Interim AnalysisDemographic VariableRIB + AI/FUL (n = 658)Endocrine Therapy (n = 78)Chemotherapy (n = 77)Mean age, years (SD)67 (11)72 (12)62 (10)Mean time since initial diagnosis, years6.17.23.6T stage at baseline*, n (%)TX204 (31)28 (36)18 (23)T0+T1132 (20)12 (15)11 (14)T2-T4302 (46)35 (45)42 (54)N stage at baseline*, n (%)NX212 (32)29 (37)28 (36)N0+N1317 (48)36 (46)35 (46)N2+N3108 (16)10 (13)8 (10)M stage at baseline*, n (%)MX6 (1)0 (0)0 (0)M018 (3)1 (1)1 (1)M1616 (94)75 (96)71 (92)Metastatic location at baseline*, n (%)CNS, liver, lungs258 (39)14 (18)42 (54)Bone only181 (28)42 (54)11 (14)Skin, lymph nodes, other149 (23)16 (20)14 (18)*Remaining cases are missing.CNS, central nervous system. Citation Format: Achim Wöckel, Cosima Brucker, Thomas Decker, Jörg Falbrede, Helmut Forstbauer, Thomas Göhler, Oliver Hoffmann, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Diana Lüftner, Frederik Marmé, Arnd Nusch, Toralf Reimer, Christian Roos, Marcus Schmidt, Rudolf Weide, Peter Fasching. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study [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 PS10-16.

Introduction Invasive lobular breast cancer (ILC) is with 5-10% the second most common histologic type of invasive breast cancer after invasive ductal breast cancer (IDC). ILC differs from IDC, for example in its metastatic pattern. However, guidelines do not provide special treatment recommendations for this subtype and specific clinical studies are rare. Here we present prospective data on characteristics, treatment and outcome of patients (pts) with advanced ILC in routine care in Germany. Methods The Tumor Registry Breast Cancer (TMK) has prospectively documented data of pts with breast cancer by oncologists in Germany since 2007. Since 2017 OPAL continues the TMK work with representation of all specialists (medical and gynecologic oncologists) treating advanced breast cancer (ABC). Both projects are prospective, observational, open, longitudinal multicenter cohort studies (clinical registries). Pts at the start of their treatment can be included after signing informed consent. Together over 7500 pts (4250 with ABC) will be recruited from over 150 sites in Germany. There is no treatment specification. Details on all (sequential) treatments, patient and tumor characteristics, clinical and patient-reported outcomes are documented. Follow-Up is until death or up to 5 years. Here, data as of March, 31st 2020 are presented. Results Pts with advanced ILC (n=372) were older at start of first-line treatment (median 68 vs. 63 years) while ECOG performance status (ECOG 0 25% vs 29%) and Charlson Comorbidity Index (CCI 0: 82% vs 84%) were similar compared to pts with IDC (n=1745). The lobular tumor was more often hormone receptor (HR) positive (87% vs 74%) and less often HER2 positive (14% vs 27%). The percentage of primary metastatic disease (M1) was 34% in both groups, while grade at diagnosis was more frequently G1/2 in the ILC group (73% vs 51%). The metastatic pattern was more often non-visceral only for the ILC group (26% vs 19%), and metastases were found more often in bone (52% vs 42%) and peritoneum (9% vs 2%) and less often in liver (20% vs 25%) and lung (7% vs 25%). Overall, pts with ILC were treated more often with endocrine therapy (ET) +/- CDK4/6-inhibitors (CDK4/6i) than pts with IDC (52% vs 33%), yet, ILC is more often HR-positive than IDC. Of pts receiving chemotherapy (CT) 53% of ILC and 56% of IDC tumors were treated with taxanes as first-line treatment. 20% of ILC vs. 24% of IDC tumors received a combination-CT. First-line treatment strategy was analyzed for the HR-positive, HER2-negative subgroup. From 2007-16 pts with ILC received more often ET (ILC (n=162) 54% vs IDC (n=696) 44%), while IDC were more often treated with CT first-line. Since approval of CDK4/6i, distribution of treatment strategies has been quite similar (ILC (n=123): CDK4/6i: 76%, ET: 15%, CT: 10% and IDC (n=311): CDK4/6i: 72%, ET: 12%, CT: 15%). Overall survival (OS) from start of first-line treatment was estimated for all pts recruited by 2016 (follow-up of at least 3 years). Median OS was comparable: ILC (n=224) 30.6 months (68% events, 95%-CI 26.1 - 36.9 months) and IDC (n=1217) 34.1 months (60% events, 95%-CI 30.6 - 38.4 months). For the HR-positive, HER2-negative subgroup, OS was also similar. A multivariate regression analysis on factors affecting OS will be presented. Conclusion Registries, like TMK/OPAL, can provide data on rare tumor subtypes. We show that ABC with an invasive lobular histology differs in receptor status (more often HR-positive) and metastatic pattern (e.g. more often non-visceral) from the invasive ductal subtype. Nevertheless, treatment strategies for first-line treatment are similar and median OS is comparable despite ILC pts being markedly older. Future research should focus on identifying pts who could benefit from personalized treatment approaches including tumor subtype as a factor to consider. Citation Format: Marc Thill, Mark-Oliver Zahn, Anja Welt, Elmar Stickeler, Arnd Nusch, Thomas Fietz, Jacqueline Rauh, Natalie Wetzel, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Nadia Harbeck, Achim Wöckel, Thomas Decker, OPAL study group. Rare patients in routine care: Treatment and outcome in advanced invasive lobular breast cancer in the prospective German research platform OPAL [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 PS11-16.

Introduction: Integration of patient preferences into shared decision making improves disease-related outcomes, but such data from patients with advanced breast cancer (aBC) are limited. The objective of this study was to demonstrate the relative importance of overall survival (OS) and progression-free survival (PFS) in relation to quality of life (QoL) and therapy-associated side effects from the perspective of patients with aBC. Methods: Postmenopausal patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative aBC receiving first- or second-line treatment were recruited throughout Germany. Patient-relevant attributes for aBC therapy assessment were collected using a stepwise multimodal approach. A conjoint matrix was developed, resulting in 2 attributes for therapy goals (OS and PFS), 4 for QoL, and 6 for side effects. An online quantitative survey was then performed using adaptive choice-based conjoint (ACBC) methodology. Results: The quantitative survey included 104 patients: 67 (64.4%) receiving first-line treatment and 37 (35.6%) receiving second-line treatment. The QoL attribute “physical agility and mobility” received the highest utility score (19.4 of 100%), reflecting the greatest importance to patients, followed by treatment goals (OS [15.2%] and PFS [14.4%]). Therapy-related side effects were less important, with nausea/vomiting being the most important (9.3%), followed by infection (6.4%) and hair loss (5.0%). The McFadden pseudo R2 (0.805), the root likelihood (0.864), and the χ2 test (2,809.041; p < 0.0001) indicated a very good fit of the statistical model. Conclusion: Using ACBC analysis, it appears that QoL, OS, and PFS are most important to postmenopausal patients with aBC in relation to cancer treatment. Side effects seem to be less important if OS or PFS are prolonged and the QoL is maintained. Thus, QoL, OS, and PFS should be considered equally when making treatment decisions in aBC.

Current evidence from the COVID-19 pandemic suggests that neonatal SARS-coronavirus-2 infections usually have a mild course. Data on how maternal infection during pregnancy affects fetal development are scarce. We present the unique case of a moderate preterm infant with intracranial bleeding and periventricular leukomalacia as a potential consequence of post-COVID-19 hyperinflammation during pregnancy.

Purpose The reliable detection of tumor-infiltrated axillary lymph nodes for breast cancer [BC] patients plays a decisive role in further therapy. We aimed to find out whether cross-sectional imaging techniques could improve sensitivity for pretherapeutic axillary staging in nodal-positive BC patients compared to conventional imaging such as mammography and sonography. Methods Data for breast cancer patients with tumor-infiltrated axillary lymph nodes having received surgery between 2014 and 2020 were included in this study. All examinations (sonography, mammography, computed tomography [CT] and magnetic resonance imaging [MRI]) were interpreted by board-certified specialists in radiology. The sensitivity of different imaging modalities was calculated, and binary logistic regression analyses were performed to detect variables influencing the detection of positive lymph nodes. Results All included 382 breast cancer patients had received conventional imaging, while 52.61% of the patients had received cross-sectional imaging. The sensitivity of the combination of all imaging modalities was 68.89%. The combination of MRI and CT showed 63.83% and the combination of sonography and mammography showed 36.11% sensitivity. Conclusion We could demonstrate that cross-sectional imaging can improve the sensitivity of the detection of tumor-infiltrated axillary lymph nodes in breast cancer patients. Only the safe detection of these lymph nodes at the time of diagnosis enables the evaluation of the response to neoadjuvant therapy, thereby allowing access to prognosis and improving new post-neoadjuvant therapies.

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.

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.

Was ist neu? Vorsorge, Früherkennung und familiärer Brustkrebs Mit dem Mammografie-Screening für Frauen ab dem 50. Lebensjahr steht in Deutschland eine etablierte Früherkennungsmaßnahme zur Verfügung. Eine Reduktion der Mortalität ist gesichert. Das Screening kann mittlerweile auch bei Frauen über 70 fortgeführt werden. Durch intensive Forschung im Bereich des familiären Mammakarzinoms kann das Hochrisikopatientenkollektiv präziser bestimmt und einer intensivierten Früherkennung zugeführt werden. Therapie lokal begrenzter Stadien – Senkung der Radikalität Die Behandlung erfolgt zielgerichtet und so wenig radikal wie möglich. Nach neoadjuvanter Chemotherapie kann immer öfter auf eine Brustamputation verzichtet werden. Die axilläre Lymphknotendissektion (ALND) bleibt wenigen Fällen vorbehalten. Die molekulare Subtypisierung ermöglicht individualisierte medikamentöse Therapien in der kurativen Absicht. Rekonstruktive Chirurgie Das BIA-ALCL stellt eine seltene Brustimplantat-assoziierte Erkrankung dar, bei der in den meisten Fällen eine Heilung möglich ist. Trotz steigender Inzidenz ist von Implantateinlagen nach adäquater Aufklärung der Patientin in Deutschland nicht abzuraten. Therapie des metastasierten Karzinoms Zur Behandlung des metastasierten Mammakarzinoms sollte wenn möglich eine gut verträgliche Therapie zur Erhaltung der Lebensqualität gewählt werden. Auch hier stehen immer mehr individualisierte Optionen zur Verfügung. Nachsorge Der Zeitraum der Nachsorge weitet sich aufgrund der Tumorbiologie auf 10 Jahre aus. Ausblick Eine ESR1-Mutation kann zukünftig möglicherweise als prädiktiver Marker hinsichtlich einer antihormonellen Therapie in der Metastasierung genutzt werden. Für eine PD-1-Blockade gibt es vielversprechende Ergebnisse in der neoadjuvanten Behandlung des triple-negativen Mammakarzinoms (TNBC).

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.

Background Parents and their children often disagree on the existence and severity of psychopathological symptoms, especially in major depressive disorder (MDD). Discrepant estimations pose a problem for the validity of diagnoses and illness severity with major implications for treatment evaluation. Methods 118 adolescents aged 13–18 years and their parents were interviewed and their reports were compared regarding the presence of a MDD diagnosis. In addition, severity ratings of depression symptoms reported in the Children's Depression Rating Scale-Revised (CDRS-R) were compared between parents and their offspring using multivariate analyses and polynomial regressions. The association between borderline features, functional impairment, and treatment history variables with parent-child agreement was assessed. Results In 38% of the cases, parents and adolescents agreed on DSM-IV diagnostic MDD criteria, while in 53%, only the adolescent endorsed criteria for a MDD. A MDD that was endorsed by parents and adolescents was characterized by higher depression severity, higher number of previous treatments, and higher functional impairment. Using a polynomial approach, neither age nor borderline tendencies were associated with agreement. Limitations We did not differentiate between mother's versus father's reports and borderline features were assessed by self-report only. Conclusions Adolescents and their parents gave differing reports of the existence and severity of depressive symptoms. The high discrepancy levels combined with the uncertainty of previously published findings due to methodological challenges are concerning. Clinicians and researchers need to consider discrepancies in agreement in relation to diagnosis and illness severity in the context of their clinical and research decisions.

Die Prognose von Patientinnen mit einem Mammakarzinom hat sich durch multimodale moderne Therapieverfahren in den letzten Jahren zunehmend verbessert. Immer mehr Frauen werden zu Langzeituberlebenden, Brustkrebs wird zu einer chronischen Erkrankung. Als Folge der Therapien kommt es jedoch bei einem Teil der Patientinnen zu dauerhaften Beeintrachtigungen oder Spatschaden. Es kann sich um korperliche Einschrankungen, psychische Beeintrachtigungen oder Probleme im sozialen Umfeld handeln, die sich negativ auf die Lebensqualitat auswirken. Durch die gestiegene Lebenserwartung werden immer mehr altere Langzeituberlebende betreut, die Komorbiditaten aufweisen. Ziel des Beitrags ist es, auf ausgewahlte Folgen und Nebenwirkungen der Therapie einzugehen und Masnahmen aufzuzeigen, wie diese reduziert werden konnen. Empfehlungen aus den aktuellen Leitlinien fliesen mit ein. Betroffenen steht grundsatzlich eine Vielzahl an Unterstutzungsmoglichkeiten zur Verfugung. Verschiedene Berufsgruppen sind in die Betreuung eingebunden. Um Langzeituberlebende dauerhaft gut betreuen zu konnen, mussen in Deutschland bestehende Strukturen optimiert werden. Haufig findet eine intensive Betreuung im Rahmen der Diagnosestellung und Akutbehandlung statt. Im Verlauf fehlen oft die Ansprechpartner der einzelnen Bereiche. Den Frauen sollte auch nach der Therapiephase eine multidisziplinare Betreuung zu Verfugung stehen. Langzeitnebenwirkungen und Spatschaden sollten moglichst fruh erkannt werden. Ferner sollte regelmasig das Vorliegen von psychischen Problemen oder Konflikten im sozialen Umfeld gepruft werden, um ggf. zeitnah zu intervenieren.

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.

Objective: This study aimed to identify patient preferences in aBC related to cancer treatment characteristics, i.e. to determine the relevance of gained lifetime (OS) and time to progression (PFS) in relation to quality of life (QoL) and therapy-associated side effects. Methods: Post-menopausal women with HR+/HER2-aBC receiving 1st or 2nd line treatment were recruited throughout Germany. Patient relevant attributes to assess aBC therapies were collected in a stepwise multi-methodological approach, consisting of desk research, qualitative interviews with patients (n=12), caregivers (n=3) and aBC treating physicians (n=2) and iterative reviews of the empirical findings in a cross-functional team. A draft conjoint matrix was developed which was refined by means of two pre-tests with aBC patients (n=9). The final conjoint matrix consisted of two attributes for therapy goals (OS and PFS), four for QoL and six for side effects. It represented the basis of the subsequent quantitative survey using adaptive choice-based conjoint methodology. Results: In the qualitative phase, QoL emerged as a multidimensional concept, consisting of several factors such as ability to lead a ‘normal’ life, physical capability to do things like before, mobility, carefreeness (not continuously be reminded of the disease), having goals and being able to go for them, and spend quality time with family and friends. Factors limiting QoL were symptom burden, medical controls and side effects, which were considered particularly disturbing if long-lasting, affecting everyday life and when effective management was not available. The quantitative sample consisted of 104 patients (67% 50-64 yrs/33% >65 yrs). Time from aBC diagnosis to survey participation was ≤5 years and >5 years in 50% of patients each. At the time of the survey, 67 patients (64.4%) were receiving 1st line and 37 (35.6%) 2nd line treatment, i.e. regular oral intake in 80%, regular injections in 29% and regular infusions in 15% of patients; the start of the current treatment was ≤1 year in 43% and >1 year in 57% of patients. QoL parameters (physical mobility and flexibility) received the highest value (19.4%), followed by treatment goals (OS 15.2%, PFS 14.4%). Therapy-related side effects turned out to be less important overall with nausea/vomiting being the most relevant side effect (9.3%), followed by infection risk (6.4%), diarrhea (2.9%) and mucosal dryness (1.2%). No significant differences were found between 1st and 2nd line patients. A relation between having experienced a side effect in the past and a desire to avoid it was identified for nausea, vomiting, and dry mucosa. There was no relation between the desire to avoid a side effect and its severity in the past. McFadden pseudo R2 (0.805), Root-Likelihood (0.864) and Chi-square test (2809.041, highly significant (p Citation Format: Mattea Reinisch, Norbert Marschner, Thorsten Otto, Agnieszka Korfel, Clemens Stoffregen, Achim Wöckel. Patient preferences: Results of a German adaptive choice-based conjoint analysis study in patients on palliative treatment for advanced breast cancer (aBC) [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 P1-17-08.

Introduction Tumor Registries give insight into routine treatment and complement the knowledge derived from randomized controlled trials (RCT), since characteristics of patients from RCTs often differ from those of patients in routine care. Furthermore, follow-up of patients in registries is generally longer which gives the possibility to analyze sequential treatments. Since 2007 the Tumor Registry Breast Cancer (TMK, NCT01351584) has prospectively collected data on treatment and outcome of patients with breast cancer in Germany. Among other topics, insights into “real-world” treatment and outcome and long-term observation of quality of life have been published. Since 2017 the registry platform OPAL (NCT03417115) has extended the work of the TMK by recruiting patients with advanced breast cancer (ABC) from all specialties (medical and gynecologic oncologists). The main aims are to observe the impact of novel treatments on patient outcome, and to identify areas for improvement of quality of care. Methods OPAL started in December 2017. Patients are prospectively recruited at start of their first systemic treatment for ABC. Follow-up continues until death or up to 5 years. There is no treatment specification. Detailed information on all (sequential) treatments, patient and tumor characteristics, physician-reported factors regarding treatment decision making, biomarker testing, outcomes (e.g. best response, progression-free and overall survival) are collected in a web-based data capture system with implemented checks for completeness and plausibility. Data are monitored by data management and on-site. Patient-reported outcomes (PROs) are collected at start of treatment and every 3 months thereafter. Patients can also give informed consent for their tumor samples to be used in future translational research (virtual biobank). All patient data remain in Germany. Here, first combined data from the TMK and OPAL (database as of 01.04.2019) are presented. Results Since 2007, 5076 patients have been recruited. Patients with ABC (n=2105, 434 since the start of OPAL) have a median age of over 60 years at start of treatment; about 60% have comorbidities. For patients with hormone-receptor positive (HRpos)/HER2 negative (HER2neg) ABC, first-line treatment has changed over the years. From 2007-11 (n=458) 60% of patients started with chemotherapy, decreasing to 48% in 2012-16 (n=528) and to 23% in 2018-19 (n=170) with 58% of patients now being treated with CDK4/6-inhibitor. First-line of HER2pos ABC has also changed from 79% of patients receiving trastuzumab (TRA) between 2007-12 (n=268) to 78% of patients receiving dual-blockade with TRA/pertuzumab in 2018-19 (n=97) and 10% receiving TRA only. About 25% of patients treated with TRA in 2018-19 received a biosimilar. Median overall survival (OS) of patients with start of first-line therapy between 2007-16 is currently 15 months for triple-neg (74% events), 34 months for HRpos/HER2neg (59% events), 40 months for HER2pos (52% events); median OS has not yet been reached for patients in OPAL. Conclusions For patients with HRpos/HER2neg ABC, a shift towards more endocrine therapy in the first-line setting, and a quick implementation of CDK4/6-inhibitors after their approval can be observed. In patients with HER2pos ABC, integration of trastuzumab biosimilars into routine care has started. Prognosis for patients with triple-negative ABC remains poor and new treatment options are urgently needed. OPAL together with TMK will allow to follow changes in treatment of patients with ABC in a “real world” setting in Germany, the application of sequential treatments, and their impact on clinical as well as patient-reported outcome. Citation Format: Elmar Stickeler, Nadia Harbeck, Marc Thill, Arnd Nusch, Marco Chiabudini, Lisa Kruggel, Martina Jänicke, Norbert Marschner, Mark-Oliver Zahn, Anja Welt, Achim Wöckel, Thomas Decker, OPAL Study Group. Therapy of advanced breast cancer for patients with hormone receptor-positive/HER2-negative and HER2-positive tumors is changing in real life: First results from the prospective, national research platform OPAL for patients with advanced breast cancer in Germany [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 P2-17-01.

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.

Mit ca. 69.000 jahrlichen Neuerkrankungen in Deutschland ist das Mammakarzinom der haufigste maligne Tumor der Frau. Die Lebenszeitpravalenz liegt bei etwa 12%. Zu den wichtigsten Risikofaktoren zahlen endokrine Faktoren, Lebensalter und Pradisposition. Tastbefunde oder Hautveranderungen zeigen sich meist erst im fortgeschrittenen Stadium, deshalb beinhaltet die Fruherkennung neben der klinischen Untersuchung eine Mammografie (standardmasig ab 50 Jahren). Bei auffalligem Befund erfolgt eine histologische Abklarung. Mit der Diagnosestellung eines Mammakarzinoms folgen in definierten Situationen zum Ausschluss einer Fernmetastasierung die Staginguntersuchungen. Die Operation ist ein wichtiger Teilschritt der kurativen Therapie. Zusatzlich sollte die Behandlung eine Strahlentherapie (bei brusterhaltender OP, positivem Lymphknotenstatus etc.) sowie abhangig von der Tumorbiologie und dem individuellen Patientenrisiko eine Systemtherapie (Chemo-, Antikorper-, Antihormontherapie) beinhalten. Aufgrund der Heterogenitat der Tumorbiologie ergibt sich eine individuell auf die Patientin ausgerichtete Therapie.

Background/Objectives: BRCA mutation carriers and women at high risk of breast/ovarian cancer are faced with the intricate question to opt for prophylactic surgeries and/or a periodic screening. The aim of this study was therefore to identify objective and emotional factors that have an impact on the decision-making process. Methods: Ninety-five women with BRCA mutations or women at increased breast/ovarian cancer lifetime risk were counseled at our outpatient department and either opted for prophylactic surgery or periodic screening. To identify the psychological factors that could have influenced the decision-making, a standardized questionnaire was applied. Additionally, clinical data were collected and were reviewed by a personal talk. Results: Seventy-one of the patients opted for an increased surveillance only, 21 for prophylactic surgeries. Positive predictors for prophylactic surgeries were sociodemographic characteristics such as parity and objective variables such as verified mutation status. Hierarchical regression analysis revealed that the need for safety in health issues has been the only significant psychological predictor of surgery beyond the objective factors. Fear of surgical procedures, menopausal symptoms after surgery, loss of attractiveness, or fear of interferences with sexual life did not significantly affect decision-making. Conclusion: Decision-making towards prophylactic surgeries is influenced by objective but also emotional factors. Knowing that fear and anxiety also have an important impact on decision-making, distinct counselling about the procedures, the subsequent risk reduction as well as the psychological effects of prophylactic surgeries are essential.

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.

Zur Vermeidung von Unter- oder Ubertherapien beim Mammakarzinom haben masgeblich die Leitlinienarbeit und das Zertifizierungssystem der Deutschen Krebsgesellschaft fur Brustzentren beigetragen. Am Beispiel von aktuellen operativen, medikamentosen und radioonkologischen Therapieansatzen wird diskutiert, wie risikoadaptiert eine Reduktion der Therapieaggressivitat und damit das Risiko fur Nebenwirkungen fur die Patientinnen erreicht werden konnte, ohne die inzwischen vielversprechenden Therapieergebnisse zu kompromittieren. Der Kreislauf aus wissenschaftlicher Evidenz, Erstellung von Leitlinien, Erarbeitung von Qualitatsindikatoren und Generierung von Wissen aus der Versorgung konnte erfolgreich zum Wohle der Patientinnen geschlossen werden.

Objective This study examined the role of the RAS in human breast cancer cells to question if there are differences between HR-positive and HR-negative cells with regard to regulation of VEGF. Methods Expression of different RAS components in hormone receptor (HR)-positive and HR-negative breast cancer cells was investigated using RT-PCR. Different stimulation protocols with different RAS inhibitors were used to investigate the effect on VEGF expression. Angiotensin II-dependent expression of VEGF was quantified by real time PCR. In addition, the effect of intrinsic RAS was studied performing siRNA knockdown of angiotensinogen (AGT). Statistical analysis were calculated using IBM SPSS Statistics Version 21. Results Expression of AT1R, AT2R, AGT and ACE was shown in HR-positive and HR-negative breast cancer cell lines. Extrinsic stimulation with angiotensin II increased VEGF significantly. After treatment with captopril or AT1R-inhibitor candesartan, VEGF-expression decreased significantly in HR-positive and HR-negative cell lines. However, inhibition of AT2R using PD 123,319 did not show any significant changes of VEGF. After prevention of intrinsic angiotensin II, extrinsic angiotensin II as well as the combination with inhibitors of the receptors caused a significant reduction of VEGF. Surprisingly, the overall effect of the RAS after knockdown of AGT revealed a significant increase of VEGF in HR-positive cells at any time while a significant decrease was observed in HR-negative cells after 144 hours incubation. Conclusion The RAS-dependent regulation of VEGF between HR-positive and HR-negative breast cancer cells seems do be different. These findings provide evidence for a possible future therapeutic strategy.

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.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

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.

Background This study examined the association between cognitive impairment and guideline adherence for application of chemotherapy in older patients with breast cancer. Patients and methods In the prospective multicenter cohort study BRENDA II, patients aged ≥65 years with primary breast cancer were sampled over a period of 4 years (2009-2012). A multiprofessional team (tumor board) discussed recommendation for adjuvant chemotherapy according to the German S3 guideline. Cognitive impairment was screened by the clock-drawing test (CDT) prior to adjuvant treatment. Results Two hundred and sixty-three patients were included in the study and CDT data were available for 193 patients. Thirty-one percent of the patients had cognitive impairment with different degree of severity. In high-risk patients (n = 61) tumor board recommendation in favor of chemotherapy was 90% and in intermediate-risk patients (n = 170) 27%. Not receiving recommendation for chemotherapy in spite of guideline recommendation was more frequent in patients with cognitive impairment (67%) vs patients without cognitive impairment (46%) with P = 0.02 (OR 2.4, 95% confidence interval (CI) 1.2-4.9). Age, education, migration background and comorbidities were not associated with chemotherapy recommendation by the tumor board among cognitively impaired patients. Once the tumor board had recommended chemotherapy, application of chemotherapy was similar in both groups of patients with or without cognitive impairment. Conclusion Almost one third of older patients with breast cancer are affected by cognitive impairment prior to adjuvant treatment. In these patients, cognitive impairment was associated with tumor board decision against chemotherapy in spite of a positive guideline recommendation.

Targeting of tumor immune escape mechanisms holds enormous therapeutic potential. Still, most patients progress under immune checkpoint blockade and some even become hyperprogressors. To investigate how cancer cells respond to activated but ineffective T cells, we challenged peptide-loaded MCF-7 breast cancer cells with antigen-specific CD8+ T cells in which lytic granules had been destroyed by pretreatment with Concanamycin A. Gene expression analysis after coculture revealed simultaneous induction of PD-L1, IDO1, CEACAM1, and further immunoregulatory checkpoints in breast cancer cells. Strikingly, we further observed gene signatures characteristic for dedifferentiation and acquisition of pluripotency markers including Yamanaka factors. Cognate interaction with nonlytic CD8+ T cells also increased the proportion of stem cell–like cancer cells in a cell-to-cell contact- or (at least) proximity-dependent manner in various cell lines and in primary breast cancer cell cultures; this induction of stem cell–like properties was confirmed by enhanced tumor-forming capacity in immunodeficient mice. Resulting tumors were characterized by enhanced cell density, higher proliferation rates, and increased propensity for lymphoid metastasis. These findings describe a widely underappreciated pathway for immune escape, namely immune-mediated dedifferentiation of breast cancer cells, which is associated with profound changes in gene expression and cellular behavior. As the enhanced malignant potential of cancer cells after nonlytic cognate interactions with CD8+ T cells enables increased tumor growth and metastasis in BALB/cnu/nu mice, the described mechanism may provide a possible explanation for the clinical phenomenon of hyperprogression in response to unsuccessful immunotherapy. Significance: This study shows that ineffective immune responses not only fail to clear a malignancy, but can also activate pathways in cancer cells that promote stemness and tumor-seeding capacity.

The relevant content changes for pathologists in the updated interdisciplinary S3 guideline "Early detection, diagnosis, therapy and aftercare of breast cancer" are explained and discussed in the context of the most recent evidence. These include recommendations for risk assessment using Ki-67 and the use of multigene tests in the decision for or against adjuvant chemotherapy in estrogen receptor(ER)‑/progesterone receptor(PR)-positive and human epidermal growth factor receptor 2 (HER2)-negative invasive breast cancer. In addition, the assessment of HER2 status is explained. It is described which threshold distance or resection margin status is considered sufficient for resection of ductal carcinoma in situ (DCIS) and invasive breast carcinoma. Finally, recommendations concerning the clinical consequences to be drawn from the detection of a risk lesion in a core needle or vacuum biopsy or at the resection margin of a breast surgical specimen are discussed.

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.

FATWO (female adnexal tumour of probable Wolffian origin) denotes a rare tumour of the female adnexa which has been described in nearly 80 cases worldwide and which presumably originates in the remains of the Wolffian ducts. In 10 to 20 percent of patients, a metastasis or recurrence was seen subsequently and for this reason, a malignant potential is attributed to the FATWO. Because of the small number of cases, there is no clear therapeutic recommendation. The method of choice currently is surgical treatment with hysterectomy and adnexectomy. The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. This work provides an overview of the literature on epidemiology, imaging and histopathological diagnostic features as well as therapeutic options of this same tumour form.FATWO (female adnexal tumour of propable Wolffian origin) bezeichnet einen seltenen Tumor der weiblichen Adnexe, der weltweit in knapp 80 Fällen beschrieben wurde und dessen Ursprung vermutlich in den Residuen der Wolffʼschen Gänge liegt. Bei 10 bis 20 Prozent der Patientinnen zeigte sich im Verlauf eine Metastasierung oder ein Rezidiv, weshalb dem FATWO ein malignes Potenzial zugeschrieben wird. Aufgrund der kleinen Fallzahl existiert keine klare Therapieempfehlung. Methode der Wahl ist derzeit eine operative Sanierung mit Hysterektomie und Adnexektomie. Der Nutzen von Radio- und Chemotherapien ist nicht eindeutig, vereinzelt wurden Therapieversuche mit Imatinib bei CD117-Positivität oder Therapieversuche auf endokriner Basis unternommen. Diese Arbeit zeigt eine Literaturübersicht über Epidemiologie, bildgebende und histopathologische Diagnosemerkmale sowie Therapieoptionen dieser seltenen Tumorform.

Among patients with breast or gynecological cancer, supportive care needs are both highly prevalent and enduring. However, little is known about whether meeting patients' needs is accompanied by increased quality of life (QoL). We aimed to explore patients' supportive care needs reported at the beginning of inpatient rehabilitation and examined whether meeting these needs resulted in improved QoL.In a multicenter, prospective cohort study with 2 measurement occasions (beginning and end of inpatient rehabilitation), 292 patients with breast and gynecological cancer (mean age 55 years; 71% breast cancer) were enrolled. In 73%, time since diagnosis was longer than 6 months. We obtained self-reports of supportive care needs in 12 domains and measured QoL using the EORTC QLQ-C30 functioning subscales.At the beginning of inpatient rehabilitation, top-ranking severe supportive care needs concerned coordination of care (48%), medical information (45%), alleviation of physical symptoms (42%) and support with improving health behaviors (36%). At the end of inpatient rehabilitation, all needs assessed declined significantly, although many patients still expressed strong needs in some domains. However, meeting patients' needs was accompanied by improvements in all functioning subscales.This is the first study to show that meeting breast and gynecological cancer patients' supportive care needs during inpatient rehabilitation resulted in improved QoL. Given the considerable proportions of patients still reporting unmet needs at the end of their stay, stronger and continuing efforts seem warranted to meet these needs and thus further increase QoL.

Drug loaded magnetic microspheres (MMS) can be magnetically guided to a target area within the body, where the pharmaceutical agent is released passively. For a faster release, the microspheres have to be disintegrated actively, e.g., by an increase of the temperature of the MMS. In the here presented study, poly(lactic-co-glycolic) acid (PLGA) microspheres were prepared. Magnetic nanoparticles with high magnetic heating performance and the drug camptothecin were embedded into the PLGA matrix. Resulting microspheres were characterized by means of dynamic light scattering, scanning electron microscopy, magnetometry, magnetic calorimetry, and UV/Vis spectrophotometry for determination of the drug release as a function of time and temperature. The MMS diameter is about 1.5 µm and the MMS show a content of magnetic material of up to 16 wt% and a drug loading of about 0.5 wt%. The MMS have a specific heating power of 161 W/gMMS, which enables sufficient magnetic heating for enforced drug release from the MMS in tissue concentrations of 2% by mass. Depending on the applied temperatures and the used PLGA type, the loaded drug is released within hours to days and a temperature increase from 37 to 43 °C leads to a significant faster drug release. The principle of magnetically triggered drug release is demonstrated by magnetic hyperthermia induced release of a drug from the MMS.

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.

Geburtshilfe und Frauenheilkunde 81(5), 526-538 (2021). doi:10.1055/a-1464-0953, Published by Thieme, Stuttgart

Background Pregnancy is an extraordinarily complex immunological process. For successful pregnancy maintenance the maternal immune system must adapt to and tolerate the semi-allogenic fetus at the fetomaternal interface of the placenta. This balance is regulated by cytokines with a predominant T helper 2 (Th-2) system and a suppressed inflammatory T helper 1 (Th-1) response. This study investigates the role of the Th-1 pro-inflammatory cytokine Interleukin-1 beta (IL-1β) and its role in early pregnancy loss. Patients and methods In order to identify differences in IL- β levels a TaqMan® Human Cytokine Network Array, with placental tissue obtained from patients with healthy pregnancies (n = 15) and recurrent miscarriage (n = 15), was carried out. Protein expression of IL-1β in the decidua of healthy pregnancies (n = 15), spontaneous (n = 18) and recurrent miscarriages (n = 15), was investigated by immunohistochemistry. The identification of IL-1β expressing cells in the decidua was done with double-immunofluorescence. Results Gene expression analysis identified a nearly 54-times higher expression of IL-1β in placental tissue of patients suffering from recurrent abortion. Immunohistochemistry confirmed a significant upregulation of IL-1β in the decidua of recurrent miscarriage specimens (p = 0.01) as well as in the decidua of women with spontaneous abortion (p = 0.001). Double-immunofluorescence identified decidual stoma cells as IL-1β expressing cells. Conclusion Significant upregulation of IL-1β may be associated with an imbalanced immune system and a procoagulant state that could be responsible for early pregnancy loss. These results provide new evidence of the complex interplay of IL-1β at the fetomaternal interface and its crucial role in miscarriage processes.

Geburtshilfe und Frauenheilkunde 81(4), 469-480 (2021). doi:10.1055/a-1397-7170, Published by Thieme, Stuttgart

Objective In this study, we investigated to which extent patients feel well informed about their disease and treatment, which areas they wish more or less information and which variables are associated with a need for information about the disease, medical tests and treatment. Methods In a German multi-centre prospective study, we enrolled 759 female breast cancer patients at the time of cancer diagnosis (baseline). Data on information were captured at 5 years after diagnosis with the European Organisation for Research and Treatment of Cancer (EORTC) Information Module (EORTC QLQ-INFO24). Good information predictors were analysed using linear regression models. Results There were 456 patients who participated at the 5-year follow-up. They reported to feel well informed about medical tests (mean score 78.5) and the disease itself (69.3) but relatively poorly about other services (44.3) and about different places of care (31.3). The survivors expressed a need for more information concerning: side effects and long-term consequences of therapy, more information in general, information about aftercare, prognosis, complementary medicine, disease and therapy. Patients with higher incomes were better informed about medical tests (β 0.26, p 0.04) and worse informed with increasing levels of fear of treatment (β − 0.11, p 0.02). Information about treatment was reported to be worse by survivors > 70 years old (β -0.34, p 0.03) and by immigrants (β -0.11, p 0.02). Survivors who had received additional written information felt better informed about disease, medical tests, treatment and other services (β 0.19/0.19/0.20/0.25; each p Conclusion Health care providers have to reconsider how and what kind of information they provide. Providing written information, in addition to oral information, may improve meeting those information needs.

Geburtshilfe und Frauenheilkunde 81(10), 1112-1120 (2021). doi:10.1055/a-1499-8431, Published by Thieme, Stuttgart

Purpose Electrosurgery is the gold-standard procedure for the treatment of cervical dysplasia. The quality of the outcome depends on the accuracy of performance, which underlines the role of adequate training of surgeons, especially, as this procedure is often performed by novice surgeons. According to our knowledge, medical simulation has up until now lacked a model, which focuses on realistically simulating the treatment of cervical dysplasia with the concerning anatomy. Methods and result In our work, we present a model created using 3D printing for holistically simulating diagnostic, as well as surgical interventions of the cervix, as realistically as possible. Conclusion This novel simulator is compared to an existing model and both are evaluated. By doing so, we aim to provide novice gynecologists with standardized and high-quality simulation models for practicing to improve their proficiency.