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Introduction Since 01/01/2020, the cervical cancer screening in Germany has been carried out due to the organized early cancer diagnosis guideline (oKFE-RL). In 2007, HPV vaccination was initiated in Germany. The main goal of both initiatives is to further reduce the incidence of invasive cervical cancer. To assess the effect of the new screening strategy in a timely manner, monitoring of short-term changes need to be considered. Ideally, the effects of both prevention methods would be presented together in one model. Materials and methods Because no change in the incidence of invasive cervical cancer is initially expected, the incidence of CIN 3 is used as a surrogate parameter to assess the effects of the prevention efforts. Based on expected additional effects of vaccination and co-testing, a model-based estimation of the expected CIN 3 incidence during the evaluation of the screening program is performed using the CIN 3 incidence in the Saarland population. Modeling results The oKFE-RL provides for two groups: Primary cytodiagnosis continues until 35 years of age. Here, in the next few years, CIN 3 incidence will be reduced not by the oKFE-RL but by the increasing proportion of vaccinated women. In the group over 35 years, co-testing was introduced with a stringent algorithm. Due to the higher sensitivity of the HPV test, significantly more CIN 3 are detected in the first round of 3 years and thus, the CIN 3 incidence initially increases. As these CIN 3 are absent in the second round, significantly fewer CIN 3 cases will be detected then. These effects suggest a global decrease in CIN 3 incidence of 25.8% after 6 years. Conclusion Observation of the age distribution curve of CIN 3 allows both effects of prevention to be assessed in a timely manner and separately. In the future, data from epidemiologic cancer registries should be incorporated into the model to replace modeling with real data.

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 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.

OBJECTIVE To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to prevent maternal-fetal transmission of cytomegalovirus (CMV) in women with primary first-trimester CMV infection. METHODS This was a prospective observational study of women with confirmed primary CMV infection in the first trimester who had the first HIG administration at or before 14 weeks' gestation. All women had biweekly HIG treatment until 20 weeks' gestation at a dose of 200 IU/kg of maternal body weight. Each subject underwent amniocentesis at least 6 weeks after first presentation at about 20 weeks. Primary outcome was maternal-fetal transmission at the time of amniocentesis, and secondary outcome was the frequency of congenital CMV infection at birth. The results were compared with a historic cohort of women with first-trimester CMV infection who did not undergo HIG treatment and who had amniocentesis at about 20 weeks. RESULTS Subjects were 40 pregnant women with a primary CMV infection, with a median gestational age at first presentation of 9.6 (range, 5.1-14.3) weeks. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks. Within this interval, HIG was administered between two and six times in each patient. While CMV immunoglobulin-G (IgG) monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV-IgG avidity indices remained stable over the whole treatment period. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5% (95% CI, 0-13.2%)). At delivery, two additional subjects were found to have had late-gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% (95% CI, 1.6-20.4%) in our 40 cases. All infected neonates were asymptomatic at birth. The matched historical control group consisted of 108 pregnancies. Thirty-eight transmissions (35.2% (95% CI, 26.2-45.0%)) occurred in the control group, which was significantly higher (P

[for full text, please go to the a.m. URL], GMS Journal for Medical Education; 37(4):Doc37

In Deutschland wurden seit 2003 als gemeinsame Initiative der Deutschen Krebsgesellschaft (DKG) und der Deutschen Gesellschaft fur Senologie (DGS) Brustkrebszentren etabliert. Die DKG hat dazu ein Zertifizierungssystem entwickelt, welches in Audits Prozess- und Behandlungsqualitat uberpruft. In der S3-Leitlinie zur „Fruherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms“ wurden Qualitatsindikatoren entwickelt. Sie werden von den zertifizierten Zentren in hohem Mase erfullt. Diesem Modell sind eine Reihe weiterer Organkrebszentren gefolgt. Durch die Einfuhrung des Krebsfruherkennungs- und Krebsregister-Gesetzes (KFRG) wird kunftig eine flachendeckende Einrichtung klinischer Krebsregister erfolgen. Zur Darstellung der Ergebnisqualitat ist eine Vernetzung zwischen Krebszentren und klinischen Krebsregistern erforderlich. Daruber hinaus bietet diese Vernetzung die Grundlage fur die Entwicklung qualitatsverbessernder Strategien.

Background: Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life.Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL). Methods: The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors. Results: In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 – 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences. Conclusions: We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL. Citation Format: Wallwiener M, Nabieva N, Haeberle L, Taran FA, Hartkopf AD, Volz B, Overkamp F, Brandl AL, Kolberg H-C, Hadji P, Tesch H, Ettl J, Lux MP, Lueftner D, Belleville E, Fasching PA, Janni W, Beckmann MW, Wimberger P, Hielscher C, Fehm T, Brucker SY, Wallwiener D, Schneeweiss A, Mueller V. Impact of disease progression on health-related quality of life in patients with metastatic breast cancer in the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-11-10.

Background For breast cancer patients with metastases which are not life threatening national and international guidelines recommend the exhaustion of all antihormonal therapeutic options before recommending chemotherapy. In Germany up to now only everolimus was an additional option to overcome endocrine resistance. CDK4/6 inhibitors recently became available in Germany (Nov 2011). Aim of this analysis was the identification of predictors for a decision against an antihormonal treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for metastatic breast cancer patients. Besides biomarker research the description of real-world treatment data was one of the main study aims. This analysis was restricted to first line metastatic patients who were hormone receptor (HR) positive and HER2 negative. First, predictors were identified with a multiple logistic regression model. Then patients, who received chemo or not ,were compared with regard to overall survival using Cox regression analysis with the predictors for chemotherapy from above and additionally chemo status (yes/no) Results A total of 389 HR-positive and HER2-negative patients with detailed treatment information were included during the 1st line therapy into PRAEGNANT. Of those 173 (44.5%) received a chemotherapy, 190 an antihormone therapy (AHT) (48.8%), and 26 (6.7%) everolimus+AHT. In the multiple logistic regression model, older patients, lower graded tumors, bone only disease and previous adjuvant chemotherapy were associated with a lower rate of first line chemotherapies. BMI and number of concomitant diseases had no influence on the choice of first line metastatic therapy. In patients with visceral metastases 58.1% were treated with a 1st line chemo, while in patients with brain metastases or bone only metastases these numbers were 55.6% and 26.9%. Grading had an influence with patients having a G1, G2 and G3 tumor receiving 1st line chemo in 28.0%, 38.4% and 63.2% of the cases respectively. Patients who received chemo seemed to have a worse overall survival than patients who did not receive chemo (adjusted HR 1.58; 95% CI, 0.89 to 2.18). However, this result was not signifcant (p = 0.12). Overall survival was primarily influenced by ECOG and location of metastasis Conclusion The usage of chemotherapy can be predicted with age, metastasis pattern, grading and previous use of chemotherapy. However, we could not show that patients benefited from chemotherapy. On contrary, there was a tendency that patients treated with chemotherapy had poorer overall survival. Further studies with larger sample sizes are needed to confirm this claim. Citation Format: Huober J, Fasching PA, Taran F-A, Volz B, Overkamp F, Kolberg HC, Hadji P, Tesch H, Haeberle L, Ettl J, Hartkopf AD, Lux MP, Lueftner D, Wallwiener M, Mueller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Fersis N, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Wallwiener D, Brucker SY, Schneeweiss A, Fehm TN. Factors associated with first line chemotherapy use in patients with hormone receptor positive, HER2 negative metastatic breast cancer – data from the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-07.

Background: Despite novel, targeted therapies, metastatic breast cancer patients have an extremely unfavourable prognosis. Prognostic and predictive factors for patients with advanced breast cancer are not well understood. Molecular assessment of the patient and the tumor in the metastatic situation is not routinely performed despite advances in molecular precision medicine indicating great benefit to this patient group. Here we present early findings from the first 142 patients of a prospective molecular breast cancer registry with completed transcriptomic profiling. Methods: The PRAEGNANT study proctocol (NCT02338767) is a molecular registry designed to provide an infrastructure for the real-time comprehensive analysis of tumor and patient molecular characteristics under study conditions. Formalin fixed paraffin embedded tumors have been used from this registry to identify molecular, transcriptomic predictors for overall survival (OS). Known clinical correlates for OS (e.g. hormone-receptor status, age at diagnosis, and BMI) were analyzed by Cox proportional hazard ratios, and compared to transcriptomic markers of outcomes. Transcriptomes for all patient tumors were sequenced on the Illumina sequencing platform, and analyzed by RSEM to estimate transcripts per million (TPM) values for each gene isoform. Log-TPM values were used in established (PAM50) and novel (hierarchical clustering) expression-based subtyping of tumor samples. Expression-based subtypes were demonstrated to be strong prognostic indicators by Cox analysis. A Lasso regression machine learning algorithm was used to develop an expression-based predictive model of OS. Results: Hormone receptor positivity (HR=0.7, p Conclusions: Here we demonstrate using molecular profiling to develop prognostic signatures that out-perform standard clinical correlates of poor outcomes, even in a small subset of the total cohort. As the PRAEGNANT cohort expands these prognostic tools will continue to improve and supplement physician knowledge to improve patient outcomes. Citation Format: Szeto C, Benz S, Nguyen A, Rübner M, Wallwiener D, Tesch H, Hadji P, Fehm TN, Janni W, Overkamp F, Lueftner D, Lux MP, Wallwiener M, Beckmann MW, Huebner H, Ettl J, Hartkopf AD, Mueller V, Taran FA, Belleville E, Schneeweiss A, Soon-Shiong P, Rabizadeh S, Fasching PA. Developing prognostic indicators of poor outcomes in PRAEGNANT metastatic breast cancer cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-20.

Background Breast Cancer registries can help to understand how patient groups are treated outside clinical trials and what outcome is to expected for specific patient groups and therapy lines, which are not included into clinical trials. Here we present overall survival data according to therapy lines, patient and tumor characteristics. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for 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 therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the comparison of overall survival data for different patient groups. For that analysis was restricted to patients included in the first therapy line for subgroup comparisons. Only for the analysis of the effect of therapy line on overall survival the complete dataset was used. Results A total of 1854 patients took part in this analysis. Of those 1016 were included first line, and 340, 213 and 285 patients 2nd line, 3rd lin4 and 4th line or higher respectively. A total of 339 deaths were observed. Two year survival rates (2Y-OS) for these groups were 75%, 65%, 57% and 36% (p(log-rank) Conclusion This breast registry included patients over all therapy lines however mainly during the 1st line of therapy. Simple patient and tumor characteristics can classify patients into patients with differently favourable prognosis. Patients with HER2 positive disease had the best overall survival, while TNBC and luminal B like patients had the worst prognosis. As most of the patients were luminal A like 43% of all deaths occured within the group of luminal A like patients, which will need further focus for therapy development in the future. Citation Format: Taran F-A, Fasching PA, Volz B, Huober J, Overkamp F, Kolberg HC, Hadji P, Tesch H, Haeberle L, Ettl J, Lux MP, Hartkopf AD, Lueftner D, Wallwiener M, Müller V, Beckmann MW, Belleville E, Wimberger P, Hielscher C, Geberth M, Fersis N, Abenhardt W, Kurbacher C, Wuerstlein R, Thomssen C, Untch M, Janni W, Fehm TN, Wallwiener D, Brucker SY, Schneeweiss A. Overall survival of metastatic breast cancer patients – data from the PRAEGNANT breast cancer registry [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-09.

Introduction As early breast cancer might relapse even after complete removal of breast and lymphnodes, the disease must persist in secondary sites. The detection of disseminated tumor cells (DTC) in the bone marrow (BM) has been described as a surrogate of residual disease. Various trials showed an impaired prognosis of DTC positive early breast cancer (EBC) patients. The PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) study is a large international pooled analysis that aimed to assess the prognostic impact of DTC detection in patients with EBC. Methods A pre-specified protocol was followed, and centers known to practice BM sampling for DTC detection were contacted for individual patient data. Patients with EBC, with available follow-up data and BM sampling before any anti-cancer treatment were eligible. BM aspirates were collected at the time of primary surgery. DTC were identified by antibody (A45-B/B3, AE1/AE3, 2E11 and E29) staining against cytokeratin. The DTC status was compared to other prognostic factors using the chi-squared test. Univariate log-rank test and multivariate cox regression were used to compare survival of DTC positive versus DTC negative patients. Results Individual data from 10,320 patients (11 centers from Europe and USA) were included with a median follow-up of 91 months. Of all patients, 2,823 (27.4 %) were DTC positive. DTC detection was associated with higher tumor grade, higher T stage, nodal positivity, ER and PR negativity, and HER2 positivity (all p Conclusions Detection of DTC in the bone marrow is an independent prognostic marker in patients with non-metastatic breast cancer. Further studies should investigate the impact of DTC on metastatic cancer progression and their role for clinical decision making. Citation Format: Hartkopf AD, Brucker SY, Taran F-A, Harbeck N, von Au A, Naume B, Pierga J-Y, Hoffmann O, Beckmann MW, Rydén L, Fehm T, Aft R, Montserrat S, Walter V, Rack B, Schuetz F, Borgen E, Ta M-H, Bittner A-K, Fasching P, Fernö M, Krawczyk N, Weilbaecher K, Margelí M, Hahn M, Jueckstock J, Domschke C, Bidard F-C, Kasimir-Bauer S, Schoenfisch B, Kurt AG, Wallwiener M, Gebauer G, Wallwiener D, Janni W, Pantel K. International pooled analysis of the prognostic impact of disseminated tumor cells from the bone marrow in early breast cancer: Results from the PADDY study [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 GS5-07.

In recent years, numerous new therapy options for patients with breast cancer have been developed in clinical studies, with some options already approved for routine treatment. As the speed at which innovations are introduced increases, the importance of conferences also increases, as conferences are where the data underpinning new therapies are usually presented for the first time. This review looks at publications of the ASCO (American Society of Clinical Oncology) and ESMO (European Society of Medical Oncology) conferences in 2017, summarizes them and evaluates them in the context of existing data. The focus is on new insights for neoadjuvant therapy and new treatment options in the metastatic setting, such as the use of CDK4/6 inhibitors or PARP inhibitors. The first results of treatments with checkpoint inhibitors are presented. With the patent expiry of trastuzumab, a number of study results for trastuzumab biosimilars have also been published. The digitization of patient care provides the first results on quality of life and prognosis of patients with advanced cancer. Digital communications between patients and physicians are being evaluated in several studies in Germany. As the discussion about patient-relevant endpoints for patients in the metastatic setting continues, overall survival rates from studies of big endocrine-based therapies are urgently needed. Preliminary analyses of small study cohorts offer initial insights. In the context of improving patient care, in the coming years, questions will center on which patients particularly benefit from certain therapies and which patients need particular protection from specific side effects. Questions about these predictors are raised in many scientific projects as attention increasingly focuses on this topic.In den letzten Jahren sind zahlreiche neue Therapieoptionen für die Patientin mit einem Mammakarzinom in klinischen Studien entwickelt worden und teilweise zur Zulassung gekommen. Bei zunehmender Geschwindigkeit neuer Innovationen nimmt die Bedeutung von Kongressen zu, auf denen meist zum ersten Mal Daten zu den entsprechenden Therapien präsentiert werden. Diese Übersichtsarbeit greift Veröffentlichungen der Kongresse ASCO (American Society of Clincial Oncology) und ESMO (European Society of Medical Oncology) aus dem Jahr 2017 auf und fasst sie im Kontext bestehender Daten zusammen. Der Fokus liegt auf Erkenntnissen aus der neoadjuvanten Situation und Neuigkeiten aus der metastasierten Situation, wie der Einsatz von CDK4/6-Inhibitoren oder PARP-Inhibitoren. Des Weiteren werden erste Ergebnisse zur Behandlung mit Checkpoint-Inhibitoren dargestellt. Bei baldigem Patentablauf von Trastuzumab sind zudem einige Studienergebnisse zu Trastuzumab-Biosimilars veröffentlicht worden. Auch die Digitalisierung der Patientenversorgung liefert erste Ergebnisse in Bezug auf Lebensqualität und Prognose von Patientinnen mit fortgeschrittener Krebserkrankung. Die digitale Kommunikation zwischen Patientin und Ärztin bzw. Arzt wird auch in Deutschland in einigen Studien untersucht. Bei anhaltender Diskussion über patientenrelevante Endpunkte für Patientinnen in der metastasierten Situation werden die Gesamtüberlebensdaten für die großen endokrin basierten Studien dringend erwartet. Erste Einblicke liefern vorläufige Analysen an kleinen Studienkollektiven. Im Rahmen der Patientenversorgung werden in den nächsten Jahren die Fragen aufkommen, welche Patientinnen besonders von bestimmten Therapien profitieren und welche vor besonders relevanten Nebenwirkungen geschützt werden können. Die Frage nach diesen Prädiktoren begleitet viele wissenschaftliche Projekte und bekommt eine besondere Aufmerksamkeit.

Vor Abschluss ihrer fertilen Phase erkranken in Deutschland etwa 9000 Frauen pro Jahr an einer onkologischen Erkrankung. Die gewahlte Chemotherapie kann die spatere Fruchtbarkeit masgeblich beeintrachtigen. Die Entnahme von Ovarialgewebe zur Kyrokonservierung und spateren Retransplantation hat als Therapieoption zum Fertilitatserhalt mittlerweile einen festen Stellenwert. So kann bei Verlust der Fertilitat durch eine Chemotherapie diese ggf. wiederhergestellt werden. Die erste autologe Ovarialgewebstransplantation am Menschen wurde 2000 von Oktay et al. beschrieben. Im Jahr 2004 berichteten dann Donnez et al. weltweit erstmalig von einer Geburt nach Ovarialgewebstransplantation, und 2012 kam es in Deutschland zur Geburt eines gesunden Kindes nach Ovarialgewebstransplantation. In Deutschland werden mittlerweile jahrlich weit uber 300 Ovarialgewebsentnahmen im Rahmen des Netzwerks „FertiPROTEKT“ durchgefuhrt. Seit der Erfassung der Daten im FertiPROTEKT-Register wurden somit etwa 2500 Kryokonservierungen durchgefuhrt. Das Netzwerk „FertiPROTEKT“ von Gynakologen und Biologen aus dem deutschsprachigen Raum wurde 2006 gegrundet. Es hat sich zur Aufgabe gestellt, Frauen vor einer potenziell ovarschadigenden Therapie bezuglich fertilitatserhaltender Techniken zu beraten. Mittlerweile wird uber Schwangerschaftsraten von bis zu uber 33 % und eine Geburtenrate von 25 % nach Ovarialgewebsretransplantation berichtet. Naturlich mussen die individuellen Risiken individuell mit der Patientin besprochen werden. Somit hat die noch vor wenigen Jahren als experimentell zu betrachtende Kryokonservierung und Retransplantation von Ovarialgewebe einen festen Stellenwert in der Fertilitatsprotektion erhalten.

Introduction Especially in oncology patients, Patient Reported Outcomes (PRO) play an increasingly important role to measure subjectively perceived health status and treatment effects. At the moment, paper-based surveys of PRO still predominate (pPRO); in recent years, data on patient-relevant endpoints is being increasingly collected electronically (ePRO). The aim of the study was to analyze the acceptance of an ePRO-survey tool in breast cancer patients within the PRAEGNANT multicenter trial. Furthermore, it should be considered, whether differences in response behavior between pPRO and ePRO can be identified (reliability check). Materials and Methods ePROCOM (Patient Reported Outcomes and Compliance Anaysis) was conceptualized as a monocenter, randomized, parallel-group, cross-over study. Female patients with diagnosis breast cancer aged more than 18 years were included.We randomized the patients into one of two study arms. In study arm A the patients are first asked to use the electronic, web-based tool to document the patient questionnaire (EORTC QLQ C-30 and FACT-B). Afterwards the patients were asked to fill and evaluate the paper-based questionnaires accordingly, followed by evaluation of usability, acceptance and capability. In study arm B the course varies by meaning that paper-based evaluation will be followed by the assessment of electronic data capture. Results N=110 patients with breast cancer in adjuvant or neoadjuvant situation completing the study during an outpatient visit at the University Hospitals in Tuebingen and the National Cancer Centre Heidelberg (average age: 52.4). In most patients, there were no differences in terms of acceptance between pPRO and ePRO. Only in some older patients with a lower quality of life hurdles for ePRO could be identified, because of lower acceptance rates. We could not find significant differences in response behavior between pPRO and ePRO. Discussion Because no differences in response behavior could be identified, the tool can be define as reliable possibility to measure patient reported outcomes. E-PRO surveys appear to be suitable for use in breast cancer patients. However, there is a need of support in older and more ill patients, to participate form the technical capabilities of ePRO. Citation Format: Wallwiener M, Simoes E, Hartkopf AD, Taran F-A, Keilmann L, Sickenberger N, Stevanovic S, Belleville E, Ladra C, Schneeweiss A, Wallwiener D, Brucker SY, Graf J. Reliability and acceptance of e-based survey instruments for measuring patient reported outcomes (PRO) in breast cancer patients: First results of the ePROCOM study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-11-05.

Introduction/Background The ovarian cancer represents the seventh most common cancer in women worldwide. An elevated serum CA 125 level in association with a pelvic mass, pleural effusion, and massive ascites usually signifies a dismal prognosis in a postmenopausal woman. Meigs’ syndrome consists of a benign ovarian tumor accompanied by ascites and pleural effusion. Methodology Surgery and histopathological examination are required for the correct diagnosis and treatment. The patient underwent a laparotomy with bilateral salpingo-oophorectomy. All cases of Meigs’ syndrome with elevated CA 125 that have been reported were included at this review. Results Meigs’ syndrome with marked elevated CA 125 is a rare clinical entity and only 47 cases have been reported. An elevated CA 125 level can be falsely positive for ovarian malignancy because the quantity of ascites might be correlated with a rise in the level of CA 125. Conclusion Postmenopausal women with a pelvic mass, pleural effusion, ascites and elevated serum CA 125 levels probably suffer from malignant ovarian tumors. However, it is important to remember that these findings does not always predict a lethal condition, but a benign adnexal lesion as part of Meigs’ syndrome, should be also considered as an unusual but existing diagnostic possibility. Disclosure Nothing to disclose.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Kuster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation.

Die Gesellschaft ist im Wandel, so auch ihr Einfluss auf die Gesundheit der Frau und das Fachgebiet Frauenheilkunde. Dies beinhaltet kontinuierliche Herausforderungen und die Frage, wie ihnen begegnet werden soll. Eine Starken-Schwachen-Analyse des Fachgebiets zeigt neben Problemfeldern auch Chancen. Eine solche stellt Frauengesundheit als Perspektive dar. Sie eint das Fachgebiet in einer weitreichenden, ganzheitlich ausgerichteten Aufgabe, getragen von der Innovationskraft seiner zahlreichen (Sub-)Disziplinen. Der ganzheitliche Aspekt kommt in einer besonderen Weise in allen Bestrebungen zur Personalisierung von Diagnostik, Therapie, aber beispielsweise auch geschlechtsspezifischen Kommunikationsstrukturen zum Ausdruck, den derzeitigen Wandel in der Medizin gleichzeitig spiegelnd und bahnend. In der Gestaltung eines tragfahigen Rahmens fur das verantwortungsvolle Handeln in allen Teilbereichen des Fachs, der Freiraume erhalt und die finanzielle Basis starkt, besteht eine zentrale Aufgabe – nicht zuletzt durch das Mitwirken in Gremien und der gesundheitspolitischen Diskussion. Dies gilt insbesondere mit Blick auf die Aufgabe einer nachhaltigen Pravention, fur die das Fach, das alle Lebensphasen der Frau erreicht, ebenso pradestiniert ist wie durch seine Innovationen, die ganzlich neue Moglichkeiten eroffnen. Durch strukturelle Impulse unterstutzt das Fachgebiet die Einheit in der Vielfalt: modular definierte und abgestimmte Strukturen, unterstutzt von Departmenten fur Frauengesundheit, konnen den zahlreichen Anforderung und der gesellschaftlich geforderten Flexibilitat am ehesten entsprechen und alle Teilgebiete fur eine gemeinsame Zukunft verankern.

Operationen verursachen Komplikationen. Das Auftreten von Komplikationen lasst sich reduzieren, aber niemals ganz vermeiden. Vor diesem Hintergrund ist es notwendig, die pathophysiologischen Zusammenhange von Komplikationen zu kennen und Vermeidungsstrategien zu erlernen. Der Beitrag zeigt eine Ubersicht uber die Risikofaktoren fur Komplikationen. Diese Ubersicht hat das Ziel, dass Operateure Hochrisikosituationen zu umgehen lernen. Des Weiteren wird auf spezielle Komplikationen bei Brustoperationen eingegangen und Fehlerquellen werden aufgezeigt. Dabei soll der Leser ein Bewusstsein fur diese Fehlerquellen entwickeln, um selbst solche Situationen vermeiden zu konnen.

To examine the efficacy of biweekly hyperimmunoglobulin (HIG) administration to prevent maternal-fetal transmission of cytomegalovirus (CMV) in women with primary first-trimester CMV infection.This was a prospective observational study of women with confirmed primary CMV infection in the first trimester who had the first HIG administration at or before 14 weeks' gestation. All women had biweekly HIG treatment until 20 weeks' gestation at a dose of 200 IU/kg of maternal body weight. Each subject underwent amniocentesis at least 6 weeks after first presentation at about 20 weeks. Primary outcome was maternal-fetal transmission at the time of amniocentesis, and secondary outcome was the frequency of congenital CMV infection at birth. The results were compared with a historic cohort of women with first-trimester CMV infection who did not undergo HIG treatment and who had amniocentesis at about 20 weeks.Subjects were 40 pregnant women with a primary CMV infection, with a median gestational age at first presentation of 9.6 (range, 5.1-14.3) weeks. On average, HIG administration started at 11.1 weeks and continued until 16.6 weeks. Within this interval, HIG was administered between two and six times in each patient. While CMV immunoglobulin-G (IgG) monitoring showed periodic fluctuations during biweekly HIG administration cycles, high CMV-IgG avidity indices remained stable over the whole treatment period. Maternal-fetal transmission before amniocentesis occurred in only one of the 40 cases (2.5% (95% CI, 0-13.2%)). At delivery, two additional subjects were found to have had late-gestation transmission. Considering all three cases with maternal-fetal transmission, the transmission rate was 7.5% (95% CI, 1.6-20.4%) in our 40 cases. All infected neonates were asymptomatic at birth. The matched historical control group consisted of 108 pregnancies. Thirty-eight transmissions (35.2% (95% CI, 26.2-45.0%)) occurred in the control group, which was significantly higher (P 0.0001) than the transmission rate in the HIG treatment group.After a primary maternal CMV infection in the first trimester, biweekly HIG administration at a dose of 200 IU/kg prevents maternal-fetal transmission up to 20 weeks' gestation. Copyright © 2018 ISUOG. Published by John WileySons Ltd.

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition.

Genitale Aplasien gehen mit erheblichen Einschrankungen der Lebensqualitat einher. International besteht kein Konsens uber die optimale Therapie. Darstellung und Bewertung der unterschiedlichen Therapieoptionen am Beispiel der Vaginal- und Zervixaplasie. Auswertung einer aktuellen Literaturrecherche unter Berucksichtigung eigener Erfahrungen. Unserer Meinung nach kann die laparoskopisch assistierte Anlage einer Neovagina als operative Therapie der ersten Wahl angesehen werden, fur die Zervixaplasie gibt es keinen entsprechenden Konsens. Studien mit hoheren Fallzahlen und standardisierter Nachbeobachtung sowie mehr randomisierte, kontrollierte Studien waren wunschenswert.

In den letzten Jahrzehnten sind zwar Fortschritte in der Behandlung des metastasierten Mammakarzinoms erzielt worden, jedoch orientieren sich nur wenige Therapien an den individuellen Eigenschaften der Patientin oder der Tumorerkrankung. Mehr als 10 Jahre nach der Veroffentlichung der menschlichen genetischen Sequenz haben sich die Analysemethoden dahingehend verbessert, dass grose Hoffnung besteht, die Therapie weiterzuentwickeln und im Sinne einer „Prazisionsmedizin“ individuell fur die Patientin und die Tumorerkrankung zu gestalten. Hierbei werden Biomarker auf jeder Ebene der Systembiologie herangezogen (Genetik, Epigenetik, Genexpression, micro-RNA, Proteomics und weitere). Diese Individualisierung hat zu einer neuen Generation von Studien gefuhrt, sodass manche Arzneimittelentwicklungen nur noch fur sehr kleine Patientinnen-Subgruppen durchgefuhrt werden. Die Organisation der Erfassung von Patientinnen und molekularen Tumordaten ist deswegen von besonderer Bedeutung fur die erfolgreiche Durchfuhrung von klinischen Studien. Diese neue Form der Medizin stellt eine besondere Herausforderung fur Patientinnen und Arzte dar. Der Erhalt der Lebensqualitat sollte auch in diesem neuen Zeitalter der Medizin als zentrales Therapieziel im Fokus stehen. In diesem Ubersichtsartikel werden wir die Entwicklungen der letzten Jahre aufzeigen und das PRAEGNANT-Studiennetzwerk vorstellen, welches die oben genannten Probleme und Ziele angeht und eine professionalisierte Infrastruktur hierfur aufbaut.

Einleitung: Die EvaluateTM-Studie (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor positive breast cancer patients receiving letrozole treatment) ist eine prospektive, nicht interventionelle Studie, die das Therapiemanagement und die Compliance im Rahmen der Routineversorgung unter einer Therapie mit Letrozol bei postmenopausalen Patientinnen mit einem invasiven, hormonrezeptorpositiven Mammakarzinom als Studienziel hatte. In dieser Publikation werden die Parameter bei Studieneinschluss berichtet. Material und Methoden: Von Januar 2008 bis Dezember 2009 wurden insges. 5045 Patientinnen in 310 Prufzentren in die EvaluateTM-Studie eingeschlossen. Zugelassen waren Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom in der adjuvanten und metastasierten Therapiesituation. 373 Patientinnen mussten aus unterschiedlichen Grunden aus den Analysen ausgeschlossen werden. Ergebnisse: Insgesamt wurden 4420 Patientinnen in der adjuvanten und 252 Patientinnen in der palliativen (metastasierten) Situation in die Studie eingeschlossen. Bei 4181 Patientinnen in der adjuvanten Situation wurde direkt nach operativer Therapie mit einer Aromataseinhibitortherapie mit Letrozol begonnen (upfront). Bei 200 Patientinnen wurde zunachst Tamoxifen gegeben und in den Jahren 2 – 5 nach Diagnosestellung mit der Aromatasehemmertherapie mit Letrozol begonnen (switch), und bei 39 Patientinnen erst 6 – 10 Jahren nach Diagnosestellung (extended endocrine therapy). Die Patientinnen- und Tumorcharakteristika lagen ebenso wie die Begleiterkrankungen und die Begleitmedikation im Bereich des Erwarteten. Schlussfolgerung: Die Daten der EvaluateTM-Studie werden einen guten Einblick in das Therapiemanagement von postmenopausalen Patientinnen mit einem hormonrezeptorpositiven Mammakarzinom im Rahmen der Routineversorgung geben. Geplante Analysen beinhalten die Therapiepersistenz und die Zufriedenheit mit den Informationsstrukturen und dem Aufklarungsinhalt.

PURPOSE To delineate the relevance of pelvic and para-aortic node involvement in optimally cytoreduced (residual tumour 0-≤ 0.5) >0 and ≤ 50 % of affected nodes; (3) (>0.5-≤ 1) >50 % of affected nodes. Clinical parameters were retrospectively evaluated. Kaplan-Meier survival curve was used to evaluate the prognostic value. RESULTS Most often serous histology, histologic grade 3 and a node ratio >0-≤ 0.5 (61.1 %) were detected. Complete cytoreduction (R = 0 mm) has significant best prognostic impact compared to R > 0 mm-1 cm (OS: p = 0.047, PFS: p = 0.00). Node involvement was associated with serous histology and grade 3. Increasing node ratio leads to significant decreased OS (p = 0.019) and significant best OS was associated with node ratio >0-≤0.5. CONCLUSIONS The goal is optimal cytoreduction in advanced ovarian cancer. More extensive lymphadenectomy seems to play an important role in providing an accurate staging, and the node ratio might give prognostic information. Current prospective studies like the LION study (AGO-Ovar) had to investigate if these data have therapeutic implications and may be considered in future staging.