The PI3K Pathway: Background and Treatment Approaches - Lux, Michael P.; Fasching, Peter; Schrauder, Michael G.; Hein, Alexander; Jud, Sebastian; Rauh, Claudia; Beckmann, Matthias (Breast Care, 2016)
Two-thirds of all breast cancer patients with metastases have a hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative subtype. Endocrine therapy is the treatment of choice in these patients since in addition to its effectiveness it can also maintain the patients' quality of life over a longer term. However, 44-62% of postmenopausal patients with metastatic breast carcinoma have primary tamoxifen resistance. After 3-5 years, 30-40% of the patients receiving tamoxifen treatment develop secondary resistance. Understanding the way in which resistance develops is therefore essential for developing treatment approaches that can prevent or reverse endocrine resistance. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway plays a central role here. As a result of the numerous interactions involved, complex issues arise that need to be taken into account in the development and use of therapeutic agents. In addition, this signaling pathway is the one that most frequently undergoes mutations in breast cancer. The prognostic and predictive significance of individual mutations has not yet been fully explained, but it might provide a basis for patient selection in clinical studies. Initial research results on the use of PI3K inhibitors suggest that this may be a highly promising therapeutic approach, with an acceptable side effect profile.
EVALuna2:33003

The placental mTOR-pathway: correlation with early growth trajectories following intrauterine growth restriction? - Fahlbusch, F. B.; Menendez-Castro, C.; Nögel, Stephanie; Marek, I.; Beckmann, Matthias; Schleussner, E.; Ruebner, M.; Huebner, H.; Dörr, Helmuth-Günther; Schild, R. L.; Doetsch, J.; Rascher, Wolfgang; et al. (Journal of Developmental Origins of Health and Disease, 2015)
Idiopathic intrauterine growth restriction (IUGR) is a result of impaired placental nutrient supply. Newborns with IUGR exhibiting postnatal catch-up growth are of higher risk for cardiovascular and metabolic co-morbidities in adult life. Mammalian target of rapamycin (mTOR) was recently shown to function as a placental nutrient sensor. Thus, we determined possible correlations of members of the placental mTOR signaling cascade with auxologic parameters of postnatal growth. The protein expression and activity of mTOR-pathway signaling components, Akt, AMP-activated protein kinase ?, mTOR, p70S6kinase1 and insulin receptor substrate-1 were analysed via western blotting in IUGR v. matched appropriate-for-gestational age (AGA) placentas. Moreover, mTOR was immunohistochemically stained in placental sections. Data from western blot analyses were correlated with retrospective auxological follow-up data at 1 year of age. We found significant catch-up growth in the 1st year of life in the IUGR group. MTOR and its activated form are immunohistochemically detected in multiple placental compartments. We identified correlations of placental mTOR-pathway signaling components to auxological data at birth and at 1 year of life in IUGR. Analysis of the protein expression and phosphorylation level of mTOR-pathway components in IUGR and AGA placentas postpartum, however, did not reveal pathognomonic changes. Our findings suggest that the level of activated mTOR correlates with early catch-up growth following IUGR. However, the complexity of signals converging at the mTOR nexus and its cellular distribution pattern seem to limit its potential as biomarker in this setting.
EVALuna2:17439

The Prevention of Positioning Injuries during Gynecologic Operations. Guideline of DGGG (S1-Level, AWMF Registry No. 015/077, February 2015) - Fleisch, M. C.; Bremerich, D.; Schulte-Mattler, W.; Tannen, A.; Teichmann, A. T.; Bader, W.; Balzer, K.; Renner, Stefan; Roemer, T.; Roth, S.; Schuetz, F.; Thill, M.; et al. (Geburtshilfe und Frauenheilkunde, 2015)
Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.
EVALuna2:17633

The Prevention of Positioning Injuries during Gynecologic SurgeryGuideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/077, October 2020) - Fleisch, Markus C.; Bader, Werner; Balzer, Kai; Bennefeld, Luisa; Boeing, Carsten; Bremerich, Dorothee; Gass, Paul; Geissbuehler, Verena; Koch, Martin; Nothacker, Monika J.; Pietzner, Klaus; Renner, Stefan P.; et al. (Geburtshilfe und Frauenheilkunde, 2021)
Purpose Positioning injuries are relatively common, forensically highly relevant complications of gynecologic surgery. The aim of this official AWMF S2k-guideline is to provide statements and recommendations on how to prevent positioning injuries using the currently available literature. The literature was evaluated by an interdisciplinary group of experts from professional medical societies. The consensus on recommendations and statements was achieved in a structured consensus process. Method The current guideline is based on the expired S1-guideline, which was updated by a systematic search of the literature and a review of relevant publications issued between February 2014 and March 2019. Statements were compiled and voted on by a panel of experts. Recommendations The guideline provides general and specific recommendations on the prevention, diagnosis and treatment of positioning injuries.
CRIS-Team Scopus Importer:2021-04-23
Keywords: gynecologic surgery; positioning injuries; prevention

The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer - Banys-Paluchowski, Malgorzata; Witzel, Isabell; Aktas, Bahriye; Fasching, Peter; Hartkopf, Andreas; Janni, Wolfgang; Kasimir-Bauer, Sabine; Pantel, Klaus; Schoen, Gerhard; Rack, Brigitte; Riethdorf, Sabine; Solomayer, Erich-Franz; et al. (Scientific Reports, 2019)
In breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5-10.5 months] vs. not reached, p < 0.001; PFS:4.8 [95%CI: 3.1-6.5] vs. 9.1 [7.4-10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of >= 5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.
CRIS-Team WoS Importer:2019-03-06

The Randomized AMBORA Trial: Impact of Pharmacological/Pharmaceutical Care on Medication Safety and Patient-Reported Outcomes During Treatment With New Oral Anticancer Agents - Dürr, Pauline; Schlichtig, Katja; Kelz, Carolin; Deutsch, Birgit; Maas, Renke; Eckart, Michael J.; Wilke, Jochen; Wagner, Harald; Wolff, Kerstin; Preuß, Caroline; Brückl, Valeska; Meidenbauer, Norbert; et al. (Journal of Clinical Oncology, 2021)
PURPOSE: Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS: Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug-related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS: Two hundred two patients were included. Antitumor drug-related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION: Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.
CRIS-Team Scopus Importer:2021-07-02

Therapierelevante Biomarker in der gynäkologischen Onkologie - Ditsch, Nina; Fasching, Peter (Best Practice Onkologie, 2022)
The first biomarkers were discovered decades ago. Their prognostic and predictive value is still the subject of current research. Biomarker-based treatments represent the basis of the current and future trial landscape in gynecologic oncology, as was clearly demonstrated at this year’s ASCO Annual Meeting. The all-important question is founded in the quality of diagnostics at the immunohistochemical or molecular level. In breast cancer therapy, a HER‑2 (human epidermal growth factor receptor 2) finding was previously considered therapeutically relevant if there was an immunohistochemical (IHC) evaluation of 3+ or a fluorescence in situ hybridization (FISH)- or chromogenic in situ hybridization (CISH)-positive value. Use of the antibody–drug conjugate trastuzumab–deruxtecan, also in HER-2-low forms (IHC1+ or 2+, even if FISH/CISH negative), is now celebrated as practice changing, since significantly improved progression-free survival (PFS) and overall survival (OS) were also shown in this situation. With the accelerating use of newer therapeutics, attention should be paid to the side effects and the cost–benefit ratio. The following article provides an overview of the currently most important prognostic and predictive markers in breast, ovarian, endometrial, and cervical cancer.
CRIS-Team Scopus Importer:2022-11-11
Keywords: Her-2; Immune checkpoint inhibitors; Immunoconjugates; Microsatellite instability; Prognosis; Trastuzumab

Therapy landscape in patients with metastatic HER2-positive breast cancer: Data from the PRAEGNANT real-world breast cancer registry - Lux, Michael P.; Nabieva, Naiba; Hartkopf, Andreas D.; Huober, Jens; Volz, Bernhard; Taran, Florin-Andrei; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; et al. (Cancers, 2019)
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH ! T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
CRIS-Team Scopus Importer:2019-05-14
Keywords: Advanced breast cancer; Antihormone therapy; Chemotherapy; Her2 c-ERBB2; Her2/neu; Lapatinib; Metastatic; Pertuzumab; T-DM1; Trastuzumab

Therapy response and prognosis of patients with early breast cancer with low positivity for hormone receptors – An analysis of 2765 patients from neoadjuvant clinical trials - Villegas, Sonia L.; Nekljudova, Valentina; Pfarr, Nicole; Engel, Jutta; Untch, Michael; Schrodi, Simone; Holms, Frank; Ulmer, Hans U.; Fasching, Peter; Weber, Karsten E.; Albig, Christian; Heinrichs, Clemens; et al. (European Journal of Cancer, 2021)
Aim: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC. Methods: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1–9%) and strong-positive (ER or PR 10–100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS). We performed RNA sequencing on available tumour tissue samples from patients with low-HR expression (n = 38). Results: Ninety-four (3.4%) patients had low HR-positive tumours, 1769 (64.0%) had strong HR-positive tumours, and 902 (32.6%) had TNBC. There were no significant differences in pCR rates between women with low HR-positive tumours (27.7%) and women with TNBC (35.5%). DFS and DDFS were also not different [for DFS, hazard ratio 1.26, 95%-CI (confidence interval) : 0.87–1.83, log-rank test p = 0.951; for DDFS, hazard ratio 1.17, 95%-CI: 0.78–1.76, log-rank test p = 0.774]. Patients with strong HR-positive tumours had a significantly lower pCR rate (pCR 9.4%; odds ratio 0.38, 95%-CI: 0.23–0.63), but better DFS (hazard ratio 0.48, 95%-CI: 0.33–0.70) and DDFS (hazard ratio 0.49, 95%-CI: 0.33–0.74) than patients with low HR-positive tumours. Molecular subtyping (RNA sequencing) of low HR-positive tumours classified these predominantly into a basal subtype (86.8%). Conclusion: Low HR-positive, HER2-negative tumours have a similar clinical behaviour to TNBC showing high pCR rates and poor survival and also a basal-like gene expression signature. Patients with low HR-positive tumours should be regarded as candidates for therapy strategies targeting TNBC.
CRIS-Team Scopus Importer:2021-03-26
Keywords: Breast cancer; Breast neoplasms; Cancer biomarkers; ER-negative PR-negative HER2-negative breast cancer; Hormone-dependent neoplasms; Mammary cancer; Neoadjuvant therapy; Oestrogen receptors; Progesterone receptors; Triple-negative breast cancer

The Renaissance of Transcervical Balloon Catheters for Cervical Ripening and Labour Induction - Rath, W.; Kehl, Sven (Geburtshilfe und Frauenheilkunde, 2015)
Due to rising rates of labour induction in industrialised countries, safe and effective methods of induction have once again become a focus of interest and research. Prostaglandins are effective for cervical ripening and induction of uterine contractions. They do, however, cause overstimulation of the uterus in up to 20 % of cases, sometimes causing changes in fetal heart rate. Transcervical balloon catheters provide an alternative to prostaglandins for labour induction and have been used for this purpose for almost 50 years. This induction method has experienced a recent renaissance in clinical practice that is reflected in an annually rising number of publications on its use. Balloon catheters allow gentle ripening of the cervix without causing uterine overstimulation. The two catheters available are the Foley catheter (off-label use) and the double balloon catheter, which is licensed for use in induction of labour. Both are as effective as prostaglandins, and do not increase the risk of infection to mother or child. Catheter induction also requires less monitoring compared to prostaglandins resulting in improved patient satisfaction. Balloon catheters provide a useful and promising option to achieve vaginal delivery despite failed prostaglandin induction. Intravenous oxytocin is nevertheless required in up to 85 % of cases for adequate induction/augmentation of contractions. Balloon catheters, vaginal PGE2 and misoprostol are equally effective in the context of an unripe/unfavourable cervix, the rate of uterine hyperstimulation being significantly lower, and the need for oxytocin significantly higher for catheters. Balloon catheters are increasingly being used in combination or sequentially with oral/vaginal misoprostol, although there is currently inadequate published data on the subject. International guidelines recommend the use of balloon catheters for labour induction with an unripe cervix (also following previous caesarean section) as an alternative to prostaglandins, particularly when these are not available or are contraindicated.
EVALuna2:17637

The Role of Hyperthermic Intraperitoneal Chemotherapy in Uterine Cancer Therapy - Psilopatis, Iason; Damaskos, Christos; Garmpis, Nikolaos; Vrettou, Kleio; Garmpi, Anna; Sarantis, Panagiotis; Koustas, Evangelos; Antoniou, Efstathios A.; Kouraklis, Gregory; Chionis, Athanasios; Kontzoglou, Konstantinos; Dimitroulis, Dimitrios (International Journal of Molecular Sciences, 2023)
Endometrial cancer and uterine sarcoma represent the two major types of uterine cancer. In advanced stages, both cancer entities are challenging to treat and correlate with a meagre survival and prognosis. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a form of localized chemotherapy that is heated to improve the chemotherapeutic effect on peritoneal metastases. The aim of the current review is to study the role of HIPEC in the treatment of uterine cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms “hyperthermic intraperitoneal chemotherapy”, “uterine cancer”, “endometrial cancer”, and/or “uterine sarcoma”, we managed to identify 26 studies published between 2004 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HIPEC as treatment modality for peritoneally metastasized uterine cancer. Patients treated with cytoreductive surgery, alongside HIPEC, seem to profit from not only higher survival but also lower recurrence rates. Factors such as the completeness of cytoreductive surgery, the peritoneal cancer index, the histologic subtype, or the applied chemotherapeutic agent, all influence HIPEC therapy effectiveness. In summary, HIPEC seems to represent a promising treatment alternative for aggressive uterine cancer.
CRIS-Team Scopus Importer:2023-08-25
Keywords: cancer; chemotherapy; endometrial; hyperthermic; intraperitoneal; sarcoma; uterine

The Role of Urothelial Cancer-Associated 1 in Gynecological Cancers - Nousiopoulou, Eleni; Vrettou, Kleio; Damaskos, Christos; Garmpis, Nikolaos; Garmpi, Anna; Tsikouras, Panagiotis; Nikolettos, Nikolaos; Nikolettos, Konstantinos; Psilopatis, Iason (Current Issues in Molecular Biology, 2024)
Gynecological cancers (GC) represent some of the most frequently diagnosed malignancies in women worldwide. Long-non-coding RNAs (lncRNAs) are regulatory RNAs increasingly being recognized for their role in tumor progression and metastasis in various cancers. Urothelial cancer-associated 1 (UCA1) is a lncRNA, first found deregulated in bladder cancer, and many studies have exposed its oncogenic effects in more tumors since. However, the role of UCA1 in gynecological malignancies is still unclear. This review aims to analyze and define the role of UCA1 in GC, in order to identify its potential use as a diagnostic, prognostic, or therapeutic biomarker of GC. By employing the search terms “UCA1”, “breast cancer”, “endometrial cancer”, “ovarian cancer”, “cervical cancer”, “vaginal cancer”, and “vulvar cancer” in the PubMed database for the literature review, we identified a total of sixty-three relevant research articles published between 2014 and 2024. Although there were some opposing results, UCA1 was predominantly found to be upregulated in most of the breast, endometrial, ovarian, cervical, and vulvar cancer cells, tissue samples, and mouse xenograft models. UCA1 overexpression mainly accounts for enhanced tumor proliferation and increased drug resistance, while also being associated with some clinicopathological features, such as a high histological grade or poor prognosis. Nonetheless, no reviews were identified about the involvement of UCA1 in vaginal carcinogenesis. Therefore, further clinical trials are required to explore the role of UCA1 in these malignancies and, additionally, examine its possible application as a target for upcoming treatments, or as a novel biomarker for GC diagnosis and prognosis.
CRIS-Team Scopus Importer:2024-04-05
Keywords: cancer; gynecological; UCA1; urothelial cancer-associated 1

The safety and satisfaction of ovarian tissue cryopreservation in prepubertal and adolescent girls - Lotz, Laura; Barbosa, Patricia Reis; Knorr, Christian; Hofbeck, Louisa; Hoffmann, Inge; Beckmann, Matthias; Antoniadis, Sophia; Dittrich, Ralf (Reproductive Biomedicine Online, 2020)
Research question: Is ovarian tissue cryopreservation (OTC) for fertility preservation in prepubertal and adolescent girls safe, and who would benefit most from the procedure? Design: Survey and retrospective study including patients who had OTC under the age of 18 years in a single centre for fertility preservation. Serum anti-Müllerian hormone levels were measured as a marker for detection of diminished ovarian reserve. Results: Fifty-three from 102 women participated in the survey (12 deceased, 19 declined, 17 unreachable, 1 palliative). The average age at OTC was 14.8 ± 2.3 (range: 6–17) years and at survey 21.9 ± 4.3 (range: 16–33) years. Ovarian tissue retrieval (laparoscopy: n = 45, laparotomy: n = 8) was without complications in 52 cases. In 23 (53.5%) of the 43 women who were post-menarchal at OTC, transient amenorrhoea occurred. At survey, 15 women reported a regular menstrual cycle, 25 used oral contraceptives, 9 women reported hormone replacement therapy due to primary ovary insufficiency and 4 had amenorrhoea. Two patients reported the birth of a healthy child after IVF, while 51 patients are still childless, mostly due to their young age (mean: 21.2 years). To date, one patient has had transplantation of the ovarian tissue (17 years at cryopreservation). Forty-nine of the interviewees would again decide on OTC, while three argued against it on the basis of the previous financial cost; one woman was unsure. Conclusions: Children with cancer may be at risk for gonadal insufficiency. OTC is practically the only technique that can be offered to young girls. The procedure is safe and well accepted.
CRIS-Team Scopus Importer:2020-03-27
Keywords: Adolescent females; Cancer; Fertility preservation; Ovarian tissue cryopreservation; Ovarian tissue transplantation; Prepubertal females

The Shear Stress–Regulated Expression of Glypican-4 in Endothelial Dysfunction In Vitro and Its Clinical Significance in Atherosclerosis - Urschel, Katharina; Hug, Karsten; Zuo, Hanxiao; Büttner, Michael; Furtmair, Roman; Kühn, Constanze; Stumpfe, Florian; Botos, Balaz; Achenbach, Stephan; Yuan, Yan; Dietel-Schor, Barbara; Tauchi-Brück, Miyuki (International Journal of Molecular Sciences, 2023)
Retention of circulating lipoproteins by their interaction with extracellular matrix molecules has been suggested as an underlying mechanism for atherosclerosis. We investigated the role of glypican-4 (GPC4), a heparan sulfate (HS) proteoglycan, in the development of endothelial dysfunction and plaque progression; Expression of GPC4 and HS was investigated in human umbilical vein/artery endothelial cells (HUVECs/HUAECs) using flow cytometry, qPCR, and immunofluorescent staining. Leukocyte adhesion was determined in HUVECs in bifurcation chamber slides under dynamic flow. The association between the degree of inflammation and GPC4, HS, and syndecan-4 expressions was analyzed in human carotid plaques; GPC4 was expressed in HUVECs/HUAECs. In HUVECs, GPC4 protein expression was higher in laminar than in non-uniform shear stress regions after a 1-day or 10-day flow (p < 0.01 each). The HS expression was higher under laminar flow after a 1 day (p < 0.001). Monocytic THP-1 cell adhesion to HUVECs was facilitated by GPC4 knock-down (p < 0.001) without affecting adhesion molecule expression. GPC4 and HS expression was lower in more-inflamed than in less-inflamed plaque shoulders (p < 0.05, each), especially in vulnerable plaque sections; Reduced expression of GPC4 was associated with atherogenic conditions, suggesting the involvement of GPC4 in both early and advanced stages of atherosclerosis.
CRIS-Team Scopus Importer:2023-08-11
Keywords: atherosclerosis; endothelial dysfunction; glypican-4; heparan sulfate; plaque; sex differences; shear stress

The significance of transcervical ultrasound-guided radiofrequency ablation in the treatment of symptomatic fibroids: results of an expert consensus from German-speaking countries - Roemer, Thomas; Bends, Ralf; Christoffel, Ladina; Felberbaum, Ricardo; Hildebrandt, Thomas; Meinhold-Heerlein, Ivo; Mueller, Michael; Oppelt, Peter; Renner, Stefan P.; Runnebaum, Ingo B.; Schiermeier, Sven; Piriyev, Elvin; et al. (Archives of Gynecology and Obstetrics, 2022)
Uterine fibroids are one of the most common diseases in female patients, lead mainly to bleeding disorders and lower abdominal pain, and reduce the chance of having children. In recent years we have seen a trend towards more and more pharmacotherapies and minimally invasive organ-preserving treatments. One novel and innovative procedure for an organ-preserving treatment of symptomatic uterine fibroids is the transcervical ultrasound-guided radiofrequency ablation (TRFA). TRFA has been used in Germany since 2013 and later found use in other German-speaking countries as well. There have now been more than 1200 TRFA treatments performed in Germany, Austria, and Switzerland. Experts from these three countries came together for a consensus meeting to analyze the significance of the procedure in the overall concept of the treatment of symptomatic uterine fibroids.
CRIS-Team WoS Importer:2022-04-01

The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients - Fagerholm, Rainer; Schmidt, Marjanka K.; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomaki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Fasching, Peter; Janni, Wolfgang; Weinshilboum, Richard; et al. (Oncotarget, 2015)
We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
EVALuna2:17642

The UGT1A6_19_GG genotype is a breast cancer risk factor - Justenhoven, Christina; Obazee, Ofure; Winter, Stefan; Rabstein, Sylvia; Lotz, Anne; Harth, Volker; Pesch, Beate; Brüning, Thomas; Baisch, Christian; Hartikainen, Jaana M.; Mannermaa, Arto; Kosma, Veli Matti; et al. (Frontiers in Genetics, 2013)
Validation of an association between the UGT1A6_19_T>G (rs6759892) polymorphism and overall breast cancer risk. A pilot study included two population-based case-control studies from Germany (MARIE-GENICA). An independent validation study comprised four independent breast cancer case-control studies from Finland (KBCP, OBCS), Germany (BBCC), and Sweden (SASBAC). The pooled analysis included 7418 cases and 8720 controls from all six studies. Participants were of European descent. Genotyping was done by MALDI-TOF MS and statistical analysis was performed by logistic regression adjusted for age and study. The increased overall breast cancer risk for women with the UGT1A6_19_GG genotype which was observed in the pilot study was confirmed in the set of four independent study collections (OR 1.13, 95% CI 1.05-1.22; p = 0.001). The pooled study showed a similar effect (OR 1.09, 95% CI 1.04-1.14; p = 0.001). The risk effect on the basis of allele frequencies was highly significant, the pooled analysis showed an OR of 1.11 (95% CI 1.06-1.16; p = 5.8 × 10-6). We confirmed the association of UGT1A6_19_GG with increased overall breast cancer risk and conclude that our result from a well powered multi-stage study adds a novel candidate to the panel of validated breast cancer susceptibility loci. © 2013 Justenhoven, Obazee, Winter, Rabstein, Lotz, Harth, Pesch, Brüning, Baisch, Hartikainen, Mannermaa, Kosma, Kataja, Winqvist, Pylkäs, Jukkola-Vuorinen, Grip, Fasching, Beckmann, Ekici, Hein, Hall, Li, Chang-Claude, Flesch-Janys, Seibold, Rudolph, Hamann, Ko and Brauch.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Breast cancer risk; Metabolism; Polymorphism; UGT1A6; Validation

The Use of Assisted Reproductive Technology by European Childhood Cancer Survivors - Borgmann-Staudt, Anja; Michael, Simon; Sommerhaeuser, Greta; Fernandez-Gonzalez, Marta-Julia; Friedrich, Lucia Alacan; Klco-Brosius, Stephanie; Kepak, Tomas; Kruseova, Jarmila; Michel, Gisela; Panasiuk, Anna; Schmidt, Sandrin; Lotz, Laura; et al. (Current Oncology, 2022)
CCS often wish to have biological children yet harbour concerns about fertility impairment, pregnancy risks and the general health risks of prospective offspring. To clarify these concerns, health outcomes in survivor offspring born following ART (n = 74, 4.5%) or after spontaneous conception (n = 1585) were assessed in our European offspring study by descriptive and bivariate analysis. Outcomes were compared to a sibling offspring cohort (n = 387) in a 4:1 matched-pair analysis (n = 1681). (i) Survivors were more likely to employ ART than their siblings (4.5% vs. 3.7%, p = 0.501). Successful pregnancies were achieved after a median of one cycle with, most commonly, intracytoplasmic sperm injection (ICSI) using non-cryopreserved oocytes/sperm. (ii) Multiple-sibling births (p < 0.001, 29.7% vs. 2.5%), low birth weight (p < 0.001; OR = 3.035, 95%-CI = 1.615–5.706), and preterm birth (p < 0.001; OR = 2.499, 95%-CI = 1.401–4.459) occurred significantly more often in survivor offspring following ART utilisation than in spontaneously conceived children. ART did not increase the prevalence of childhood cancer, congenital malformations or heart defects. (iii) These outcomes had similar prevalences in the sibling population. In our explorative study, we could not detect an influence on health outcomes when known confounders, such as multiple births, were taken into account.
CRIS-Team Scopus Importer:2022-09-09
Keywords: ART; cancer; childhood and adolescence; health outcome; offspring; survivor

The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration - Kehl, Sven; Weiss, Christel; Pretscher, Jutta; Baier, Friederike; Faschingbauer, Florian; Beckmann, Matthias; Stumpfe, Florian (Journal of Perinatal Medicine, 2021)
Objectives: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. Methods: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). Results: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). Conclusions: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.
CRIS-Team WoS Importer:2021-12-03

The villoglandular Adenocarcinoma of the Cervix as a Tumor Model. A Literature Analysis - Dietl, Anna; Aumann, K.; Beckmann, Matthias (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

The Work- and Further Training Situation of young Doctors in Further Training in Gynecology - A Standpoint - Lermann, Johannes; Knabl, J.; Neimann, J.; Schulte, K.; Proske, K.; Schott, S.; Raspe, M. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

The work and training situation for young physicians undergoing specialty training in gynecology and obstetrics in Germany: an assessment of the status quo - Lermann, Johannes; Knabl, Julia; Neimann, Johannes; Schulte, Kevin; Proske, Kim; Schott, Sarah; Raspe, Matthias (Archives of Gynecology and Obstetrics, 2020)
Purpose: General conditions in the health-care system in Germany have changed dramatically in recent years. Factors affecting this include above all demographic change, rapid developments in diagnostic and therapeutic options, and the application of economic criteria to the health-care sector. This study aimed to establish the current status quo regarding conditions of work and training for young doctors in gynecology and obstetrics, analyze stress factors, and suggest potential improvements. Methods: Between October 2015 and March 2016, a web-based survey was carried out among residents and members of the German Society for Gynecology and Obstetrics. The electronic questionnaire comprised 65 items on seven topics. Part of the survey included the short version of a validated model of professional gratification crises for analyzing psychosocial work-related stress. Results: The analysis included a total of 391 complete datasets. Considerable negative findings in relation to psychosocial work pressure, time and organizational factors, quality of specialty training, and compatibility between work and family life and work and academic tasks were detected. A high level of psychosocial work pressure is associated with more frequent job changes, reduced working hours, poorer health among physicians, and a lower subjectively assessed quality of care. Conclusions: Greater efforts are needed from all the participants involved in patient care to achieve high-quality training and working conditions that allow physicians to work in a healthy and effective way. These aspects are all prerequisites for sustainably maximizing the resource “physician” and for ensuring high-quality patient care.
CRIS-Team Scopus Importer:2020-06-05
Keywords: Gynecology and obstetrics; Medical specialty training; Psychosocial work pressure; Stress factors; Working conditions

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes - Würfel, Franziska; Erber, Ramona; Hübner, Hanna; Hein, Alexander; Lux, Michael P.; Jud, Sebastian; Kremer, Anita; Kranich, Hannah; Mackensen, Andreas; Häberle, Lothar; Hack, Carolin; Rauh, Claudia; et al. (Breast Care, 2018)
Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.<br

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes - Würfel, Franziska; Erber, Ramona; Hübner, Hanna; Hein, Alexander; Lux, Michael P.; Jud, Sebastian; Kremer, Anita; Kranich, Hannah; Mackensen, Andreas; Häberle, Lothar; Hack, Carolin; Rauh, Claudia; et al. (Breast Care, 2018)
Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triplenegative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype 'lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach. (C) 2018 S. Karger GmbH, Freiburg
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TILGen study-immunological targets in patients with breast cancer : Influence of tumor-infiltrating lymphocytes - Erber, Ramona; Hartmann, Arndt; Beckmann, Matthias; Mackensen, Andreas; Kremer, Anita; Reimann, Hannah; Hübner, Hanna; Hein, Alexander; Lux, Michael P.; Jud, Sebastian; Häberle, Lothar; Gaß, Paul; et al. (Pathologe, 2018)
BACKGROUND: The interaction of our immune system with breast cancer (BC) cells prompted the investigation of tumor-infiltrating lymphocytes (TILs) and targeted, tumor antigen-specific immunotherapy. OBJECTIVES: Correlation between TILs and pathological complete response (pCR) after neoadjuvant systemic therapy (NACT). Tumor-specific antigens (TSAs) in HER2+ and triple negative BC and establishment of TSA-specific therapies within the interdisciplinary TILGen study. METHODS: Illustration of the TILGen study design. Assessment of TILs and correlation with pCR within this BC study. RESULTS: pCR was achieved in 38.4% (56/146) and associated with estrogen receptor/progesterone receptor negative (ER-/PR-) and HER2+ tumors. Lymphocytic predominant BC (LPBC) was found in 16.4% (24/146), particularly in ER-/PR- (ER-: 27.3% vs. ER+: 9.9%, PR-: 22.3% vs. PR+: 8.2%), large, and poorly differentiated BC. TILs were significantly correlated with pCR in multivariate analysis. In LPBC, pCR was achieved in 66.7%, whereas it was 32.8% in non-LPBC. CONCLUSIONS: First results confirm the influence of the human immune system on the response to NACT in HER2+ and triple negative BC. TSA-specific immunotherapy might improve the outcome in BC patients but there is an urgent need for comprehensive studies to further investigate this issue.
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Time and Resources Needed to Document Patients with Breast Cancer from Primary Diagnosis to Follow-up - Results of a Single-center Study - Lux, Michael P.; Sell, C. S.; Fasching, Peter; Seidl-Ertel, Janine; Bani, Mayada; Schrauder, M. G.; Jud, Sebastian; Löhberg, Christian; Rauh, C.; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Strnad, Vratislav; et al. (Geburtshilfe und Frauenheilkunde, 2014)
Aim: Certification of breast centers helps improve the quality of care but requires additional resources, particularly for documentation. There are currently no published data on the actual staff costs and financial resources required for such documentation. The aim of this study was to determine the time and resources required to document a patient with primary breast cancer from diagnosis to the end of follow-up, to establish a database for future strategic decisions. Material and Methods: All diagnostic and therapeutic procedures of patients with primary breast cancer were recorded at the University Breast Center of Franconia. All time points for documentation were evaluated using structured interviews. The times required to document a representative number of patients were determined and combined with the staff costs of the different professional groups, to calculate the financial resources required for documentation. Results: A total of 494 time points for documentation were identified. The study also identified 21 departments and 20 different professional groups involved in the documentation. The majority (54 %) of documentation was done by physicians. 62 % of all documentation involved outpatients. The results of different scenarios for the diagnosis, therapy and follow-up of breast cancer patients in a certified breast center showed that the time required for documentation can be as much as 105 hours, costing EUR 4135. Conclusion: This analysis shows the substantial staffing and financial costs required for documentation in certified centers. A multi-center study will be carried out to compare the costs for certified breast centers of varying sizes with the costs of non-certified care facilities.
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Timing of sequential use of double-balloon catheter and oral misoprostol for induction of labor - Kehl, Sven; Böhm, Lea; Weiss, Christel; Heimrich, Jutta; Dammer, Ulf; Baier, Friederike; Suetterlin, Marc; Beckmann, Matthias; Faschingbauer, Florian (Journal of Obstetrics and Gynaecology Research, 2016)
AIM: The best time to commence cervical ripening with a balloon catheter is unknown. The aim of this study was to evaluate whether application of a balloon catheter in the morning or in the evening is better when sequential prostaglandin application is planned. METHODS: This multicenter historical cohort study included 415 women with an unfavorable cervix undergoing labor induction at term. Labor was induced with a double-balloon catheter and the sequential use of oral misoprostol if necessary. The balloon catheter was placed in the morning group between 02:00-15:00 and in the evening group between 15:00-02:00. The primary outcome measure was the cesarean section rate. Secondary outcome measures included failed labor induction (no vaginal delivery within 72 h). RESULTS: The cesarean section rate did not differ between the groups (morning 26.9%, evening 24.3%; P = 0.5553); however, more women in the morning group did not deliver within 72 h (8.8% vs 3.1%; P = 0.0138). In nulliparous women, labor induction failed more often in the morning group (12% vs. 4%, P = 0.043). In parous women, the induction-to-delivery interval was longer in the morning group (1756 vs. 1349 min; P = 0.046), and there were fewer deliveries within 24 h (35% vs. 56%, P = 0.016). CONCLUSIONS: When sequential use of a double-balloon catheter and oral misoprostol for labor induction is planned, the preferable time for catheter placement is in the evening. This resulted in fewer failed inductions in nulliparous women and a shorter induction-to-delivery interval and more deliveries within 24 h in parous women.
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Tissue Engineering of Lymphatic Vasculature in the Arteriovenous Loop Model of the Rat - Robering, Jan Willem; Al-Abboodi, Majida; Titzmann, Adriana; Horn, Inge; Beier, Justus; Horch, Raymund E.; Kengelbach-Weigand, Annika; Boos, Anja (Tissue Engineering - Part A, 2020)
Various therapeutic approaches, for example, in case of trauma or cancer require the transplantation of autologous tissue. Depending on the size and the origin of the harvested tissue, these therapies can lead to iatrogenic complications and donor-site morbidities. In future, these side effects could be avoided by transplanting artificially generated tissue consisting of different cell types and matrix components derived from the host body. Tissue that is grown in the patient could be advantageous compared with the more simply structuredin vitro-grown alternatives. To overcome the limitations of graft vascularization, the arteriovenous (AV) loop technique has been established for different tissues in the last years and was adapted for lymphatic tissue engineering in the present study. We utilized the AV loop technique to grow human lymphatic vasculaturein vivoin the Rowett nude (RNU) rat. A combination of human lymphatic endothelial cells (LECs) and bone marrow-derived mesenchymal stem cells was implanted in a fibrin matrix surrounding the AV loop. After 2 or 4 weeks of implantation, the animals were perfused and the tissue was harvested. It could be demonstrated by immunohistochemistry for human LYVE1, human CD31, and murine podoplanin that the implanted cells formed human lymphatic vasculature in the AV loop chamber. Beside development of murine podoplanin-positive vasculature in the AV loop tissue, vasculature positive for human marker proteins developed in comparable numbers. This suggests that implanted LECs are able to improve the lymphatic vascularization of the newly engineered tissue. Thus, we were able to establish anin vivotissue engineering method to generate lymphatic vascularized soft tissue. An axially vascularized transplantable lymphatic vessel network was engineered without requiring advanced cell culture equipment, rendering the lymphatic AV loop highly suitable for applied regenerative medicine. Impact statement Various surgical procedures require the transplantation of autologous harvested tissue, for example, the vascularized lymph node transfer for the treatment of lymphedema. Tissue-engineered transplants could be used instead of autologous transplants and thereby help to reduce the side effects of those therapies. However,in vitrotissue engineering of large constructs requires a lot of know-how as well as advanced cell culture equipment, which might not be accessible in every hospital.In vivotissue engineering approaches like the presented technique for the generation of transplantable networks of lymphatic vasculature could serve as an alternative forin vitrotissue engineering approaches in clinical settings.
CRIS-Team WoS Importer:2020-10-16

Tomosynthese - Schulz-Wendtland, Rüdiger; Beckmann, Matthias; Fasching, Peter; Uder, Michael (Chirurgische Praxis, 2016)
Full field digital mammography (FFDM) is the most important method for early diagnosis of breast cancer. The typical overlapping of normal and pathological tissue during the standard 2D projection, however, often reduces the specificity and sensitivity of the mammographic investigation. Digital breast tomosynthesis (DBT) provides on the basis of a limited number of single images with different projection angles not superimposed tomograms and may remove the unwanted masking by superimposed structures. Clinical studies show that the digital tomosynthesis has the real potential to reduce the recall rate and simultaneously increase the cancer detection rate, especially in women with dense breasts (detection and volumetry). The use of tomosynthesis seems to be superior to full field digital mammography in mammography screening. Other possibilities of the tomosynthesis are the dual energy mammography, contrast medium-enhanced mammography and intervention.
CRIS-Team Scopus Importer:2023-03-08
Keywords: Contrast medium-enhanced mammography; Dual energy mammography; Full-field digital mammography; Intervention; Mammography screening; Tomosynthesis

Torsional osteotomies of the femur - Dickschas, Jörg; Harrer, Jörg; Reuter, Benoit; Schwitulla, Judith; Strecker, Wolf (Journal of Orthopaedic Research, 2015)
Various pathologies of the hip or knee, such as patellofemoral malalignment or femoroacetabular impingement may be caused by a femoral torsional deformity. When diagnosed and analyzed, it is treated by femoral torsional osteotomy. Thirty femoral torsional osteotomies in 25 patients were included, the principal symptoms were patellar dislocation in 15 patients, anterior knee pain in 17, and femoroacetabular impingement in two. A computed-tomography-based measurement of the torsional angle was performed in all patients. Japanese Knee Society score, Tegner activity score, Lysholm score, and visual analog scale score were determined before surgery and at follow-up after 41 (6-113) months. Femoral internal torsion was on average 40.9° (29° - 66°; normal 24°). Surgical treatment consisted of a femoral external torsional osteotomy of on average 13.8° (5° - 26°). Tegner activity score increased non-significantly (p-value 0.326) from 3.57 to 3.71. Japanese Knee Society score improved significantly from 72 to 87 (p-value 0.004) while Lysholm score rose significantly from 66 to 84 points (p-value 0.004). Pain relief was demonstrated by a significant decrease in the VAS score from 5.6 to 2.4 (p-value 0.007). No further patellar dislocation was reported. Torsional deformities of the femur frequently cause symptoms in the knee or hip joint. After thorough assessment and diagnostic investigation, a femoral external torsional osteotomy provides significant pain relief as well as patellofemoral stability. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???-???, 2015.
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Total laparoscopic hysterectomy: how does training for surgeons in a standardized operation affect hospitals and patients? - Hildebrandt, Thomas; Emir, Seher; Boosz, Alexander; Beckmann, Matthias; Mueller, Andreas (Archives of Gynecology and Obstetrics, 2018)
PURPOSE: Surgical training usually means inexperienced physicians initially doing operations supervised by an experienced physician, to gain the experience and skills needed to conduct surgery independently. Various issues arise here for both hospitals and patients. Are training procedures associated with higher complication rates, blood losses, and transfusion rates? What does training in the operating room ultimately cost in terms of valuable surgical time? Do longer hospitalization periods potentially mean financial losses for the hospital under the diagnosis-related groups (DRG) system? METHODS: A retrospective analysis was carried out of data for 571 patients who underwent total laparoscopic hysterectomy (TLH) in the Department of Gynecology at the University of Erlangen from 2009 to 2012, with/without adnexectomy, due to benign indication; and of data for 255 patients who underwent the same procedures in Karlsruhe Municipal Hospital in 2013-2014. The patients were classified into two groups: those in whom surgery was carried out by experienced specialists who had carried out at least 40 independent operations; and those in whom it was carried out by a trainee resident who had personally done fewer than 40 operations. RESULTS: In the two groups, the patients had similar mean body mass indexes, uterus weights, and blood losses. Patients in the specialist group were slightly older. There were no differences in complication rates. Over two-thirds of complications occurred in patients with previous surgery. Procedures by residents took significantly longer. Hospitalization periods in both groups were still below the mean threshold length of stay under Germany's DRG system, so that no income losses occurred even with training procedures. CONCLUSIONS: Training and teaching operations supervised by experienced surgeons are just as safe as operations by experienced surgeons themselves. Interpretation of these data is of course limited by the retrospective study design; patients treated by specialists tended to have more prior operations and were older, with a trend toward larger uteri. Surgical training, as the example of TLH in benign indication shows here, involves an additional time of approximately 10-20 min per operation. With regard to the revenue situation, the hospitalization periods in both groups were within the profit zone for the hospital concerned.
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Touch Imprint Cytology and Stereotactically-Guided Core Needle Biopsy of Suspicious Breast Lesions: 15-Year Follow-up - Schulz-Wendtland, Rüdiger; Fasching, Peter; Bani, Mayada; Lux, Michael P.; Jud, Sebastian; Rauh, C.; Bayer, C.; Wachter, David; Hartmann, Arndt; Beckmann, Matthias; Uder, Michael; Löhberg, Christian (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions.
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Touch imprint cytology of core needle biopsy specimens for the breast and quick stain procedure for immediate diagnosis - Kehl, Sven; Mechler, Christina; Menton, Susanne; Weiss, Christel; Wasgindt, Sabine; Suetterlin, Marc; Trunk, Marcus (Anticancer Research, 2014)
To investigate the validity and reproducibility of touch imprint cytology (TIC) of core needle biopsies (CNBs) in the assessment of conspicuous breast findings.One hundred and fifty-eight conspicuous breast findings were assessed by CNB during a two-year period in this prospective study. TIC of the CNBs was used for cytological analysis. The performance of this technique was evaluated by comparing the results with the histology of the CNB, and in cases of a subsequent surgery, with the final histology. In addition, inter-observer reproducibility was analyzed.The inter-observer variability was very high (kappa-value of 0.8508; excluding inadequate imprints, 0.9502). Inadequate cellularity for cytological analysis was found in 11.4% (18/158) of findings. Compared with CNB histology, the sensitivity, specificity, positive predictive value, negative predictive value and overall accuracy of TIC was 99%, 100%, 100%, 94%, and 99%, respectively.TIC of CNB specimens of the breast may be a valid option for providing a diagnosis without delay for a histological procedure, assuming good quality of the specimen.
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Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes - Newe, Axel; Wimmer, Stefan; Neubert, Antje; Becker, Linda; Prokosch, Hans-Ulrich; Beckmann, Matthias; Fietkau, Rainer; Forster, Christian; Neurath, Markus; Schett, Georg; Ganslandt, Thomas (PLoS ONE, 2015)
Background The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. Methods In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. Result The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. Discussion The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With this lab value curve data as a basis, algorithms for detecting temporal relationships can be developed, and with the classification made by human experts, these algorithms can immediately be validated. Due to the normalization of the lab value data, it allows for a generic approach rather than for specific or solitary drug/lab value combination

Toxic effect of light on oocyte and pre-implantation embryo: a systematic review - Khodavirdilou, Rasa; Pournaghi, Marjaneh; Oghbaei, Hajar; Rezaei, Yeganeh Rastgar; Javid, Farzin; Khodavirdilou, Lida; Shakibfar, Farah; Latifi, Zeinab; Hakimi, Parvin; Nouri, Mohammad; Fattahi, Amir; Dittrich, Ralf (Archives of Toxicology, 2021)
In the female reproductive tract, oocytes and embryos are in a dark environment, while during the in vitro fertilization (IVF) they are exposed to various visible and invisible lights such as daylight, microscope, and laminar hood fluorescent lights. Studies have shown that light could damage cellular compartments of oocytes and embryos and consequently decrease rates of fertilization, development, and blastocyst formation. However, due to the lack of consensus about the effects of light on the embryos, and subsequently the inability to make definitive decisions regarding the light exposure management to improve IVF results, in the present study, we systematically reviewed the effect of light with different wavelengths and intensities on pre-implantation embryos. The toxic impact of light depends on the wavelength, intensity, and duration of light exposure and also the stage of embryo. Therefore, reducing the observation time of embryos out of the incubator and also using light filters can alleviate the detrimental effect of light in IVF labs.
CRIS-Team WoS Importer:2021-09-10

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial - Schroeder, L.; Rack, B.; Sommer, H.; Koch, J. G.; Weissenbacher, T.; Janni, W.; Schneeweiss, A.; Rezai, M.; Lorenz, R.; Jaeger, B.; Schramm, A.; Häberle, Lothar; et al. (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients.Methods:Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support.Results:No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2 %), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm.Conclusion:The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.
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Toxoplasma gondii Infection in Pregnancy - Recommendations of the Working Group on Obstetrics and Prenatal Medicine (AGG - Section on Maternal Disorders) - Schneider, Michael; Faschingbauer, Florian; Kagan, Karl Oliver; Groβ, Uwe; Enders, Martin; Kehl, Sven (Geburtshilfe und Frauenheilkunde, 2023)
Aim The AGG (Working Group for Obstetrics and Prenatal Diagnostics, Section Maternal Diseases) has issued these recommendations to improve the detection and management of Toxoplasma gondii infection in pregnancy. Methods Members of the Task Force developed the recommendations and statements presented here using recently published literature. The recommendations were adopted after a consensus process by members of the working group. Recommendations This article focuses on the epidemiology and pathophysiology of Toxoplasma gondii infection in pregnancy and includes recommendations for maternal and fetal diagnosis, transmission prophylaxis, therapy, prevention, screening, and peripartum management.
CRIS-Team Scopus Importer:2023-10-20
Keywords: congenital toxoplasmosis; pregnancy; therapy; Toxoplasma gondii; transmission

TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer - Fagerholm, Rainer; Khan, Sofia; Schmidt, Marjanka K.; Garcia-Closas, Montserrat; Heikkila, Pavi; Saarela, Jani; Beesley, Jonathan; Jamshidi, Maral; Aittomaki, Kristiina; Liu, Jianjun; Ali, H. Raza; Andrulis, Irene L.; et al. (Oncotarget, 2017)
TP53 overexpression is indicative of somatic TP53 mutations and associates with aggressive tumors and poor prognosis in breast cancer. We utilized a two-stage SNP association study to detect variants associated with breast cancer survival in a TP53-dependent manner. Initially, a genome-wide study (n = 575 cases) was conducted to discover candidate SNPs for genotyping and validation in the Breast Cancer Association Consortium (BCAC). The SNPs were then tested for interaction with tumor TP53 status (n = 4,610) and anthracycline treatment (n = 17,828). For SNPs interacting with anthracycline treatment, siRNA knockdown experiments were carried out to validate candidate genes.In the test for interaction between SNP genotype and TP53 status, we identified one locus, represented by rs10916264 (p(interaction) = 3.44 × 10-5; FDR-adjusted p = 0.0011) in estrogen receptor (ER) positive cases. The rs10916264 AA genotype associated with worse survival among cases with ER-positive, TP53-positive tumors (hazard ratio [HR] 2.36, 95% confidence interval [C.I] 1.45 - 3.82). This is a cis-eQTL locus for FBXO28 and TP53BP2; expression levels of these genes were associated with patient survival specifically in ER-positive, TP53-mutated tumors. Additionally, the SNP rs798755 was associated with survival in interaction with anthracycline treatment (p(interaction) = 9.57 × 10-5, FDR-adjusted p = 0.0130). RNAi-based depletion of a predicted regulatory target gene, FAM53A, indicated that this gene can modulate doxorubicin sensitivity in breast cancer cell lines.If confirmed in independent data sets, these results may be of clinical relevance in the development of prognostic and predictive marker panels for breast cancer.
EVALuna2:36150

Transcriptome-wide association study of breast cancer risk by estrogen-receptor status - Feng, Helian; Gusev, Alexander; Pasaniuc, Bogdan; Wu, Lang; Long, Jirong; Abu-Full, Zomoroda; Aittomaki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Antoniou, Antonis C.; Arason, Adalgeir; Arndt, Volker; et al. (Genetic Epidemiology, 2020)
Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer.
CRIS-Team Scopus Importer:2020-03-20
Keywords: breast cancer subtype; causal gene; GWAS; TWAS

Translational Highlights in Breast and Ovarian Cancer 2019 – Immunotherapy, DNA Repair, PI3K Inhibition and CDK4/6 Therapy - Hartkopf, Andreas D.; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Schuetz, Florian; Fasching, Peter; Kolberg, Hans-Christian; Welslau, Manfred; Overkamp, Friedrich; et al. (Geburtshilfe und Frauenheilkunde, 2019)
In the near future, important translational questions of clinical relevance will be adressed by studies currently in progress. On the one hand, the role of PD-L1 expression must be further understood, after it was found to be relevant in the use of atezolizumab in first-line therapy of patients with metastatic triple-negative breast cancer (TNBC). No association between efficacy and PD-L1 expression was found in a neoadjuvant study that included pembrolizumab in TNBC. The pathological complete response rate (pCR) was higher in both patient groups with and without PD-L1 expression when pembrolizumab was added to chemotherapy. Another future question is the identification of further patient groups in which efficacy of PARP inhibitors is seen, which are licensed for the pBRCA1/2 germline mutation. These include, for example, patients with mutations in other genes, which are involved in homologous recombination, or patients with tumours that show an abnormality in global tests of homologous recombination deficiencies (HRD tests). The question of whether a PARP inhibitor can be given and with which chemotherapy combination partners is currently being investigated in both breast and ovarian cancer. While the data on improved overall survival are being consolidated for the CDK4/6 inhibitors, knowledge of molecular changes during the therapy and during progression on the therapy is growing. Both the accumulation of PI3K mutations and also PTEN changes might play a part in planning subsequent therapies. This review article summarises these recent developments in breast cancer and in part also in ovarian cancer.
CRIS-Team WoS Importer:2020-01-17

Translational highlights in breast cancer research and treatment: recent developments with clinical impact - Fasching, Peter; Schneeweiss, Andreas; Kolberg, Hans-Christian; Ettl, Johannes; Fehm, Tanja N.; Overkamp, Friedrich; Lueftner, Diana (Current Opinion in Obstetrics & Gynecology, 2019)
Purpose of review Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments. This review focuses on recent developments in the prevention and treatment of breast cancer including results from major clinical trials and recent conferences. Recent findings Many pathways involved in the progression or treatment of breast cancer have been also identified in the cause and pathogenesis of breast cancer. Therefore, breast cancer risk can be described in much more detail, possibly leading to new prevention strategies. In breast cancer treatment the introduction of PARP inhibitors has begun. Recent trials will lead to a better understanding whether PI3K inhibitors can be developed for application in the clinic and first large randomized trials show the superiority of anti PD-1/PD-L1 treatments. Treatment strategies which were developed over the last decade are moving rapidly into the clinical use. The understanding of treatment targets and involved side effects will be important for the safe implementation of these treatments into routine practice.
CRIS-Team WoS Importer:2019-04-12

Transplantation of ovarian tissue to postpone menopause - is it really more advantageous for women's health than menopause hormone therapy? - Von Wolff, Michael; Dittrich, Ralf; Stute, Petra (Reproductive Biomedicine Online, 2015)
EVALuna2:17553

Transplantation of refreezed ovarian tissue after unexpected occurrence of endometriosis - Dietl, Anna; Dittrich, Ralf; Hoffmann, Inge; Denschlag, D.; Hanjalic-Beck, A.; Mueller, A.; Beckmann, Matthias; Lotz, Laura (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Trastuzumab Biosimilars in the Therapy of Breast Cancer – “Real World” Experiences from four Bavarian University Breast Centres - Hester, Anna; Gaß, Paul; Fasching, Peter; Kraemer, Anne Katrin; Ettl, Johannes; Diessner, Joachim; Woeckel, Achim; Egger, Tobias; Stock, Katja; Redlin, Jutta; Andraschko, Monika; Harbeck, Nadia; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Introduction With the introduction of the first trastuzumab biosimilar in the summer of 2018, biosimilar antibodies for breast cancer have found their way into the area of gynaecological oncology. The switch of anti-human epidermal growth factor receptor 2 (HER2) therapy from the reference drug Herceptin ® to a biosimilar has presented challenges to the clinics. In addition to structural and organisational measures, training of employees as well as patient briefing and acceptance were major challenges. The study presented here records - within the context of quality assurance - how the switch to a trastuzumab biosimilar was implemented at four Bavarian university clinics in the Purchasing Association of Bavarian University Pharmacies. Materials/Methods Questionnaires on treatment figures and the switching process were sent to breast centres and pharmacies of four Bavarian university clinics between July and December 2019. The neoadjuvant, adjuvant and metastasised anti-HER2 therapy with trastuzumab with or without pertuzumab was recorded, evaluated and summarised. Results In the anti-HER2-therapy, trastuzumab was used intravenously (i. v.) and subcutaneously. Between July and December 2018, all four clinics in the Purchasing Association switched the i. v. trastuzumab therapy from the reference drug (Herceptin) to a biosimilar (for 2018: Kanjinti ®). Over 200 patients were treated with trastuzumab i. v. in each of the two half-years of 2018 (before and after the switch). The spectrum of side effects and pCR rates under therapy with the biosimilar were comparable to the experiences made with the reference drug. Three out of four clinics provided training to employees and informed patients by means of a defined information leaflet. Patient acceptance was high. Summary The anti-HER2 therapy could be switched successfully and safely to trastuzumab biosimilars at the Bavarian university hospitals. This may serve as guideline for the further implementation of biosimilars. The structures necessary for this initial switching process have been prepared with trastuzumab as an example.
CRIS-Team Scopus Importer:2020-12-18
Keywords: biosimilar; breast cancer; HER2; pCR; trastuzumab

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer - Von Minckwitz, G.; Huang, C. -S.; Mano, M. S.; Loibl, S.; Mamounas, E. P.; Untch, M.; Wolmark, N.; Rastogi, P.; Schneeweiss, A.; Redondo, A.; Fischer, H. H.; Jacot, W.; et al. (New England Journal of Medicine, 2019)
BACKGROUND
CRIS-Team WoS Importer:2019-02-27

Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial - Ignatiadis, M.; Litiere, S.; Rothe, F.; Riethdorf, S.; Proudhon, C.; Fehma, T.; Aalders, K.; Forstbauer, H.; Fasching, Peter; Brain, E.; Vuylsteke, P.; Guardiola, E.; et al. (Annals of Oncology, 2018)
Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer.The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and >=1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of >=1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety.Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm.Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.
EVALuna2:56170

TREAT CTC: An innovative therapy approach to eliminate circulating tumor cells (CTCs) - Tzschaschel, M.; Trapp, E.; Rack, B.; Messina, C.; Mueller, V.; Fehm, T.; Janni, W.; Löhberg, Christian; Wimberger, P.; Kolberg, H. -C.; Uleer, C.; Brudler, O.; et al. (2016)
EVALuna2:33466

Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry - Witzel, I.; Laakmann, E.; Weide, R.; Neunhoeffer, T.; Park-Simon, T. -J.; Schmidt, Marcus; Fasching, Peter; Hesse, T.; Polasik, A.; Mohrmann, S.; Wuerschmidt, F.; Schem, C.; et al. (European Journal of Cancer, 2018)
Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.Median age at diagnosis of BMs was 56 years (22-90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%), whereas the percentage of patients with luminal-like tumours increased (28%-34%; p = 0.0331). Patients with BMs in the posterior fossa were more often HER2 positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n = 65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p < 0.0001). Median overall survival (OS) time after development of BMs for the overall cohort was 7.4 months (95% confidence interval [CI]: 6.7-8.0 months). One-year survival rate was 37.7% (95% CI: 35.2-40.1). Patients with HER2-positive tumours had the longest median OS of 11.6 months (95% CI: 10.0-13.4) compared with 5.9 months (95% CI: 5.0-7.2) for patients with luminal-like and 4.6 months (95% CI: 3.9-5.4) for patients with triple-negative tumours. Patients with HER2-positive tumours who received anti-HER2 treatment had longer median OS than those without (17.1 months versus 7.2 months, p < 0.0001).Prognosis of patients after developing BMs varies significantly according to the subtype. The outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2-negative patients. Our results underline the high medical need for improvement of treatment and prevention strategies for BMs in breast cancer patients.
EVALuna2:56176

Treatment landscape and prognosis after treatment with trastuzumab emtansine - Laakmann, Elena; Emons, Julius; Taran, Florin Andrei; Janni, Wolfgang; Uhrig, Sabrina; Overkamp, Friedrich; Kolberg, Hans Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Lüftner, Diana; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Purpose Pertuzumab and T-DM1 are two efficient anti-HER2 treatments for patients with HER2-positive advanced breast cancer. While pertuzumab is usually given in first-line treatment and T-DM1 in second-line treatment, standard therapy options seem to be exhausted up to now after the treatment of patients with these two therapy options. Therefore, it is important to have data that describes the therapy situation and prognosis after T-DM1 treatment. Methods The PRAEGNANT metastatic breast cancer registry (NCT02338167) is a prospective registry for breast cancer patients with a focus on molecular biomarkers. Patients of all therapy lines with any kind of treatment are eligible. Collected data comprises therapies, adverse events, quality of life and other patient reported outcomes. Here we report on the patient characteristics and descriptive prognostic data for HER2-positive patients who have completed a treatment with T-DM1. Therapy patterns after T-DM1 and progression-free survival are reported as well as overall survival. Results A total of 85 patients were identified for the study who were prospectively observed during therapy after the termination of T-DM1. The main reason for T-DM1 termination was progress. Following T-DM1, lapatinib, trastuzumab and chemotherapy were the main therapy choices. Median progression-free survival was 4.8 months (95% CI: 3.2-6.3) and median overall survival was 18.4 months (95% CI: 15.5-21.3). Conclusions Therapy options after T-DM1 in a real-world setting seem to exhibit a relevant clinical efficacy, supporting the concept of continuous anti-HER2 treatments in the advanced therapy setting for breast cancer patients. Novel therapies are needed to improve the rather short median progression-free survival.
CRIS-Team Scopus Importer:2020-11-20
Keywords: advanced breast cancer; antihormone therapy; chemotherapy; HER2 c-erbB2; HER2/neu; lapatinib; metastatic; pertuzumab; T-DM1; trastuzumab

Treatment landscape of advanced breast cancer patients with hormone receptor positive HER2 negative tumors - Data from the German PRAEGNANT breast cancer registry - Hartkopf, Andreas D.; Huober, Jens; Volz, Bernhard; Nabieva, Naiba; Taran, Florin-Andrei; Schwitulla, Judith; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; et al. (BREAST, 2018)
PURPOSE: This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). METHODS: The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed. RESULTS: This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern. CONCLUSIONS: This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities.
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Treatment of Early Breast Cancer Patients: Evidence, Controversies, Consensus: Focusing on Systemic Therapy - German Experts' Opinions for the 16th International St. Gallen Consensus Conference (Vienna 2019) - Lüftner, Diana; Bauerfeind, Ingo; Braun, Michael; Brucker, Sara Y.; Fasching, Peter; Felberbaum, Ricardo; Hagemann, Friederike; Haidinger, Renate; Harbeck, Nadia; Hönig, Arnd; Huober, Jens; Jackisch, Christian; et al. (Breast Care, 2019)
A German working group of leading breast cancer experts have discussed the votes at the International St. Gallen Consensus Conference in Vienna for the treatment of primary breast cancer with regard to the German AGO (Ar-beitsgemeinschaft Gynäkologische Onkologie) recommendations for clinical practice in Germany. Three of the German breast cancer experts were also members of this year's St. Gallen panel. Comparing the St. Gallen recommendations with the annually updated treatment recommendations of the Gynecological Oncology Working Group (AGO Mamma 2019) and the German S3 Guideline is useful, because the recommendations of the St. Gallen panel are based on expert opinions of different countries and disciplines. The focus of this article is on systemic therapy. The motto of this year's 16th St. Gallen Consensus Conference was "Estimating the magnitude of clinical benefit." The rationale behind this motto is that, for every treatment decision, a benefit-risk assessment must be taken into consideration for each patient.
CRIS-Team Scopus Importer:2019-10-01

Treatment of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: German Expert Opinions on the 17th International St. Gallen Consensus Conference - Untch, Michael; Fasching, Peter; Brucker, Sara Y.; Budach, Wilfried; Denkert, Carsten; Haidinger, Renate; Huober, Jens; Jackisch, Christian; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Krug, David; Kuehn, Thorsten; et al. (Geburtshilfe und Frauenheilkunde, 2021)
This years 17th St. Gallen (SG) Consensus Conference on the Treatment of Patients with Early Breast Cancer (SG-BCC) with the title "Customizing local and systemic therapies for women with early breast cancer" focused on the challenge of targeting the treatment of early breast cancer more specifically to the individual disease situation of each patient. As in previous years, a German working group of leading breast cancer experts discussed the results of the international SG-BCC 2021 in the context of the German guideline. It is helpful to compare the SG recommendations with the recently updated treatment recommendations of the Breast Commission of the German Working Group on Gynaecological Oncology (Arbeitsgemeinschaft Gynakologische Onkologie e.V., AGO) and the S3 guideline because the SG-BCC panel comprised experts from different countries, which is why country-specific aspects can be incorporated into the SG recommendations. The German treatment recommendations of the AGO and the S3 guideline are based on current evidence. Nevertheless, any therapeutic decision must always undergo a risk-benefit analysis for the specific situation and to be discussed with the patient.
CRIS-Team WoS Importer:2021-06-18

Treatment-related amenorrhea with T-DM1 plus pertuzumab (KP) is lower than with docetaxel/carboplatin/ trastuzumab/pertuzumab (TCHP) in the phase III neoadjuvant KRISTINE trial - Hurvitz, Sara A.; Fresco, Rodrigo; Afenjar, Karen; Stroyakovskiy, Daniil; Huang, Chiun-Sheng; Wildiers, Hans; Jung, Kyung Hae; Boileau, Jean-Francois; Campone, Mario; Martin, Miguel; Valero, Vicente; Sparano, Joseph A.; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Treatment-relevant biomarkers in gynecologic oncology - Ditsch, Nina; Fasching, Peter (Die Gynäkologie, 2022)
The first biomarkers were discovered decades ago. Their prognostic and predictive value is still the subject of current research. Biomarker-based treatments represent the basis of the current and future trial landscape in gynecologic oncology, as was clearly demonstrated at this year's ASCO Annual Meeting. The all-important question is founded in the quality of diagnostics at the immunohistochemical or molecular level. In breast cancer therapy, a HER-2 (human epidermal growth factor receptor 2) finding was previously considered therapeutically relevant if there was an immunohistochemical (IHC) evaluation of 3+ or a fluorescence in situ hybridization (FISH)- or chromogenic in situ hybridization (CISH)-positive value. Use of the antibody-drug conjugate trastuzumab-deruxtecan, also in HER-2-low forms (IHC1+ or 2+, even if FISH/CISH negative), is now celebrated as practice changing, since significantly improved progression-free survival (PFS) and overall survival (OS) were also shown in this situation. With the accelerating use of newer therapeutics, attention should be paid to the side effects and the cost-benefit ratio. The following article provides an overview of the currently most important prognostic and predictive markers in breast, ovarian, endometrial, and cervical cancer.
CRIS-Team WoS Importer:2022-09-09

Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer—findings from the RIBECCA trial - Peuker, Caroline A.; Yaghobramzi, Sarvenaz; Grunert, Corinna; Keilholz, Luisa; Gjerga, Enio; Hennig, Steffen; Schaper, Sigrid; Na, Il Kang; Keller, Ulrich; Brucker, Sara; Decker, Thomas; Fasching, Peter; et al. (European Journal of Cancer, 2022)
Background: Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6i) have significantly improved clinical outcomes in patients with advanced hormone receptor-positive (HR+) breast cancer and have demonstrated favourable antitumour immune responses in preclinical studies. Methods: Here, we investigated peripheral immune responses to ribociclib in patients with metastatic HR+ breast cancer as a preplanned exploratory subanalysis of the RIBECCA trial (NCT03096847). Peripheral blood mononuclear cells were subjected to immune cell profiling, gene expression analysis of immune-related signatures, and deep T cell receptor profiling before treatment started and after 12 weeks of treatment with ribociclib. Results: Gene expression analysis revealed an upregulation of signatures associated with an activated adaptive immune system and a decrease in immunosuppressive cytokine signalling during treatment with ribociclib. Profiling of peripheral immune cell subpopulations showed a decrease in Treg cell frequencies, which was associated with treatment response. Furthermore, induction of CD4+ naive T cells could be seen, whereas effector and memory T cell populations remained largely unchanged. Correspondingly, T cell repertoire diversity remained mostly unchanged during treatment, although an increase in clonality could be observed in single patients. Conclusions: We show that treatment with ribociclib has significant effects on the peripheral innate and adaptive immune response in patients with HR+ breast cancer. Our data suggest that these effects lead to an activation of an already existing immune response rather than a de novo induction and make a strong case for future combination strategies of CDK4/6i with immunotherapies to enhance the adaptive immune response in HR+ breast cancer.
CRIS-Team Scopus Importer:2022-02-11
Keywords: Adaptive immunity; Breast cancer; CDK4/6 inhibitors; Immunomodulation; Ribociclib

Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing - Shimelis, Hermela; Laduca, Holly; Hu, Chunling; Hart, Steven N.; Na, Jie; Thomas, Abigail; Akinhanmi, Margaret; Moore, Raymond M.; Brauch, Hiltrud; Cox, Angela; Eccles, Diana M.; Ewart-Toland, Amanda; et al. (Journal of the National Cancer Institute, 2018)
BACKGROUND: Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor-negative, progesterone receptor-negative, human epidermal growth factor receptor-negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of this study was to define the cancer panel genes associated with increased risk of TNBC. METHODS: Multigene panel testing for 21 genes in 8753 TNBC patients was performed by a clinical testing laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple Negative Breast Cancer Consortium (TNBCC) of research studies. Associations between deleterious mutations in cancer predisposition genes and TNBC were evaluated using results from TNBC patients and reference controls. RESULTS: Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were associated with high risk (odds ratio > 5.0) of TNBC and greater than 20% lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of TNBC. Similar trends were observed for the African American population. Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2) of all participants. CONCLUSIONS: Multigene hereditary cancer panel testing can identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved screening, risk management, and cancer prevention strategies. Patients with mutations may also benefit from specific targeted therapeutic strategies.
EVALuna2:210020

Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2 - Fahlbusch, Fabian B.; Ruebner, Matthias; Hübner, Hanna; Volkert, Gudrun; Bartunik, Hannah; Winterfeld, Ilona; Hartner, Andrea; Menendez-Castro, Carlos; Nögel, Stephanie; Marek, Ines; Wachter, David; Schneider-Stock, Regine; et al. (Histochemistry and Cell Biology, 2015)
Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology.
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Tumor budding: A predictor for metastasis in the CAM xenograft model - Muenzner, Julienne K.; Ranjan, Raphela A.; Eckstein, Markus; Erber, Ramona; Kunze, Philipp; Geppert, Carol-Immanuel; Rübner, Matthias; Bäuerle, Tobias; Hartmann, Arndt; Schneider-Stock, Regine (CANCER RESEARCH, 2019)
CRIS-Team WoS Importer:2019-10-22

Tumor handling of early-stage cervical cancer: A literature analysis of villoglandular adenocarcinoma of the cervix - Dietl, Anna; Aumann, Konrad; Beckmann, Matthias (Anticancer Research, 2020)
Background/Aim: Recent studies have demonstrated the inferior overall survival outcomes of patients with early-stage cervical cancer who undergo minimally invasive surgery (MIS). One possible explanation for these unexpected results is intraoperative tumor manipulation. Materials and Methods: Considering this hypothesis, we have reviewed the literature on the oncological outcomes of patients with villoglandular adenocarcinoma (VGA) of the cervix, an uncommon variant of cervical cancer that has an excellent prognosis. Results: VGA generally presents as an exophytic mass arising from the endocervix. In a systematic review, we identified 221 patients treated surgically for VGA (FIGO stage Ia-Ib1). Of these, 11 developed recurrence, and four died. The recurrence sites in 8 cases were the pelvis (n=3), vaginal cuff (n=3), episiotomy scar (n=1), and cervix (n=1). Furthermore, 23 VGA-patients were treated by MIS, four experienced recurrence, and one died. Three intraabdominal metastases after MIS were reported. Conclusion: Excessive tumor-handling during MIS or manipulations, e.g. cervix-dilation (during delivery), can worsen the otherwise excellent prognosis.
CRIS-Team Scopus Importer:2020-06-19
Keywords: Early-stage cervical cancer; Minimal handling; Minimal invasive surgery; Review; Villoglandular adenocarcinoma of the uterine cervix

Tumor-infiltrating CD8-positive T-lymphocytes in tubo-ovarian high-grade serous cancer are associated with multiple germline variants in 22q12.1 in a genome-wide association analysis - Natanzon, Yanina; Kobel, Martin; Winham, Stacey J.; Armasu, Sebastian M.; Mccauley, Bryan M.; Vierkant, Robert A.; Cunningham, Julie M.; Bowtell, David; Campbell, Ian G.; Chang-Claude, Jenny; Defazio, Anna; Fasching, Peter; et al. (CANCER RESEARCH, 2018)
CRIS-Team WoS Importer:2019-06-18

Tumor-infiltrating lymphocytes and response prediction to neoadjuvant chemotherapy in HER2-positive breast cancer - Heppner, B. Ingold; Untch, M.; Denkert, C.; Pfitzner, B. M.; Lederer, B.; Schmidt, W.; Eidtmann, H.; Fasching, Peter; Tesch, H.; Solbach, C.; Rezai, M.; Zahm, D. -M.; et al. (2016)
EVALuna2:33543

Tumor-Infiltrating Lymphocytes: A Predictive and Prognostic Biomarker in Neoadjuvant-Treated HER2-Positive Breast Cancer - Heppner, Barbara Ingold; Untch, Michael; Denkert, Carsten; Pfitzner, Berit M.; Lederer, Bianca; Schmitt, Wolfgang; Eidtmann, Holger; Fasching, Peter; Tesch, Hans; Solbach, Christine; Rezai, Mahdi; Zahm, Dirk M.; et al. (Clinical Cancer Research, 2016)
PURPOSE: We elucidated the value of tumor-infiltrating lymphocytes (TIL) as an independent predictor for pathologic complete response (pCR) rate and as a prognostic marker for disease-free survival (DFS) in patients with HER2-positive breast cancer in the neoadjuvant setting. EXPERIMENTAL DESIGN: We evaluated stromal TILs in 498 HER2-positive breast cancer samples of the neoadjuvant GeparQuattro (G4) and GeparQuinto (G5) trials. Levels of TILs were determined as a continuous parameter per 10% increase and as lymphocyte-predominant breast cancer (LPBC; ≥ 60% TILs), and correlated with pCR rate and DFS. RESULTS: In the complete cohort, HER2-positive LPBC cases had a significantly increased pCR rates compared with non-LPBC types. They were significant predictors for pCR in univariate (10% TILs: OR 1.12, P = 0.002; LPBC: OR 2.02, P = 0.002) and multivariate analyses (10% TILs: OR 1.1, P = 0.014; LPBC: OR 1.87, P = 0.009). This effect was also detectable in the trastuzumab-treated (10% TILs: OR 1.12, P = 0.018; LPBC: OR 2.08, P = 0.013) but not in the lapatinib-treated subgroup. We identified a low-risk (pCR/LPBC) and a high-risk group (no pCR/no LPBC) regarding DFS. In triple-positive breast cancer, TILs are of more prognostic relevance than pCR. CONCLUSIONS: We could demonstrate the predictive and prognostic impact of TILs in HER2-positive breast cancer in the neoadjuvant setting. In combination with pCR rate, TILs may help to stratify prognostic subgroups, thereby guiding future therapy decisions. Clin Cancer Res; 22(23); 5747-54. ©2016 AACR.
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Tumor mutational burden and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early TNBC in GeparNuevo - Karn, T.; Denkert, C.; Weber, K. E.; Holtrich, U.; Hanusch, C.; Sinn, B. V.; Higgs, B. W.; Jank, P.; Sinn, H. P.; Huober, J.; Becker, C.; Blohmer, J. U.; et al. (Annals of Oncology, 2020)
Background: The predictive value of tumor mutational burden (TMB), alone or in combination with an immune gene expression profile (GEP), for response to neoadjuvant therapy in early triple negative breast cancer (TNBC) is currently not known, either for immune checkpoint blockade (ICB) or conventional chemotherapy. Patients and methods: We obtained both whole exome sequencing and RNA-Seq data from pretreatment samples of 149 TNBC of the recent neoadjuvant ICB trial, GeparNuevo. In a predefined analysis, we assessed the predictive value of TMB and a previously developed immune GEP for pathological complete remission (pCR). Results: Median TMB was 1.52 mut/Mb (range 0.02–7.65) and was significantly higher in patients with pCR (median 1.87 versus 1.39; P = 0.005). In multivariate analysis, odds ratios for pCR per mut/Mb were 2.06 [95% confidence intervals (CI) 1.33–3.20, P = 0.001] among all patients, 1.77 (95% CI 1.00–3.13, P = 0.049) in the durvalumab treatment arm, and 2.82 (95% CI 1.21–6.54, P = 0.016) in the placebo treatment arm, respectively. We also found that both continuous TMB and immune GEP (or tumor infiltrating lymphocytes) independently predicted pCR. When we stratified patients in groups based on the upper tertile of TMB and median GEP, we observed a pCR rate of 82% (95% CI 60% to 95%) in the group with both high TMB and GEP in contrast to only 28% (95% CI 16% to 43%) in the group with both low TMB and GEP. Conclusions: TMB and immune GEP add independent value for pCR prediction. Our results recommend further analysis of TMB in combination with immune parameters to individually tailor therapies in breast cancer.
CRIS-Team Scopus Importer:2020-07-10
Keywords: exome sequencing; neoadjuvant immune checkpoint inhibition; triple negative breast cancer; tumor mutational burden

Tumor–Stroma Ratio in Colorectal Cancer—Comparison between Human Estimation and Automated Assessment - Firmbach, Daniel; Benz, Michaela; Kuritcyn, Petr; Bruns, Volker; Lang-Schwarz, Corinna; Stübs, Frederik; Merkel, Susanne; Leikauf, Leah-Sophie; Braunschweig, Anna Lea; Oldenburger, Angelika; Gloßner, Laura; Abele, Niklas; et al. (Cancers, 2023)
The tumor–stroma ratio (TSR) has been repeatedly shown to be a prognostic factor for survival prediction of different cancer types. However, an objective and reliable determination of the tumor–stroma ratio remains challenging. We present an easily adaptable deep learning model for accurately segmenting tumor regions in hematoxylin and eosin (H&E)-stained whole slide images (WSIs) of colon cancer patients into five distinct classes (tumor, stroma, necrosis, mucus, and background). The tumor–stroma ratio can be determined in the presence of necrotic or mucinous areas. We employ a few-shot model, eventually aiming for the easy adaptability of our approach to related segmentation tasks or other primaries, and compare the results to a well-established state-of-the art approach (U-Net). Both models achieve similar results with an overall accuracy of 86.5% and 86.7%, respectively, indicating that the adaptability does not lead to a significant decrease in accuracy. Moreover, we comprehensively compare with TSR estimates of human observers and examine in detail discrepancies and inter-rater reliability. Adding a second survey for segmentation quality on top of a first survey for TSR estimation, we found that TSR estimations of human observers are not as reliable a ground truth as previously thought.
CRIS-Team Scopus Importer:2023-06-09
Keywords: colorectal cancer; deep learning; few-shot learning; image analysis; segmentation; tumor–stroma ratio; U-Net

Tumour-infiltrating inflammatory cells in early breast cancer: An underrated prognostic and predictive factor? - Schnellhardt, Sören; Erber, Ramona; Büttner-Herold, Maike; Rosahl, Marie Charlotte; Ott, Oliver; Strnad, Vratislav; Beckmann, Matthias; King, Lillian; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold (International Journal of Molecular Sciences, 2020)
The role of tumour-infiltrating inflammatory cells (TIICs) in the disease progression of hormone-receptor-positive breast cancer (HR+ BC) is largely unclear since it is generally regarded as the least immunogenic BC subtype. This study investigated the prognostic significance of CD1a+ dendritic cells, CD20+ B cells, CD45RO+ memory T cells and CD4+ T-helper cells in HR+ BC. One hundred and forty-six patients were treated for early stage, distant-metastases-free HR+ BC in an accelerated partial breast irradiation (APBI) phase II trial. Immunohistochemistry was used to double-stain two adjoining sets of tissue microarrays from pre-RT (radiotherapy) tumour resection samples for CD1a/CD20 and CD45RO/CD4. Cell densities of CD1a+, CD20+, CD45RO+ and CD4+ TIICs in the stromal and intraepithelial compartment were registered semiautomatically. High densities of CD20+ and CD4+ TIICs were strongly associated with reduced disease-free survival (DFS), while high stromal CD45RO+ TIIC densities were indicators of subsequent successful treatment. An immunoscore based on CD20+ and CD45RO+ TIIC densities identified three different risk groups (p < 0.001). Thus, contrary to current assumptions, intratumoural immune cell composition might be an important prognostic indicator and a possible contributing factor in the outcome of HR+ BC and should be the subject of further research. Specifically, B-cell infiltration entailed an increased relapse rate and could play an important role in disease progression.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Accelerated partial breast irradiation; Breast cancer; CD1a; CD20; CD4; CD45RO; Hormone receptor positive; Immunoscore; Prognosis; TIL

Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy - Denkert, Carsten; Von Minckwitz, Gunter; Darb-Esfahani, Silvia; Lederer, Bianca; Heppner, Barbara I.; Weber, Karsten E.; Budczies, Jan; Huober, Jens; Klauschen, Frederick; Furlanetto, Jenny; Schmitt, Wolfgang D.; Blohmer, Jens-Uwe; et al. (Lancet Oncology, 2018)
BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are predictive for response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, but their role in luminal breast cancer and the effect of TILs on prognosis in all subtypes is less clear. Here, we assessed the relevance of TILs for chemotherapy response and prognosis in patients with TNBC, HER2-positive breast cancer, and luminal-HER2-negative breast cancer. METHODS: Patients with primary breast cancer who were treated with neoadjuvant combination chemotherapy were included from six randomised trials done by the German Breast Cancer Group. Pretherapeutic core biopsies from 3771 patients included in these studies were assessed for the number of stromal TILs by standardised methods according to the guidelines of the International TIL working group. TILs were analysed both as a continuous parameter and in three predefined groups of low (0-10% immune cells in stromal tissue within the tumour), intermediate (11-59%), and high TILs (≥60%). We used these data in univariable and multivariable statistical models to assess the association between TIL concentration and pathological complete response in all patients, and between the amount of TILs and disease-free survival and overall survival in 2560 patients from five of the six clinical trial cohorts. FINDINGS: In the luminal-HER2-negative breast cancer subtype, a pathological complete response (pCR) was achieved in 45 (6%) of 759 patients with low TILs, 48 (11%) of 435 with intermediate TILs, and 49 (28%) of 172 with high TILs. In the HER2-positive subtype, pCR was observed in 194 (32%) of 605 patients with low TILs, 198 (39%) of 512 with intermediate TILs, and 127 (48%) of 262 with high TILs. Finally, in the TNBC subtype, pCR was achieved in 80 (31%) of 260 patients with low TILs, 117 (31%) of 373 with intermediate TILs, and 136 (50%) of 273 with high TILs (p<0·0001 for each subtype, χ2 test for trend). In the univariable analysis, a 10% increase in TILs was associated with longer disease-free survival in TNBC (hazard ratio [HR] 0·93 [95% CI 0·87-0·98], p=0·011) and HER2-positive breast cancer (0·94 [0·89-0·99], p=0·017), but not in luminal-HER2-negative tumours (1·02 [0·96-1·09], p=0·46). The increase in TILs was also associated with longer overall survival in TNBC (0·92 [0·86-0·99], p=0·032), but had no association in HER2-positive breast cancer (0·94 [0·86-1·02], p=0·11), and was associated with shorter overall survival in luminal-HER2-negative tumours (1·10 [1·02-1·19], p=0·011). INTERPRETATION: Increased TIL concentration predicted response to neoadjuvant chemotherapy in all molecular subtypes assessed, and was also associated with a survival benefit in HER2-positive breast cancer and TNBC. By contrast, increased TILs were an adverse prognostic factor for survival in luminal-HER2-negative breast cancer, suggesting a different biology of the immunological infiltrate in this subtype. Our data support the hypothesis that breast cancer is immunogenic and might be targetable by immune-modulating therapies. In light of the results in luminal breast cancer, further research investigating the interaction of the immune system with different types of endocrine therapy is warranted. FUNDING: Deutsche Krebshilfe and European Commission.
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Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011 - Schoffer, Olaf; Schuelein, Stefanie; Arand, Gerlinde; Arnholdt, Hans; Baaske, Dieter; Bargou, Ralf C.; Becker, Nikolaus; Beckmann, Matthias; Bodack, Yves; Boehme, Beatrix; Bozkurt, Tayfun; Breitsprecher, Regine; et al. (BMC Cancer, 2016)
Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival.The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97-0.97), sex (OR 1.18, 95% CI 1.11-1.25), date of diagnosis (OR 1.05, 95% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95% CI 2.50-4.19) and place of residence (OR 1.23, 95% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8-83.9%).No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.
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Twenty-five-year-old Woman with Bilateral Borderline Ovarian Tumour Desiring to Preserve Fertility - Case Report and Literature Review on the Current State of Fertility Preservation in Women with Borderline Ovarian Tumours - Findeklee, S.; Lotz, Laura; Heusinger, K.; Hoffmann, Inge; Dittrich, Ralf; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2016)
Borderline ovarian tumours are semimalignant tumours occurring unilaterally or bilaterally with a peak incidence among women of reproductive age. Since the affected women often wish to preserve fertility, particular precautions must be taken when counselling the patient and obtaining consent prior to planning an individual treatment. Options for preserving fertility include an organ-sparing surgical procedure and cryopreservation of oocytes and/or ovarian tissue. In this article, we report on a 25-year-old patient with a bilateral seromucinous borderline tumour who desired all fertility-preserving options. In order to perform the procedure without delay, we opted to perform luteal phase stimulation prior to oocyte retrieval. We conclude by discussing the current literature on the state of fertility preservation in the treatment of borderline ovarian tumours.
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Two truncating variants in FANCC and breast cancer risk - Dork, Thilo; Peterlongo, Paolo; Mannermaa, Arto; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Ahearn, Thomas; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Aronson, Kristan J.; Augustinsson, Annelie; et al. (Scientific Reports, 2019)
Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
CRIS-Team Scopus Importer:2019-09-17

Ultrasound Elastography of Pulmonary Lesions - A Feasibility Study - Adamietz, B. R.; Fasching, Peter; Jud, Sebastian; Schulz-Wendtland, Rüdiger; Anders, Katharina; Uder, Michael; Wüst, Wolfgang; Rauh, C.; Meier-Meitinger, M. (Ultraschall in der Medizin, 2014)
Introduction: The potential of sonography in the examination of lung tissue is extremely limited by the air-filled alveoles of the lung. Only in special circumstances like pleural adhesion lesions, atelectasis or pneumonia can lung tissue be visualized by B-mode sonography. Real-time elastography was primarily applied to detect and visualize pulmonary lesions. Methods and Patients: 8 patients with a total of 18 histologically proven metastases of the lung were included. All pulmonary lesions were detected by computed tomography. Sonographic examination was performed with a 7.5 MHz linear transducer (Acuson Antares premium edition, Siemens, Erlangen, Germany), including B-mode and real-time elastography (RTE). The mean distance between pleura and the lesions ranged from 0 to 2.5 cm. Two lesions were located in the upper right lobe, eleven lesions in the lower right and five in the lower left lobe. Results: RTE was able to detect and visualize all 18 pulmonary lesions in contrast to B-mode. The size and distance of the lesions from the pleura correlated with the CT findings. Conclusion: In contrast to B-mode sonography, RTE is able to detect and visualize peripheral, non-pleural adherent pulmonary lesions.
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Ultrasound Fetal Weight Estimation in Diabetic Pregnancies - Pretscher, Jutta; Kehl, Sven; Stumpfe, Florian M.; Mayr, Andreas; Schmid, Matthias; Schild, Ralf L.; Beckmann, Matthias; Faschingbauer, Florian (Journal of Ultrasound in Medicine, 2019)
Objectives To evaluate different formulas for estimating fetal weight in diabetic pregnancies. Methods This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight. Results Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small. Conclusions Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range.
CRIS-Team WoS Importer:2019-09-13

Ultrasound Fetal Weight Estimation in Diabetic Pregnancies - Pretscher, Jutta; Kehl, Sven; Stumpfe, Florian M.; Mayr, Andreas; Schmid, Matthias; Schild, Ralf L.; Beckmann, Matthias; Faschingbauer, Florian (Journal of Ultrasound in Medicine, 2020)
OBJECTIVES: To evaluate different formulas for estimating fetal weight in diabetic pregnancies. METHODS: This retrospective study evaluated the precision of ultrasound fetal weight estimation in 756 pregnancies complicated by gestational diabetes between 2002 and 2016. The estimated fetal weights (EFWs) were obtained within 7 days of delivery from 10 weight estimation formulas and were compared with pair-wise matched controls from 15,701 patients. The precision of the evaluated formulas for EFW was analyzed by median absolute percentage errors (MAPEs), mean percentage errors (MPEs), and proportions of estimates within 10% of actual birth weight. RESULTS: Among the tested formulas, the lowest MAPE was detected with formula I of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337), and the formula of Schild et al (Ultrasound Obstet Gynecol 2004; 23:30-35) had the highest proportion of estimates within the 10% range. The EFW in diabetic patients showed a slight trend toward overestimation in comparison with the matched controls (MPE estimates showed a trend toward more positive values). In most of the EFW formulas that were evaluated, no significant differences were detected in MAPEs and estimates within the 10% range. The MPE estimates with most formulas in both groups were close to zero. Overall, the differences between most of the evaluated formulas were small. CONCLUSIONS: Little evidence was found for differences in the accuracy of the EFW in diabetic pregnancies and controls. The Hadlock I formula showed the lowest MAPE, and the Schild formula had the highest proportion of estimates within the 10% range.
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Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer - Heger, Lukas; Heidkamp, Gordon Frederik; Amon, Lukas; Nimmerjahn, Falk; Bäuerle, Tobias; Maier, Andreas; Erber, Ramona; Hartmann, Arndt; Hack, Carolin; Rübner, Matthias; Hübner, Hanna; Fasching, Peter; et al. (OncoImmunology, 2024)
Breast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype of breast cancer. However, it is still not clear which patients benefit from immunotherapeutic approaches such as checkpoint blockade. Thus, we aimed to decipher the immune cell signature of the different breast cancer subtypes based on high-dimensional flow cytometry followed by unbiased approaches. Here, we show that the frequency of NK cells is reduced in Luminal A and B as well as triple negative breast cancer and that the phenotype of residual NK cells is changed toward regulatory CD11b−CD16− NK cells. Further, we found higher frequencies of PD-1+ CD4+ and CD8+ T cells in triple negative breast cancer. Moreover, while Luminal A-type breast cancer was enriched for CD14+ cDC2 (named type 3 DC (DC3)), CD14− cDC2 (named DC2) were more frequent in triple negative breast cancer. In contrast, HER2-enriched breast cancer did not show major alterations in the composition of the immune cell compartment in the tumor microenvironment. These findings suggest that patients with Luminal A- and B-type as well as triple negative breast cancer might benefit from immunotherapeutic approaches targeting NK cells.
CRIS-Team Scopus Importer:2024-01-12
Keywords: Breast cancer; immune cell signature; NK cells; PD-1; tumor microenvironment

Unexpected diagnose of endometriosis in women undergoing ovarian tissue transplantation - Lotz, Laura; Dietl, Anna; Hoffmann, Inge; Mueller, A.; Burghaus, Stefanie; Beckmann, Matthias; Dittrich, Ralf (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Update Breast Cancer 2017 - Implementation of Novel Therapies - Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Huober, Jens B.; Lueftner, Diana; et al. (Geburtshilfe und Frauenheilkunde, 2017)
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.
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Update Breast Cancer 2018 (Part 1) - Primary Breast Cancer and Biomarkers - Taran, Florin-Andrei; Schneeweiss, Andreas; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Woeckel, Achim; Ettl, Johannes; et al. (Geburtshilfe und Frauenheilkunde, 2018)
This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.
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Update Breast Cancer 2018 (Part 2) - Advanced Breast Cancer, Quality of Life and Prevention - Schneeweiss, Andreas; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Woeckel, Achim; Ettl, Johannes; et al. (Geburtshilfe und Frauenheilkunde, 2018)
The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented.
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Update Breast Cancer 2018 (Part 3) - Genomics, Individualized Medicine and Immune Therapies - in the Middle of a New Era: Prevention and Treatment Strategies for Early Breast Cancer - Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Overkamp, Friedrich; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Lueftner, Diana; Mueller, Volkmar; et al. (Geburtshilfe und Frauenheilkunde, 2018)
In primary early breast cancer, the aim of treatment planning is to obtain an increasingly better understanding of the disease. The identification of patients with an excellent prognosis could help this group avoid unnecessary treatments. Furthermore, the planning of treatment is becoming increasingly patient-focussed. There is a growing understanding of those patients who benefit particularly from chemotherapy, as well as of those who could benefit from immunotherapy. Studies conducted on immunotherapies will be published shortly. Smaller individual studies offer an initial insight into the efficacy of checkpoint inhibitors (anti-PD1/PDL1 therapies). Not least, one of the largest breast cancer studies of all times has recently come to an end. The use of a multigene test has shown that it is sufficient to identify patients with such a good prognosis that chemotherapy is unnecessary. This review article is intended to summarise the current studies and give an outlook on current developments.
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Update Breast Cancer 2018 (Part 4) - Genomics, Individualized Medicine and Immune Therapies - in the Middle of a New Era: Treatment Strategies for Advanced Breast Cancer - Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Lueftner, Diana; Welslau, Manfred; et al. (Geburtshilfe und Frauenheilkunde, 2018)
New therapeutic developments aimed at treating women with advanced breast cancer currently focus both on identifying patients eligible for targeted therapeutic concepts and on the continuing development of immune therapies. The data on CDK4/6 inhibitors are now complete and consistent in this class of substances (palbociclib, ribociclib and abemaciclib). Further pathways under investigation are PI3K and AKT signalling pathways along with diverse approaches to their inhibition. Initial study results were also presented recently on both mechanisms of action. Insights into the PARP inhibitors, moreover, are increasing; studies in this respect are also examining in which population they can be used most effectively. This review offers a summary of the recent studies and an outline of the latest developments.
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Update Breast Cancer 2019 Part 1-Implementation of Study Results of Novel Study Designs in Clinical Practice in Patients with Early Breast Cancer - Hartkopf, Andreas D.; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Nabieva, Naiba; Taran, Florin-Andrei; Ettl, Johannes; Lueftner, Diana; Belleville, Erik; Schuetz, Florian; Fasching, Peter; et al. (Geburtshilfe und Frauenheilkunde, 2019)
For many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called post-neoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.
CRIS-Team WoS Importer:2019-04-02

Update Breast Cancer 2019 Part 2-Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice - Janni, Wolfgang; Schneeweiss, Andreas; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin-Andrei; Tesch, Hans; Overkamp, Friedrich; Lueftner, Diana; Belleville, Erik; et al. (Geburtshilfe und Frauenheilkunde, 2019)
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 addition-al markers within subgroups in order to predict the efficacy of a therapy. PI3K mutation testing in HER2-negative, hormonereceptor- 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 patients ' 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.
CRIS-Team WoS Importer:2019-04-02

Update Breast Cancer 2019 Part 2 - Implementation of Novel Diagnostics and Therapeutics in Advanced Breast Cancer Patients in Clinical Practice Update Mammakarzinom 2019 Teil 2 - Implementierung neuer Diagnostika und Therapien bei Patientinnen mit fortgeschrittenem Brustkrebs in der klinischen Praxis - Janni, Wolfgang; Schneeweiss, Andreas; Müller, Volkmar; Wöckel, Achim; Lux, Michael P.; Hartkopf, Andreas D.; Nabieva, Naiba; Taran, Florin Andrei; Tesch, Hans; Overkamp, Friedrich; Lüftner, Diana; Belleville, Erik; et al. (TumorDiagnostik & Therapie, 2019)
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, hormonereceptor-positive tumours and PDâ€ 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 patientsÊ¼ 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.
CRIS-Team Scopus Importer:2019-09-17
Keywords: advanced; alpelisib; atezolizumab; breast cancer; metastatic; PARP; PD-L1; PI3K; supportive therapy

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel - Kolberg, Hans Christian; Schneeweiss, Andreas; Fehm, Tanja N.; Wöckel, Achim; Huober, Jens; Pontones, Constanza; Titzmann, Adriana; Belleville, Erik; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Taran, Florin Andrei; et al. (Geburtshilfe und Frauenheilkunde, 2019)
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.
CRIS-Team Scopus Importer:2019-06-04
Keywords: adjuvant therapy; early breast cancer; neoadjuvant therapy; St. Gallen panel of experts

Update Breast Cancer 2019 Part 3 - Current Developments in Early Breast Cancer: Review and Critical Assessment by an International Expert Panel Update Mammakarzinom 2019 Teil 3 - aktuelle Entwicklungen bei der kurativen Behandlung von Mammakarzinom-Patientinnen: Eine Übersicht und Bewertung durch ein internationales Expertenpanel - Kolberg, Hans Christian; Schneeweiss, Andreas; Fehm, Tanja N.; Wöckel, Achim; Huober, Jens; Pontones, Constanza; Titzmann, Adriana; Belleville, Erik; Lux, Michael P.; Janni, Wolfgang; Hartkopf, Andreas D.; Taran, Florin Andrei; et al. (TumorDiagnostik & Therapie, 2019)
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.
CRIS-Team Scopus Importer:2019-09-17
Keywords: adjuvant therapy; early breast cancer; neoadjuvant therapy; St. Gallen panel of experts

Update Breast Cancer 2019 Part 4 – Diagnostic and Therapeutic Challenges of New, Personalised Therapies for Patients with Early Breast Cancer - Schütz, Florian; Fasching, Peter; Welslau, Manfred; Hartkopf, Andreas D.; Wöckel, Achim; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Lüftner, Diana; Belleville, Erik; Kolberg, Hans Christian; Overkamp, Friedrich; et al. (Geburtshilfe und Frauenheilkunde, 2019)
The further development of therapies for women with early breast cancer is progressing far more slowly than in the case of patients with advanced breast cancer and is additionally delayed compared to developments in metastatic breast cancer. Nonetheless, significant advancements have been able to be recorded recently. This review summarises the latest developments in view of the most recent publications and professional conferences. For hormone-receptor-positive patients, new aspects for the duration of antihormone therapy and with regard to the benefits of multigene tests have been published. In the case of HER2-positive patients, the value of post-neoadjuvant therapy and de-escalation of the therapy is discussed. In patients with triple-negative breast cancer, there is a question of whether the knowledge of the biological background of a homologous recombination deficiency (HRD) helps develop new therapies for this subtype. In particular the use of a BRCA1/2 mutation or the biological characteristic HRD as a potential motive for therapy plays a role here in specifying the significance of platinum therapy and therapy with PARP inhibitors.
CRIS-Team Scopus Importer:2019-11-05
Keywords: adjuvant; antihormone therapy; breast cancer; chemotherapy; multigene tests; neoadjuvant

Update Breast Cancer 2019 Part 5 - Diagnostic and Therapeutic Challenges of New, Personalised Therapies in Patients with Advanced Breast Cancer. - Welslau, Manfred; Hartkopf, Andreas D.; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Lueftner, Diana; Belleville, Erik; Schuetz, Florian; Fasching, Peter; Kolberg, Hans-Christian; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Significant advancements have been made in recent years in advanced breast cancer and nearly all of them have been in the field of targeted therapy. Pertuzumab and trastuzumab-emtansine (T-DM1) have been able to be introduced in HER2-positive breast cancer. Now other anti-HER2 therapies are being developed (e.g. margetuximab, DS-8201a, pyrotinib) which can overcome other resistance mechanisms in the HER2 signalling pathway. In the field of hormone-receptor-positive breast cancer, an mTOR inhibitor and CDK4/6 inhibitors were introduced in the past. Now the introduction of the first PI3K inhibitor is forthcoming and this inhibitor will involve genetic testing of the tumour for a mutation in the PIK3CA gene. There are also significant advancements in triple-negative breast cancer: By combining chemotherapy and immunotherapy, an advantage for overall survival was able to be demonstrated in a subgroup (immune cells PD-L1-positive). The PARP inhibitor therapy for HER2-negative patients with a germ line mutation in BRCA1 or BRCA2 was also associated with an improved overall survival in a subgroup. These promising new study results are summarised in this review.
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Update Breast Cancer 2020 Part 1 – Early Breast Cancer: Consolidation of Knowledge About Known Therapies - Schneeweiss, Andreas; Hartkopf, Andreas D.; Mueller, Volkmar; Woeckel, Achim; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Huober, Jens; Thill, Marc; Fasching, Peter; Kolberg, Hans-Christian; et al. (Geburtshilfe und Frauenheilkunde, 2020)
This review is intended to present the latest developments in the prevention and treatment of early breast cancer. The risk of breast cancer can be increasingly better characterised with large epidemiological studies on genetic and non-genetic risk factors. Through new analyses, the evidence for high-penetrance genes as well as for low-penetrance genes was able to be improved. New data on denosumab and atezolizumab are available in the neoadjuvant situation as is a pooled appraisal of numerous studies on capecitabine in the curative situation. There is also an update to the overall survival data of pertuzumab in the adjuvant situation with a longer follow-up observation period. Finally, digital medicine is steadily finding its way into science. A recently conducted study on automated breast cancer detection using artificial intelligence establishes the basis for a future review in clinical studies.
CRIS-Team Scopus Importer:2020-03-27
Keywords: digital medicine; early breast cancer; immune therapy; prevention; prognosis; therapy

Update Breast Cancer 2020 Part 2 - Advanced Breast Cancer: New Treatments and Implementation of Therapies with Companion Diagnostics - Lüftner, Diana; Schneeweiss, Andreas; Hartkopf, Andreas D.; Müller, Volkmar; Wöckel, Achim; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Schütz, Florian; Thill, Marc; Huober, Jens; Fasching, Peter; et al. (Geburtshilfe und Frauenheilkunde, 2020)
For patients with locally advanced or metastatic breast cancer, new and effective therapies such as CDK4/6 inhibitors, PARP inhibitors and a PD-L1 inhibitor have been introduced in recent years. This review presents an update on the available studies with their data. In addition, two innovative anti-HER2 therapies are presented (trastuzumab-deruxtecan and tucatinib) for which the results from new studies have been reported. Molecular tests offer the possibility of defining patient populations or also monitoring courses of therapy. This can help identify patients with specific characteristics in order to provide them with individually targeted therapy within the framework of studies. In a large study, the benefit of such a biomarker study was able to be described for the first time.
CRIS-Team Scopus Importer:2020-05-15
Keywords: advanced breast cancer; BRCA1/2; CDK4/6; immune therapy; metastases; mutational testing; PARP; PD-L1; therapy

Update Breast Cancer 2020 Part 3 - Early Breast Cancer - Huober, Jens; Schneeweiss, Andreas; Hartkopf, Andreas D.; Müller, Volkmar; Lux, Michael P.; Janni, Wolfgang; Ettl, Johannes; Belleville, Erik; Thill, Marc; Fasching, Peter; Kolberg, Hans Christian; Schulmeyer, Carla; et al. (Geburtshilfe und Frauenheilkunde, 2020)
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.
CRIS-Team Scopus Importer:2020-11-27
Keywords: digital medicine; early breast cancer; immunotherapy; prevention; prognosis; treatment

Update Breast Cancer 2020 Part 4 – Advanced Breast Cancer - Tesch, Hans; Müller, Volkmar; Wöckel, Achim; Ettl, Johannes; Belleville, Erik; Schütz, Florian; Hartkopf, Andreas; Thill, Marc; Huober, Jens; Fasching, Peter; Kolberg, Hans Christian; Schulmeyer, Carla E.; et al. (Geburtshilfe und Frauenheilkunde, 2020)
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.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Advanced breast cancer; BRCA1/2; CDK4/6; immunotherapy; metastases; mutation testing; PARP; PD-L1; treatment

Update Breast Cancer 2020 Part 5 - Moving Therapies from Advanced to Early Breast Cancer Patients - Lux, Michael P.; Schneeweiss, Andreas; Hartkopf, Andreas D.; Müller, Volkmar; Janni, Wolfgang; Belleville, Erik; Stickeler, Elmar; Thill, Marc; Fasching, Peter; Kolberg, Hans Christian; Untch, Michael; Harbeck, Nadia; et al. (Geburtshilfe und Frauenheilkunde, 2021)
In recent years, significant progress has been made in new therapeutic approaches to breast cancer, particularly in patients with HER2-positive and HER2-negative/hormone receptor-positive (HR+) breast cancer. In the case of HER2-positive tumours, these approaches have included, in particular, treatment with pertuzumab, T-DM1, neratinib and, soon, also tucatinib and trastuzumab deruxtecan (neither of which has yet been authorised in Europe). In patients with HER2-/HR+ breast cancer, CDK4/6 inhibitors and the PIK3CA inhibitor alpelisib are of particular importance. Further novel therapies, such as Akt kinase inhibitors and oral SERDs (selective estrogen receptor down regulators), are already being investigated in ongoing clinical trials. These therapeutic agents are not only being introduced into curative, (neo-)adjuvant therapeutic settings for HER2-positive tumours; a first favourable study on abemaciclib as an adjuvant therapy has now also been published. In patients with triple-negative breast cancer, after many years of negative study results with the Trop-2 antibody drug conjugate (ADC) sacituzumab govitecan, a randomised study has been published that may represent a significant therapeutic advance. This review describes the latest developments in breast cancer subsequent to the ESMO Congress 2020.
CRIS-Team Scopus Importer:2021-05-21
Keywords: digital medicine; early breast cancer; immune therapy; prognosis; therapy

Update Breast Cancer 2021 Part 1-Prevention and Early Stages - Stickeler, Elmar; Aktas, Bahriye; Behrens, Annika; Belleville, Erik; Ditsch, Nina; Fasching, Peter; Fehm, Tanja N.; Hartkopf, Andreas D.; Jackisch, Christian; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Kolberg, Hans-Christian; et al. (Geburtshilfe und Frauenheilkunde, 2021)
This review summarises not only the latest evidence on prevention, but also the current research on the treatment of early-stage breast cancer patients. Recent years have seen a growing body of evidence on the risk of high- and moderate-penetrance breast cancer susceptibility genes. A large international consortium has now been able to further refine the answer to the question of the significance of the so-called panel genes. Moreover, the data on treatment selection regarding endocrine efficacy and the decision for or against chemotherapy have also been advanced markedly. There is also new data on adjuvant CDK4/6 (cyclin-dependent kinase 4/6) inhibitors, which are standard in first-line treatment in patients with metastatic HER2-negative, hormone receptor-positive (HR+) breast cancer. For other therapies such as immune checkpoint inhibitors, which have successfully improved the rate of pathologic complete response (pCR) in neoadjuvant treatment settings for patients with triple-negative breast cancer (TNBC), there is a growing understanding of the quality of life and side effects. This is especially important in situations where patients could possibly be cured without such a regimen.
CRIS-Team WoS Importer:2021-05-21

Update Breast Cancer 2021 Part 2-Advanced Stages, Long-Term Consequences and Biomarkers - Ditsch, Nina; Stickeler, Elmar; Behrens, Annika; Belleville, Erik; Fasching, Peter; Fehm, Tanja N.; Hartkopf, Andreas D.; Jackisch, Christian; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Kolberg, Hans-Christian; Lueftner, Diana; et al. (Geburtshilfe und Frauenheilkunde, 2021)
This review summarises and discusses significant aspects of recently published studies on patient treatment in advanced breast cancer and on biomarkers in breast cancer. In recent years, a large number of drugs for all molecular subtypes have been developed up to phase III trials. With regard to immune checkpoint inhibitors in metastasised breast cancer, the recent discussion has centred on the best candidate for combined chemotherapy. The oral taxanes could become a new type of oral chemotherapies. There is a growing body of data on biomarkers for the use of CDK4/6 inhibitors, which could also signify further development for other molecular subtypes. New substances have been developed for metastatic HER2+ breast cancer that still result in good remission even after massive prior treatment and/or cerebral metastasis. Similarly, knowledge is growing about targeted therapies with antibody-drug conjugates (ADC) against Trop-2, which could bolster our therapeutic armoury in triple-negative breast cancer (TNBC). In addition, the clinical focus is on understanding how to maintain fertility after breast cancer treatment. Here, pooled analyses provide new insights.
CRIS-Team WoS Importer:2021-05-21

Update Breast Cancer 2021 Part 3 – Current Developments in the Treatment of Early Breast Cancer: Review and Assessment of Specialised Treatment Scenarios by an International Expert Panel - Fehm, Tanja N.; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Kolberg, Hans Christian; Lüftner, Diana; Müller, Volkmar; Schütz, Florian; Thomssen, Christoph; Belleville, Erik; Behrens, Annika; et al. (Geburtshilfe und Frauenheilkunde, 2021)
The continuous availability of findings from new studies repeatedly results in updated treatment recommendations and guidelines. In the case of breast carcinoma in particular, several studies have been published in the last few years that have transformed how early and advanced breast carcinoma is being treated. However, this by no means means implies that there is agreement among all experts on specific issues. It is precisely the diversity of interpretation of guidelines and study findings that reflects the constantly changing available data and its complexity, as well as the availability of new drugs. In recent years, new substances such as pertuzumab, T-DM1, neratinib and capecitabine have become available to treat patients with early stages of breast carcinoma. Furthermore, the first results on the use of CDK4/6 inhibitors for adjuvant treatment have now been published. Last but not least, the use of multigene tests to avoid the necessity of chemotherapy in certain patients is still under discussion. This review summarises the state of the data and publishes the results of the survey completed by experts at the 2021 St. Gallen Breast Cancer Conference on early-stage breast cancer.
CRIS-Team Scopus Importer:2021-07-02
Keywords: early breast cancer; expert panel; therapy decisions

Update Breast Cancer 2021 Part 4 - Prevention and Early Stages. - Thomssen, Christoph; Fehm, Tanja N.; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Kolberg, Hans-Christian; Lueftner, Diana; Mueller, Volkmar; Schuetz, Florian; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
This past year has seen new and effective options for further improving treatment outcome in many patients with early-stage breast cancer. Patients with hormone receptor-positive disease benefited significantly from the addition of the CDK4/6 inhibitor abemaciclib to endocrine adjuvant therapy. In triple-negative disease, data were presented for two treatment regimens. Patients with advanced disease (stage 2 and 3) benefit from neoadjuvant treatment with the immune checkpoint inhibitor pembrolizumab in combination with standard chemotherapy, regardless of PD-L1 expression. When neoadjuvant therapy has failed to achieve the desired remission in BRCA1 and BRCA2 mutations, the administration of the PARP inhibitor olaparib has demonstrated an impressive response. Other data address translational issues in HER2-positive breast cancer and neoadjuvant therapy approaches with the oral SERD giredestrant and the PARP inhibitor talazoparib. This review presents and analyses the findings of this year' s most important study outcomes.
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Keywords: BRCA (breast cancer associated gene); breast; genetics; Her-2/neu (human epidermal growth factor receptor); hormonal receptor; breast cancer

Update Breast Cancer 2021 Part 5 - Advanced Breast Cancer. - Lueftner, Diana; Schuetz, Florian; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Kolberg-Liedtke, Cornelia; Kolberg, Hans-Christian; Thomssen, Christoph; Mueller, Volkmar; Fehm, Tanja N.; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Despite the COVID 19 pandemic and mostly virtual congresses, innovation in the treatment of breast cancer patients continues at an unabated pace. This review summarises the current developments. Initial overall survival data for CDK4/6 inhibitor treatment in combination with an aromatase inhibitor as the first advanced line of therapy in treatment-naive postmenopausal patients have been published. Similarly, a trial comparing trastuzumab-deruxtecan versus trastuzumab-emtansine revealed a clear benefit regarding progression-free survival. Understanding of biomarkers making checkpoint inhibitor therapy particularly effective is increasing, and new compounds such as oral selective estrogen receptor destabilisers (SERDs) are entering clinical development and completing the first phase III trials.
EVALuna2:506657

Update Breast Cancer 2022 Part 1 - Early Stage Breast Cancer. - Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Fehm, Tanja N.; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Evidence relating to the treatment of breast cancer patients with early-stage disease has increased significantly in the past year. Abemaciclib, olaparib, and pembrolizumab are new drugs with good efficacy in the relevant patient groups. However, some questions remain unanswered. In particular, it remains unclear which premenopausal patients with hormone receptor-positive breast cancer should be spared unnecessary treatment. The question of the degree to which chemotherapy exerts a direct cytotoxic effect on the tumor or reduces ovarian function through chemotherapy could be of key importance. This group of patients could potentially be spared chemotherapy. New, previously experimental biomarker analysis methods, such as spatial analysis of gene expression (spatial transcriptomics) are gradually finding their way into large randomized phase III trials, such as the NeoTRIP trial. This in turn leads to a better understanding of the predictive factors of new therapies, for example immunotherapy. This review summarizes the scientific innovations from recent congresses such as the San Antonio Breast Cancer Symposium 2021 but also from recent publications.
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Update Breast Cancer 2022 Part 2 - Advanced Stage Breast Cancer - Müller, Volkmar; Welslau, Manfred; Lüftner, Diana; Schütz, Florian; Stickeler, Elmar; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Fehm, Tanja N.; Belleville, Erik; Bader, Simon; et al. (Geburtshilfe und Frauenheilkunde, 2022)
For patients with advanced breast cancer, several novel therapies have emerged in recent years, including CDK4/6 inhibitors, immune checkpoint inhibitors, PARP inhibitors, alpelisib, tucatinib and trastuzumab-deruxtecan, and sacituzumab-govitecan, which have transformed and expanded the therapeutic landscape for patients with advanced breast cancer. Some of these substances have now been approved for use in the early stages of the disease, or are expected to be approved in the near future, so the therapeutic landscape will change once again. Therefore, current scientific efforts are focused on the introduction of new substances and understanding their mechanisms of progression and efficacy. This review summarizes recent developments with reference to recent publications and conferences. Findings on the treatment of patients with HER2-positive breast cancer and brain metastases are presented, as are a number of studies looking at biomarkers in patients with HER2-negative, hormone receptor-positive breast cancer. In particular, the introduction of oral selective estrogen receptor degraders provides new opportunities to establish biomarker-based therapy. Molecular diagnostics is establishing itself as a diagnostic marker and parameter of progression.
CRIS-Team Scopus Importer:2022-08-05
Keywords: ADC; biomarker; breast cancer; metastatic; PD-L1

Update Breast Cancer 2022 Part 3 - Early-Stage Breast Cancer. - Fehm, Tanja N.; Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Belleville, Erik; Untch, Michael; Thill, Marc; et al. (Geburtshilfe und Frauenheilkunde, 2022)
This review summarizes recent developments in the prevention and treatment of patients with early-stage breast cancer. The individual disease risk for different molecular subtypes was investigated in a large epidemiological study. With regard to treatment, new data are available from long-term follow-up of the Aphinity study, as well as new data on neoadjuvant therapy with atezolizumab in HER2-positive patients. Biomarkers, such as residual cancer burden, were investigated in the context of pembrolizumab therapy. A Genomic Grade Index study in elderly patients is one of a group of studies investigating the use of modern multigene tests to identify patients with an excellent prognosis in whom chemotherapy may be avoided. These and other aspects of the latest developments in the diagnosis and treatment of breast cancer are described in this review.
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Update Breast Cancer 2022 Part 4 - Advanced-Stage Breast Cancer. - Aktas, Bahriye; Fehm, Tanja N.; Welslau, Manfred; Mueller, Volkmar; Lueftner, Diana; Schuetz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Belleville, Erik; Untch, Michael; et al. (Geburtshilfe und Frauenheilkunde, 2022)
For the treatment of patients with advanced HER2-negative hormone receptor-positive breast cancer, several substances have been introduced into practice in recent years. In addition, other drugs are under development. A number of studies have been published over the past year which have shown either an advantage for progression-free survival or for overall survival. This review summarizes the latest results, which have been published at current congresses or in specialist journals, and classifies them in the clinical treatment context. In particular, the importance of therapy with CDK4/6 inhibitors - trastuzumab deruxtecan, sacituzumab govitecan and capivasertib - is discussed. For trastuzumab deruxtecan, an overall survival benefit in HER2-negative breast cancer with low HER2 expression (HER2-low expression) was reported in the Destiny-Breast-04 study. Similarly, there was an overall survival benefit in the FAKTION study with capivasertib. The lack of overall survival benefit for palbociclib in the first line of therapy raises the question of clinical classification.
EVALuna2:511788

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer - Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Lüftner, Diana; Schütz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Beierlein, Milena; Belleville, Erik; Untch, Michael; et al. (Geburtshilfe und Frauenheilkunde, 2023)
The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.
CRIS-Team Scopus Importer:2023-03-31
Keywords: breast cancer; chemotherapy; surgery; therapy standard

Update Breast Cancer 2022 Part 6 – Advanced-Stage Breast Cancer - Lüftner, Diana; Lux, Michael P.; Fehm, Tanja N.; Welslau, Manfred; Müller, Volkmar; Schütz, Florian; Fasching, Peter; Janni, Wolfgang; Thomssen, Christoph; Witzel, Isabell; Beierlein, Milena; Belleville, Erik; et al. (Geburtshilfe und Frauenheilkunde, 2023)
Large-scale study programs on CDK4/6 inhibitors, targeted therapies, and antibody-drug conjugates launched in recent years have yielded results from current studies which are now being published in journals and presented at international conferences. In this context, new results are available from the major CDK4/6 inhibitor studies. Also, an increasing amount of data is being published from large-scale genomic studies on efficacy and resistance mechanisms in patients treated with CDK4/6 inhibitors. These results now form the basis for further research plans to investigate combination therapies and treatment sequencing. Based on the latest published results, sacituzumab govitecan is now available as a second antibody-drug conjugate; this brings an advantage in terms of overall survival for patients with hormone receptor-positive (HRpos)/HER2-negative (HER2neg) breast cancer. In this review article, we summarize the latest developments and place them in context according to the current status of research.
CRIS-Team Scopus Importer:2023-03-31
Keywords: advanced breast cancer; chemotherapy; therapy standard

Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus fulvestrant - Neven, P.; Fasching, Peter; Chia, S.; Jerusalem, G.; De Laurentiis, M.; Im, S. A.; Petrakova, K.; Bianchi, G. V.; Martín, M.; Nusch, A.; Sonke, G. S.; De la Cruz-Merino, L.; et al. (Breast Cancer Research, 2023)
Background: The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. Methods: Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results: At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. Conclusions: This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2− ABC.
CRIS-Team Scopus Importer:2023-09-08
Keywords: Advanced breast cancer; CDK4/6 inhibitor; First line; Overall survival; Ribociclib

Updated overall survival (OS) results from the first-line (1L) population in the phase III MONALEESA-3 trial of postmenopausal patients (PTS) with HR+/HER2-advanced breast cancer (ABC) treated with ribociclib (RIB) plus fulvestrant (FUL) - Neven, P.; Fasching, Peter; Chia, S.; Jerusalem, G.; De Laurentiis, M.; Im, S. -A.; Petrakova, K.; Bianchi, G. V.; Martin Jimenez, M.; Nusch, A.; Sonke, G. S.; De La Cruz Merino, L.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Update in the certification of endometriosis centers Neues in der Zertifizierung von Endometriosezentren - Schaefer, Sebastian D.; Sillem, Martin; Schweppe, Karl-Werner; Burghaus, Stefanie; Beckmann, Matthias (Gynäkologe, 2021)
Endometriosis is among the most frequent diseases of women during reproductive age. The disease itself but also its treatment significantly impairs quality of life. Top-level specialized centers have been established to ensure diagnosis and treatment. The certification process defined by Stiftung Endometriose-Forschung (SEF), European Endometriosis League (EEL) and patient self-help organisations is intended to guarantee comparable quality. Diagnosis and treatment need to be based on current guidelines. The redefinition of the term center by the German Gemeinsame Bundesausschuss (G-BA) has made it necessary to adapt the established staging concept. In the future specialized “endometriosis practices”, “endometriosis units” and “endometriosis centers” will be certified according to predefined criteria.
CRIS-Team Scopus Importer:2021-05-21
Keywords: Guidelines; Integrative medicine; Quality of life; Reproduction; Shared decision making

Update Mammakarzinom 2019 Teil 1 – Implementierung der Ergebnisse neuer Studienkonzepte beim frühen Mammakarzinom in die klinische Praxis - Hartkopf, Andreas D.; Müller, Volkmar; Wöckel, Achim; Lux, Michael P.; Janni, Wolfgang; Nabieva, Naiba; Taran, Florin Andrei; Ettl, Johannes; Lüftner, Diana; Belleville, Erik; Schütz, Florian; Fasching, Peter; et al. (TumorDiagnostik & Therapie, 2019)
For many years, small but significant advancements have been made time and again in the prevention and treatment of early breast cancer. The so-called panel gene analyses are becoming more and more important in prevention, since the risk due to the tested genes is better understood and as a result, concepts for integration in health care can be developed. In the adjuvant situation, the first study in the so-called postneoadjuvant situation was able to demonstrate a clear improvement in the prognosis with an absent pathological complete remission following trastuzumab or pertuzumab + trastuzumab. Additional studies with this post-neoadjuvant therapeutic concept are still being conducted at present. The CDK4/6 inhibitors which had shown a significant improvement in progression-free survival in a metastatic situation are currently being tested in the adjuvant situation in large therapeutic studies. These and other new data for the treatment or prevention of primary breast cancer are presented in this review against the backdrop of current studies.
CRIS-Team Scopus Importer:2019-09-17
Keywords: adjuvant therapy; early breast cancer; Katherine; neoadjuvant therapy; prevention; TDM1

Update S3-Leitlinie Zervixkarzinom: Diagnostik, Therapie und Nachsorge - Stübs, Frederik; Beckmann, Matthias; Fehm, Tanja (Best Practice Onkologie, 2022)
There is constant progress in the treatment of women with cervical cancer. Therefore, the German S3 guideline requires regular revision. The new statements and recommendations are based on a systematic literature review. The revision process involved around 50 specialist societies under the expert guidance of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). The new standard of care in surgical therapy for cervical cancer up to FIGO stage IB1 is open radical hysterectomy. The evidence base for the role of intensity-modulated radiotherapy and individualized brachytherapy was strengthened. Patients with metastatic cervical cancer benefit from addition of bevacizumab to standard chemotherapy in first-line treatment. From the second line onward, the use of pembrolizumab is recommended for women with PD-L1-positive cervical cancer.
CRIS-Team Scopus Importer:2022-07-08
Keywords: Bevacizumab; Brachytherapy; Open radical hysterectomy; Pembrolizumab; PET-CT

Updates on the role of receptor activator of nuclear factor κB/receptor activator of nuclear factor κB ligand/osteoprotegerin pathway in breast cancer risk and treatment - Bayer, Christian M.; Beckmann, Matthias; Fasching, Peter (Current Opinion in Obstetrics & Gynecology, 2017)
PURPOSE OF REVIEW: Treatment with bisphosphonates and denosumab is the standard of care in bone metastatic disease. In addition, the adjuvant therapy of denosumab or bisphosphonates is very effective to prevent loss of bone mineral density, for example in osteoporosis. However, it is still unclear if this therapy has an influence on preventing cancer. RECENT FINDINGS: Since the identification of novel genes in the 1980s, it took about 30 years until denosumab, as a fully human mAb against receptor activator of nuclear factor (NF)-κB ligand (RANKL), could be introduced to clinical practice. The discovery of the receptor activator of NF-κB/RANKL/osteoprotegerin pathway in the 1990s is an example of how modern databases of genes were utilized to discover new pathways relevant to a variety of diseases. The essential role of this pathway for the function, differentiation and survival of osteoclasts, and the influence on the bone microenvironment helped to understand the vicious circle of bone resorption and destruction in many skeletal diseases. SUMMARY: In the following review, we discuss the important role of rational targeting concerning receptor activator of NF-κB/RANKL/osteoprotegerin and the bisphosphonate therapy and provide an update for the related treatment of patients suffering from breast cancer and further implications for clinical practice and research using denosumab as a potential chemoprevention in BRCA1-related breast cancer.
EVALuna2:36158

Usability and feasibility of PreventS-MD web app for stroke prevention - Feigin, Valery L.; Krishnamurthi, Rita; Medvedev, Oleg; Merkin, Alexander; Nair, Balakrishnan; Kravchenko, Michael; Jalili-Moghaddam, Shabnam; Barker-Collo, Suzanne; Ratnasabapathy, Yogini; Skinner, Luke; Owolabi, Mayowa; Norrving, Bo; et al. (International Journal of Stroke, 2023)
Background: Most strokes and cardiovascular diseases (CVDs) are potentially preventable if their risk factors are identified and well controlled. Digital platforms, such as the PreventS-MD web app (PreventS-MD) may aid health care professionals (HCPs) in assessing and managing risk factors and promoting lifestyle changes for their patients. Methods: This is a mixed-methods cross-sectional two-phase survey using a largely positivist (quantitative and qualitative) framework. During Phase 1, a prototype of PreventS-MD was tested internationally by 59 of 69 consenting HCPs of different backgrounds, age, sex, working experience, and specialties using hypothetical data. Collected comments/suggestions from the study HCPs in Phase 1 were reviewed and implemented. In Phase 2, a near-final version of PreventS-MD was developed and tested by 58 of 72 consenting HCPs using both hypothetical and real patient (n = 10) data. Qualitative semi-structured interviews with real patients (n = 10) were conducted, and 1 month adherence to the preventive recommendations was assessed by self-reporting. The four System Usability Scale (SUS) groups of scores (0–50 unacceptable; 51–68 poor; 68–80.3 good; >80.3 excellent) were used to determine usability of PreventS-MD. Findings: Ninety-nine HCPs from 27 countries (45% from low- to middle-income countries) participated in the study, and out of them, 10 HCPs were involved in the development of PreventS before the study, and therefore were not involved in the survey. Of the remaining 89 HCPs, 69 consented to the first phase of the survey, and 59 of them completed the first phase of the survey (response rate 86%), and 58 completed the second phase of the survey (response rate 84%). The SUS scores supported good usability of the prototype (mean score = 80.2; 95% CI [77.0–84.0]) and excellent usability of the final version of PreventS-MD (mean score = 81.7; 95% CI [79.1–84.3]) in the field. Scores were not affected by the age, sex, working experience, or specialty of the HCPs. One-month follow-up of the patients confirmed the high level of satisfaction/acceptability of PreventS-MD and (100%) adherence to the recommendations. Interpretation: The PreventS-MD web app has a high level of usability, feasibility, and satisfaction by HCPs and individuals at risk of stroke/CVD. Individuals at risk of stroke/CVD demonstrated a high level of confidence and motivation in following and adhering to preventive recommendations generated by PreventS-MD.
CRIS-Team Scopus Importer:2023-09-15
Keywords: epidemiology; hypertension; prevention; risk factors; Stroke; stroke facilities

Usability and Suitability of the Omics-Integrating Analysis Platform tranSMART for Translational Research and Education - Christoph, Jan; Knell, Christian; Boßerhoff, Anja Katrin; Naschberger, Elisabeth; Stürzl, Michael; Rübner, Matthias; Seuß, Hannes; Ruh, Manuel; Prokosch, Hans-Ulrich; Sedlmayr, Brita (Applied Clinical Informatics, 2017)
Platforms like tranSMART assist researchers in analyzing clinical and corresponding omics data. Usability is an important, yet often overlooked, factor affecting the adoption and meaningful use. Analyses on the specific needs of translational researchers and considerations about the application of such platforms for education are rare. The aim of this study was to test whether tranSMART can be used in education and how well medical students and professional researchers can handle it; to identify which kind of translational researchers-in terms of skills, experienced limitations, and available data-can take advantage of tranSMART; and to evaluate the usability and to generate recommendations for improvements. An online-based test has been done by medical students (N = 109) and researchers (N = 26). The test comprised 13 tasks in the context of four typical research scenarios based on experimental and clinical data. A web questionnaire was provided to identify both the needs and the conditions of research as well as to evaluate the system's usability based on the "System Usability Scale" (SUS). Students and researchers were able to handle tranSMART well and coped with most scenarios: cohort identification, data exploration, hypothesis generation, and hypothesis validation were answered with a rate of correctness between 82 and 100%. Of the total, 72.2% of the teaching researchers considered tranSMART suitable for their lessons and 84.6% of the researchers considered the platform useful for their daily work; 65.4% of the researchers named the nonavailability of a platform like tranSMART as a restriction on their research. The usability was rated "acceptable" with a SUS of 70.8. tranSMART is potentially suitable for education purposes and fits most of the needs of translational researchers. Improvements are needed on the presentation of analysis results and on the guidance of users through the analysis, especially to ensure the compliance of the analysis with the requirements of statistical testing.
EVALuna2:195

Use of a molecular Registry (PRAEGNANT) for Patient-Selection and Biomarker-Analysis for the SHERBOC Study - Hübner, Hanna; Kurbacher, C.; Kuesters, G.; Hartkopf, A. D.; Lux, M. P.; Huober, J.; Volz, B.; Taran, F. A.; Overkamp, F.; Tesch, H.; Häberle, Lothar; Lueftner, D.; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Use of complementary and integrative medicine among German breast cancer patients: predictors and implications for patient care within the PRAEGNANT study network - Fremd, Carlo; Hack, Carolin; Schneeweiss, Andreas; Rauch, Geraldine; Wallwiener, Diethelm; Brucker, Sara Yvonne; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Tesch, Hans; Fehm, Tanja; Hadji, Peyman; et al. (Archives of Gynecology and Obstetrics, 2017)
PURPOSE: The present study aims to analyze a cohort of advanced breast cancer patients in Germany to assess their interest in complementary and alternative medicine (CAM) and patient's use of most frequent CAM methods. PATIENTS AND METHODS: Based on the PREGNANT real-time breast cancer registry which is a multicenter study in Germany, questionnaires of 580 patients with advanced breast cancer were evaluated. The implemented questionnaire for CAM asked for general interest in CAM and for patient's use of different CAM methods at present and in the past. The interest and application of CAM were analyzed for association with patients' characteristics such as tumor, patient, and therapy characteristics. RESULTS: In total, 436 out of 580 (75%) patients claimed to be interested in CAM. Further, interest in CAM is significantly correlated with younger age and absence of metastasis at the time of diagnosis. Multivariate analysis confirmed the patient's age and distant disease status at the time of diagnosis as related to interest in CAM. A total of 56.4% of patients applied any CAM method in the past. Moreover, with increasing lines of therapies, the more frequent use of CAM was observed. Hereby, praying, vitamin supplements, and other food supplements were most frequently applied. CONCLUSION: Our data demonstrate high overall interest and frequent use of CAM in advanced breast cancer patients supporting a strong demand of breast cancer patients for complementary counseling and treatments additional to the established cancer therapies. It is indispensable to implement counseling and evidence-based complementary treatments into clinical routine of cancer centers and to adapt postgraduate medical education, respectively.
EVALuna2:36145

Use of Granulocyte-colony Stimulating Factor During Chemotherapy and Its Association With CA27.29 and Circulating Tumor Cells-Results From the SUCCESS A Trial - Hepp, Philip; Fasching, Peter; Beckmann, Matthias; Fehm, Tanja; Salmen, Jessica; Hagenbeck, Carsten; Jaeger, Bernadette; Widschwendter, Peter; De Gregorio, Nikolaus; Schochter, Fabienne; Mahner, Sven; Harbeck, Nadia; et al. (Clinical Breast Cancer, 2018)
Little is known about the effect of granulocyte colony-stimulating factor (G-CSF) treatment during adjuvant chemotherapy on prognostic markers. The present study explored the association between G-CSF and changes in cancer antigen (CA)27.29 and circulating tumor cell (CTC) levels during therapy.A total of 3754 node-positive or high-risk node-negative early-stage breast cancer patients were treated within the SUCCESS-A trial (simultaneous study of gemcitabine-docetaxel combination adjuvant treatment, as well as extended bisphosphonate and surveillance-trial). CA27.29 and CTCs were determined before the start and within 6 weeks after the end of chemotherapy.Overall, 1324 of the 2646 patients (50.0%) available for analysis had >= 1 G-CSF applications during chemotherapy. G-CSF application was significantly associated with CA27.29 status before and after chemotherapy (? = 30.6, df = 3; P < .001), because 238 patients (18.0%) with G-CSF treatment but only 146 (11.0%) without G-CSF treatment switched from a negative CA27.29 status before to a positive CA27.29 status after chemotherapy. In addition, patients with G-CSF application showed a significantly greater increase in CA27.29 levels after chemotherapy compared with patients without any G-CSF application during chemotherapy (Mann-Whitney U test; Z = -7.81, P < .001). No significant association was found between G-CSF application and CTC status before or after chemotherapy (? = 1.2, df = 3; P = .75).Cautious interpretation is needed regarding elevated levels of MUC-1-derived tumor markers such as CA27.29 shortly after adjuvant chemotherapy when G-CSF has been given, because G-CSF treatment was associated with increased CA27.29 levels after chemotherapy.
EVALuna2:56150

Using automated texture features to determine the probability for masking of a tumor on mammography, but not ultrasound - Haeberle, Lothar; Hack, Carolin; Heusinger, Katharina; Wagner, Florian; Jud, Sebastian; Uder, Michael; Beckmann, Matthias; Schulz-Wendtland, Rüdiger; Wittenberg, Thomas; Fasching, Peter (European Journal of Medical Research, 2017)
BACKGROUND: Tumors in radiologically dense breast were overlooked on mammograms more often than tumors in low-density breasts. A fast reproducible and automated method of assessing percentage mammographic density (PMD) would be desirable to support decisions whether ultrasonography should be provided for women in addition to mammography in diagnostic mammography units. PMD assessment has still not been included in clinical routine work, as there are issues of interobserver variability and the procedure is quite time consuming. This study investigated whether fully automatically generated texture features of mammograms can replace time-consuming semi-automatic PMD assessment to predict a patient's risk of having an invasive breast tumor that is visible on ultrasound but masked on mammography (mammography failure). METHODS: This observational study included 1334 women with invasive breast cancer treated at a hospital-based diagnostic mammography unit. Ultrasound was available for the entire cohort as part of routine diagnosis. Computer-based threshold PMD assessments ("observed PMD") were carried out and 363 texture features were obtained from each mammogram. Several variable selection and regression techniques (univariate selection, lasso, boosting, random forest) were applied to predict PMD from the texture features. The predicted PMD values were each used as new predictor for masking in logistic regression models together with clinical predictors. These four logistic regression models with predicted PMD were compared among themselves and with a logistic regression model with observed PMD. The most accurate masking prediction was determined by cross-validation. RESULTS: About 120 of the 363 texture features were selected for predicting PMD. Density predictions with boosting were the best substitute for observed PMD to predict masking. Overall, the corresponding logistic regression model performed better (cross-validated AUC, 0.747) than one without mammographic density (0.734), but less well than the one with the observed PMD (0.753). However, in patients with an assigned mammography failure risk >10%, covering about half of all masked tumors, the boosting-based model performed at least as accurately as the original PMD model. CONCLUSION: Automatically generated texture features can replace semi-automatically determined PMD in a prediction model for mammography failure, such that more than 50% of masked tumors could be discovered.
UnivIS-Import:2017-12-18:Pub.2017.tech.IMMD.IMMD9.usinga
Keywords: Mammographic density; Mammography screening; Masking; Risk prediction; Sensitivity; Texture analysis; Variable selection

Using Probability for Pathological Complete Response (pCR) as a Decision Support Marker for Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer Patients - a Survey Among Physicians - Gaß, Paul; Untch, Michael; Mueller, Volkmar; Moebus, Volker; Thomssen, Christoph; Häberle, Lothar; Erber, Ramona; Hein, Alexander; Jud, Sebastian; Lux, Michael P.; Hack, Carolin; Hartmann, Arndt; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Background: In women with early breast cancer, a pathological complete response (pCR) after neoadjuvant chemotherapy is reported to be associated with an improvement of the survival. The aim of this survey among physicians was to investigate whether the probability of achieving pCR in patients with a hormone receptor-positive, HER2-negative disease encourages physicians to recommend neoadjuvant chemotherapy. Methods: The study was conducted via an online survey that was sent to 493 physicians, who were either known as members of national guideline committees, heads of breast cancer centers, being high recruiters in clinical trials or leading a private practice. Participants were asked about a specific case that should resemble patients for whom it is unclear, whether they should be treated with chemotherapy. Results: 113 (24.5%) physicians participated at the survey, out of which 96.5% had a work experience of more than 10 years and 94.7% were board certified in their specialty. A total of 84.1% would consider pCR for a decision concerning neoadjuvant chemotherapy. With regard to the pCR probability, 2.7 and 10.6% of the participants demanded at least a pCR rate of 5 and 10%, respectively, while 25.7% were satisfied with 20% probability, and another 25.7% with a pCR rate of 30%. Conclusions: The vast majority of the long-term experienced physicians would embrace the implementation of a further method such as the prediction of pCR probability in clinical routine to support decision making regarding the necessity of neoadjuvant chemotherapy. The cut-off of around 30% pCR probability seems to be a realizable rate to distinguish patient groups.
EVALuna2:34856

Uterine contractility changes in a perfused swine uterus model induced by local anesthetics procaine, lidocaine, and ropivacaine - Weinschenk, Fabian; Dittrich, Ralf; Mueller, Andreas; Lotz, Laura; Beckmann, Matthias; Weinschenk, Stefan W. (PLoS ONE, 2018)
BACKGROUND: Local anesthetics (LAs) are increasingly used as therapeutics due to their multiple molecular effects. They may be potential agents also in gynecology and reproductive medicine. The objective of this study was to investigate the contractility response of the perfused swine uterus to different concentrations of the LAs procaine, lidocaine, and ropivacaine. METHODS AND FINDINGS: In an extracorporeal perfusion model with fresh swine uteri, effects of administered boli of these three LAs in concentrations of 0.1 mg/mL, 0.5 mg/mL and 1.0 mg/mL on uterine contractility and peristalsis were assessed using an intrauterine double-chip micro-catheter. A dose-dependent increase in intrauterine pressure (IUP) in the isthmus and corpus uteri was observed after the administration of the ester-LA procaine 0.1, 0.5, and 1.0%, which was not seen with lower concentrations, or buffer solution. An increase-decrease curve was found after increasing concentrations of the amide-LA lidocaine and ropivacaine, with an IUP plateau with 0.1 and 0.5%, and a decrease with 1% (p<0.01). All reactions were seen in both the isthmus and corpus uteri. The difference of the contractility pattern between ester- and amide-LA at 1% concentration was significant. CONCLUSION: LAs dose-dependently modulate contractility in non-pregnant swine uteri. The amid-LAs lidocaine and ropivacaine reduce contractility in higher concentrations and may be used as therapeutics in disorders with increased uterine contractility, as dysmenorrhoea, endometriosis, and infertility. The multiple molecular effects of LAs may explain these effects. This in-vitro pilot study in vitro provides initial data for designing further studies to transfer the results onto humans.
EVALuna2:209956

Utility of the CPS + EG scoring system in triple-negative breast cancer treated with neoadjuvant chemotherapy - Marmé, Frederik; Solbach, Christine; Michel, Laura; Schneeweiss, Andreas; Blohmer, Jens Uwe; Huober, Jens; Fasching, Peter; Jackisch, Christian; Nekljudova, Valentina; Link, Theresa; Rhiem, Kerstin; Rey, Julia; et al. (European Journal of Cancer, 2021)
Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is associated with superior survival. This association is strongest in triple-negative breast cancer (TNBC). The CPS + EG system, based on pre-treatment clinical (CS) and post-treatment pathological stage (PS), oestrogen-receptor status (E) and grade (G), leads to a refined estimate of prognosis after NACT in all-comers and hormone receptor–positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Here, we investigate if CPS + EG scoring provides a superior estimate of prognosis in TNBC to select patients for postneoadjuvant therapy. Methods: We calculated the CPS + EG score for 1795 patients with TNBC from 8 prospective German trials. Five-year disease-free survival (DFS) and overall survival estimates were calculated using the Kaplan-Meier method. Results: In TNBC, patients with pCR (ypT0/is ypN0, n = 822, 45.8%) had a 5-year DFS of 86%, whereas patients with residual American Joint Committee on Cancer stage I disease (n = 383; 21.3%) had a 5-year DFS of 77.5%.CPS + EG led to superior prognostic information compared with that provided by the clinical stage, but it was inferior to the prognostic information provided by the pathological stage (c-index statistics, p < 0.001). CPS + EG did not discriminate prognosis within the two best prognostic groups (score 1 and 2; n = 362; 37.2%). In contrast, pCR status added prognostic information beyond CPS + EG. Patients with a CPS + EG score of 3 had a 5-year DFS rate of 64% overall, but those with pCR had a 5-year DFS rate of 84%, and those without pCR had a 5-year DFS rate of only 49.7%. Conclusions: In TNBC, CPS + EG scoring provided inferior prognostic information compared with the pathological stage and was unable to identify patients without pCR and with a sufficiently good prognosis, who could avoid postneoadjuvant therapy. pCR remains the strongest and most clinically useful prognostic factor after NACT. Other biologic factors beyond pCR are needed in TNBC.
CRIS-Team Scopus Importer:2021-07-23
Keywords: CPS + EG; Neoadjuvant therapy; Prognosis; Triple-negative breast cancer

Utility of the CPS plus EG scoring system in triple-negative breast cancer treated with neoadjuvant chemotherapy - Marme, F.; Solbach, C.; Michel, L.; Fasching, Peter; Schneeweiss, A.; Blohmer, J. -U.; Rezai, M.; Huober, J.; Jackisch, C.; Nekljudova, V.; Link, T.; Rhiem, K.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Vaginal Birth at Term – Part 1. Guideline of the DGGG, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/083, December 2020) - Abou-Dakn, Michael; Schäfers, Rainhild; Peterwerth, Nina; Asmushen, Kirsten; Bässler-Weber, Susanne; Boes, Ulrike; Bosch, Andrea; Ehm, David; Fischer, Thorsten; Greening, Monika; Hartmann, Katharina; Heller, Günther; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Purpose This guideline aims to summarize the current state of knowledge about vaginal birth at term. The guideline focuses on definitions of the physiological stages of labor as well as differentiating between various pathological developments and conditions. It also assesses the need for intervention and the options to avoid interventions. This first part presents recommendations and statements about patient information and counselling, general patient care, monitoring of patients, pain management and quality control measures for vaginal birth. Methods The German recommendations largely reproduce the recommendations of the National Institute for Health and Care Excellence (NICE) CG 190 guideline Intrapartum care for healthy women and babies. Other international guidelines were also consulted in specific cases when compiling this guideline. In addition, a systematic search and analysis of the literature was carried out using PICO questions, if this was considered necessary, and other systematic reviews and individual studies were taken into account. For easier comprehension, the assessment tools of the Scottish Intercollegiate Guidelines Network (SIGN) were used to evaluate the quality of the additionally consulted studies. Otherwise, the GRADE system was used for the NICE guideline and the evidence reports of the IQWiG were used to evaluate the quality of the evidence. Recommendations Recommendations and statements were formulated based on identified evidence and/or a structured consensus.
CRIS-Team Scopus Importer:2022-11-25
Keywords: delivery; guideline; term; vaginal birth

Vaginal Birth at Term - Part 2Guideline of the DGGG, OEGGG and SGGG (S3-Level, AWMF Registry No. 015/083, December 2020) - Abou-Dakn, Michael; Schäfers, Rainhild; Peterwerth, Nina; Asmushen, Kirsten; Bässler-Weber, Susanne; Boes, Ulrike; Bosch, Andrea; Ehm, David; Fischer, Thorsten; Greening, Monika; Hartmann, Katharina; Heller, Günther; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Purpose This guideline aims to summarize the current state of knowledge about vaginal birth at term. The guideline focuses on definitions of the physiological stages of labor as well as differentiating between various pathological developments and conditions. It also assesses the need for intervention and the options to avoid interventions. The second part of this guideline presents recommendations and statements on care during the dilation and expulsion stages as well as during the placental/postnatal stage. Methods The German recommendations largely reproduce the recommendations of the National Institute for Health and Care Excellence (NICE) CG190 guideline Intrapartum care for healthy women and babies. Other international guidelines were also consulted in individual cases when compiling this guideline. In addition, a systematic search and analysis of the literature was carried out using PICO questions where necessary, and other systematic reviews and individual studies were taken into account. For easier comprehension, the assessment tools of the Scottish Intercollegiate Guidelines Network (SIGN) were used to evaluate the quality of additionally consulted studies. Otherwise, the GRADE system was used for the NICE guideline, and the evidence reports of the IQWiG were used to evaluate the quality of the evidence. Recommendations Recommendations and statements were formulated based on identified evidence and/or a structured consensus.
CRIS-Team Scopus Importer:2022-11-25
Keywords: delivery; guideline; term; vaginal birth

Validation of the MammaTyper (R) pathological complete response (pCR)-score as a predictor for response after neoadjuvant chemotherapy (NACT) in patients with early breast cancer (BC) - Fasching, Peter; Laible, M.; Weber, K. E.; Wirtz, R. M.; Denkert, C.; Schlombs, K.; Schmatloch, S.; Camara, O.; Lueck, H. J.; Huober, J.; Karn, T.; Van Mackelenbergh, M. T.; et al. (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Variable expression of the disialoganglioside gd2 in breast cancer molecular subtypes - Erber, Ramona; Kailayangiri, Sareetha; Hübner, Hanna; Rübner, Matthias; Hartmann, Arndt; Häberle, Lothar; Meyer, Julia; Völkl, Simon; Mackensen, Andreas; Landgraf, Laura; Geppert, Carol-Immanuel; Schulz-Wendtland, Rüdiger; et al. (Cancers, 2021)
The disialoganglioside GD2 is a tumor-associated antigen that may allow for the application of targeted immunotherapies (anti-GD2 antibodies, GD2 CAR T cells) in patients with neuroblastoma and other solid tumors. We retrospectively investigated GD2 expression in a breast cancer cohort, using immunohistochemistry (IHC) and immunofluorescence (IF) on tissue microarrays (TMAs), and its impact on survival. GD2 expression on IHC (n = 568) and IF (n = 503) was investigated in relation to subtypes and patient outcome. Overall, 50.2% of the 568 IHC-assessed samples and 69.8% of the 503 IF-assessed samples were GD2-positive. The highest proportion of GD2-positive tumors was observed in luminal tumors. Significantly fewer GD2-positive cases were detected in triple-negative breast cancer (TNBC) compared with other subtypes. The proportion of GD2-expressing tumors were significantly lower in HER2-positive breast cancer in comparison with luminal tumors on IF staining (but not IHC). GD2 expression of IHC or IF was not significantly associated with disease-free or overall survival, in either the overall cohort or in individual subtypes. However, GD2 expression can be seen in more than 50% of breast cancer cases, with the highest frequency in hormone receptorpositive tumors. With this high expression frequency, patients with GD2-positive advanced breast cancer of all subtypes may benefit from GD2-targeting immunotherapies, which are currently subject to clinical testing.
CRIS-Team Scopus Importer:2021-11-12
Keywords: Breast cancer; Disialoganglioside; GD2; Immunofluorescence; Immunohistochemistry; Prognosis

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility - Earp, Madalene; Tyrer, Jonathan P.; Winham, Stacey J.; Lin, Hui-Yi; Chornokur, Ganna; Dennis, Joe; Aben, Katja K. H.; Anton-Culver, Hoda; Antonenkova, Natalia; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias; et al. (PLoS ONE, 2018)
Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
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Variation in NF-?B signaling pathways and survival in invasive epithelial ovarian cancer - Block, Matthew S.; Charbonneau, Bridget; Vierkant, Robert A.; Fogarty, Zachary; Bamlet, William R.; Pharoah, Paul D. P.; Chenevix-Trench, Georgia; Rossing, Mary Anne; Cramer, Daniel; Pearce, Celeste Leigh; Schildkraut, Joellen; Menon, Usha; et al. (Cancer Epidemiology Biomarkers & Prevention, 2014)
Survival in epithelial ovarian cancer (EOC) is influenced by the host immune response, yet the key genetic determinants of inflammation and immunity that affect prognosis are not known. The nuclear factor-?B (NF-?B) transcription factor family plays an important role in many immune and inflammatory responses, including the response to cancer. We studied common inherited variation in 210 genes in the NF-?B family in 10,084 patients with invasive EOC (5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous) from the Ovarian Cancer Association Consortium. Associations between genotype and overall survival were assessed using Cox regression for all patients and by major histology, adjusting for known prognostic factors and correcting for multiple testing (threshold for statistical significance, P < 2.5 × 10(-5)). Results were statistically significant when assessed for patients of a single histology. Key associations were with caspase recruitment domain family, member 11 (CARD11) rs41324349 in patients with mucinous EOC [HR, 1.82; 95% confidence interval (CI), 1.41-2.35; P = 4.13 × 10(-6)] and tumor necrosis factor receptor superfamily, member 13B (TNFRSF13B) rs7501462 in patients with endometrioid EOC (HR, 0.68; 95% CI, 0.56-0.82; P = 2.33 × 10(-5)). Other associations of note included TNF receptor-associated factor 2 (TRAF2) rs17250239 in patients with high-grade serous EOC (HR, 0.84; 95% CI, 0.77-0.92; P = 6.49 × 10(-5)) and phospholipase C, gamma 1 (PLCG1) rs11696662 in patients with clear cell EOC (HR, 0.43; 95% CI, 0.26-0.73; P = 4.56 × 10(-4)). These associations highlight the potential importance of genes associated with host inflammation and immunity in modulating clinical outcomes in distinct EOC histologies.
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Venöse Luftembolie bei vaginalen Verletzungen durch Geschlechtsverkehr - Zack, F.; Zinka, B.; Beckmann, Matthias; Banaschak, Sibylle; Fischer, H.; Gabriel, P.; Gerber, B.; Costa, S. D.; Ledwon, P.; Schwenzer, T.; Buettner, A. (Rechtsmedizin, 2019)
Background: In a criminal trial in Germany in 2013, a medical expert nominated by the defence stated in the appeal trial the controversially discussed opinion that a woman had died from an air embolism due to vaginal intercourse with exclusively penile penetration and injury to the vaginal wall. This diagnosis had been established by the expert based on histological examination of the lungs and vaginal injuries years after the woman‘s death. Objective: The frequency of the diagnosis “air embolism as a result of vaginal injuries due to intravaginal intercourse” and the modality of the diagnosis were reviewed. Material and methods: A selective literature review was performed. Furthermore, questionnaires were sent to all forensic medical institutes and to directors and chief physicians of gynecological clinics of large cities in Germany. Results: In the literature two case reports could be found, which by critical analysis showed significant errors in the diagnosis according to the state of science at the time of publication. In over 300,000 autopsies performed between 1990 and 2016, the 26 forensic medical institutes in Germany, which had answered the questionnaire, had never diagnosed “air embolism as a result of vaginal injuries due to intravaginal intercourse”. All 32 professionally experienced gynecologists who responded to the questionnaire had never in their career treated survived or fatal cases of air embolism after vaginal injuries through sexual intercourse or had knowledge of them. Conclusion: According to the survey and critical analysis of the very few published case reports, there is no evidence for a diagnosis of the cause of death as air embolism after vaginal injuries. When diagnosing a fatal venous air embolism, scientific standards should be strictly followed. A diagnosis made solely by histological examination was and is not possible according to the state of the art in forensic medicine and thus violates the principles of expert medical opinions.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Cause of death; Expert opinion; Pregnancy; Questionnaire; Sexual behavior

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment - Brunner, Michaela; Roth, H.; Günther, K.; Grützmann, Robert; Matzel, Klaus E. (International Journal of Colorectal Disease, 2019)
PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.
CRIS-Team Scopus Importer:2019-10-01
Keywords: Biological mesh; Functional outcome; Laparoscopic ventral rectopexy; Recurrent posterior compartment prolapse; Recurrent rectal prolapse

Ventral rectopexy with biological mesh: short-term functional results - Brunner, Michaela; Roth, H.; Guenther, K.; Grützmann, Robert; Matzel, K. E. (International Journal of Colorectal Disease, 2018)
PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.
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Veranstaltungsbericht: 10. Wissenschaftliches Symposium der AGO-TraFo - Banys-Paluchowski, Malgorzata; Antoniadis, Sophia; Hein, Alexander; Fehm, Tanja N.; Arnold, Norbert; Fasching, Peter (Geburtshilfe und Frauenheilkunde, 2018)
CRIS-Team Scopus Importer:2021-07-19

Veranstaltungsbericht – 11. Wissenschaftliches Symposium der AGO-TraFo - Banys-Paluchowski, Malgorzata; Wunderle, Marius; Fehm, Tanja N.; Arnold, Norbert; Fasching, Peter (Geburtshilfe und Frauenheilkunde, 2019)
CRIS-Team Scopus Importer:2020-02-21

Veranstaltungsbericht – Rückblick auf die Summer School für Gynäkologie und Geburtshilfe an der Universitätsfrauenklinik Erlangen - Zahn, Anna; Titzmann, Adriana; Pontones, Constanza (Geburtshilfe und Frauenheilkunde, 2022)
CRIS-Team WoS Importer:2022-11-04

Villoglandular adenocarcinoma of the uterine cervix: a systematic review and meta-analysis - Dietl, Anna; Beckmann, Matthias; Aumann, Konrad (Archives of Gynecology and Obstetrics, 2021)
Purpose: Villoglandular adenocarcinoma (VGA) of the uterine cervix has been classified as a rare subtype of cervical adenocarcinoma with good prognosis. A conservative surgical approach is considered feasible. The main risk factor is the presence of other histologic types of cancer. In this largest systematic review to date, we assess oncological outcomes associated with conservative therapy compared to those associated with invasive management in the treatment of stage Ia and Ib1 VGA. Methods: Case series and case reports identified by searching the PubMed database were eligible for inclusion in this review (stage Ia–Ib1). Results: A total of 271 patients were included in our literature review. 54 (20%) patients were treated by “conservative management” (conization, simple hysterectomy, and trachelectomy) and 217 (80%) by “invasive management” (radical hysterectomy ± radiation, hysterectomy, and radiation). Recurrences of disease (RODs) were found in the conservative group in two (4%) cases and in the invasive group in nine (4%) cases. There was no significant difference in disease-free survival (DFS) according to conservative or invasive treatment (p = 0.75). The histology of VGA may be complex with underlying usual adenocarcinoma (UAC) combined with VGA. Conclusion: The excellent prognosis of pure VGA and the young age of the patients may justify the management of this tumor using a less radical procedure. The histological diagnosis of VGA is a challenge, and pretreatment should not be based solely on a simple punch biopsy but rather a conization with wide tumor-free margins.
CRIS-Team Scopus Importer:2021-06-04
Keywords: Cervix; Conservative therapy; Invasive therapy; Review; Villoglandular adenocarcinoma

VILLOGLANDULAR ADENOCARCINOMA OF THE UTERINE CERVIX: SUPPORT FOR LESS INVASIVE MANAGEMENT - Dietl, Anna; Aumann, K. (INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2019)
CRIS-Team WoS Importer:2020-04-24

Virilizing Hilus Cell Tumor of the Ovary Associated With Efferent Ductules-like Metaplasia Within Paratubal Mesonephric Remnants - Wachter, David; Burghaus, Stefanie; Beckmann, Matthias; Agaimy, Abbas (International Journal of Gynecological Pathology, 2016)
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Vitamin B-Can it prevent cognitive decline? A systematic review and meta-analysis - Behrens, Annika; Grässel, Elmar; Pendergrass, Anna; Donath, Carolin (Systematic Reviews, 2020)
BACKGROUND: Development of cognitive decline represents substantial issues in today's society, steadily gaining importance with increasing life expectancy. One potential approach to preventing cognitive decline is to lower homocysteine by administering vitamin B. In this systematic review and meta-analysis, we address this topic and investigate whether oral supplementation of vitamin B can successfully prevent cognitive decline in cognitively unimpaired individuals. METHODS: A computerized systematic literature search was conducted using the electronic databases PubMed, Embase, and the Cochrane Library. Eligibility criteria included oral supplementation with vitamin B (B1, B6, folic acid, and B12) and the absence of cognitive impairment. A meta-analysis was conducted with "global cognition" as the primary outcome of this review. Secondary outcomes were changes in cognitive function in other cognitive domains reported in the included studies. Risk of bias was assessed according to the Cochrane Risk of Bias tool and the GRADE approach to establish the overall certainty of the evidence. RESULTS: The meta-analysis did not yield a significant overall effect of supplementation with vitamin B on cognitive function (Z = 0.87; p = 0.39; SMD, 0.02; 95% CI, - 0.034, 0.08). A sensitivity analysis focusing on specific risk factors did not alter this result. Some studies reported isolated significant effects of the intervention on secondary outcomes. However, these findings were outnumbered by the number of cognitive tests that did not yield significant effects. DISCUSSION: We found no overall evidence that oral vitamin B supplementation prevented cognitive decline. The isolated significant effects that were reported could be attributed to methodological issues. The results of this review do not provide evidence that population groups with certain risk factors would profit more from the intervention than others. Our findings do not apply to forms of administration other than oral supplementation nor do they offer information regarding the treatment of cognitively impaired individuals via the administration of vitamin B. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017071692.
CRIS-Team Scopus Importer:2020-05-29
Keywords: Cognition[Mesh]; Dementia[Mesh]; Folic Acid[Mesh]; Prevention; Vitamin B12[Mesh]; Vitamin B6[Mesh]

Vitamine und Spurenelemente - Hack, Carolin; Wasner, Sonja (Gynäkologe, 2020)
Food supplements are becoming more and more popular these days. Both patients and healthy persons take them in order to achieve, among other things, an improvement in the quality of life. Whether this really makes sense is examined more closely in this article. A detailed overview of the vitamins and the most important trace elements is also given. Although micronutrients do not provide the body with energy, they must still be supplied. It is most sensible to supply all necessary vitamins and trace elements through food. In healthy persons with a balanced diet, no supplementation of micronutrients is necessary; however, in cases of deficiency, such as oncological patients, an external supply is necessary. In cancer patients, for example, a sufficient supply of vitamin C and D should be ensured, if necessary, also via food supplements. The current data situation shows, however, that an excessive supply can sometimes even result in the opposite effect. For example, it has been shown that an excessive intake of vitamin B12 can increase the risk of bronchial carcinoma. Likewise, no recommendation for the supplementation of selenium can be given at present from an oncological perspective. An exact overview of the current data situation is given in this article.
CRIS-Team Scopus Importer:2020-12-25
Keywords: Diet; Dietary supplements; Micronutrients; Quality of life; Selenium

Volume Quantification of the Thyroid Gland Using 3-D Ultrasound Imaging - Kollorz, Eva Nicole Karin; Hahn, Dieter; Grunewald, Markus; Goecke, Tamme W.; Hornegger, Joachim; Kuwert, Torsten (Nuklearmedizin Kongressausgabe 02/07, 2007)

What do patients want to know about contraception and which method would they prefer? - Oppelt, Patricia; Baier, Friederike; Fahlbusch, Christine; Heusinger, Katharina; Hildebrandt, Thomas; Breuel, Christiane; Dittrich, Ralf (Archives of Gynecology and Obstetrics, 2017)
PURPOSE: The aim of this study was to determine the extent to which women's choice of contraceptive method depends on the advice received from their gynecologist and whether more intensive counseling might lead to more frequent use of long-acting reversible contraception (LARC). METHODS: A total of 1089 physicians and 18,521 women responded to 32 or 37 questions, respectively, using an online questionnaire. The women were asked about their current use of contraceptive methods, the extent of their satisfaction with them, their satisfaction with the counseling they had received, and whether they wanted to have more information about contraception. The physicians were similarly asked which contraceptive methods were being used, how satisfied with them they were, how they would assess their patients' satisfaction with them, and whether the women wanted to have more information. RESULT: The results showed that 61% of the women were using oral contraceptives, and a total of only 9% were using behavior-independent long-term contraceptive methods. However, 60% of the women stated that long-term contraception would be an option for them if they had more information about it. Gynecologists underestimated this figure, at only 18%. Whereas 66% of the gynecologists believed that their patients never forgot to take the pill, nearly, half of the women stated that they had forgotten it at least once during the previous 3 months. CONCLUSION: The small number of women who use long-term contraception is in clear contrast to the fact that many women want to have a very safe but also behavior-independent method.
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When sex is not on fire: a prospective multicentre study evaluating the short-term effects of radical resection of endometriosis on quality of sex life and dyspareunia - Fritzer, Nadja; Tammaa, Ayman; Haas, Dietmar; Oppelt, Peter; Renner, Stefan; Hornung, Daniela; Woelfler, Monika; Ulrich, Uwe; Hudelist, Gernot (European Journal of Obstetrics Gynecology and Reproductive Biology, 2016)
OBJECTIVE: The aim of the current study was to evaluate the effect of surgical removal of endometriosis on dyspareunia, sexual function, quality of sex life and interpersonal relationships. STUDY DESIGN: A questionnaire-based multicentre prospective study was conducted in six tertiary referral centres in Austria and Germany. Ninety-six patients with histologically proven endometriosis and dyspareunia were included. Before surgery and averagely 10 months postoperatively (range 9-12 months), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale (FSDS) were used to screen women's sexuality. Additionally, we evaluated psychological parameters and pain intensity during/after sexual intercourse via a self-administered questionnaire. RESULTS: Pain scores measured via NAS during/after intercourse decreased significantly after surgery. Frequencies of interrupted sexual intercourse, feelings of guilt towards the partner, being afraid of pain before/during sexual intercourse and feelings of being a burden for the relationship also decreased significantly in patients with peritoneal endometriosis and deep infiltrating endometriosis. Interestingly, sexually related personal distress did not improve in women with peritoneal endometriosis/vaginal resection, but improved in cases of deep infiltrating endometriosis (DIE). CONCLUSION: Radical laparoscopic excision of endometriosis offers an effective treatment option and offers a significant improvement in dyspareunia and quality of sex life.
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When to treat the pelvis in node-positive vulvar cancer: Results from the AGO-VOP.2 QS vulva study - Hampl, M.; Jaeger, A.; Eulenburg, C.; Prieske, K.; Hambrecht, J.; Fuerst, S.; Klapdor, R.; Heublein, S.; Gaß, Paul; Rohner, A.; Canzler, U.; Becker, S.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-12-23

Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients - Alunni-Fabbroni, Marianna; Majunke, Leonie; Trapp, Elisabeth K.; Tzschaschel, Marie; Mahner, Sven; Fasching, Peter; Fehm, Tanja; Schneeweiss, Andreas; Beck, Thomas; Lorenz, Ralf; Friedl, Thomas W. P.; Janni, Wolfgang; et al. (BMC Cancer, 2018)
microRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting.A total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, -19a, - 21, - 22, -20a, - 127, - 155, -200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests.In our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients' clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels.This pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.
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Whole-Body Electromyostimulation combined with personalized Nutritional Support improves the Body Composition of Patients with advanced Cancer - Schink, Kristin; Herrmann, Hans Joachim; Schwappacher, Raphaela; Orlemann, Till; Meyer, Julia; Waldmann, Elisabeth; Wullich, Bernd; Kahlmeyer, Andreas; Fietkau, Rainer; Lubgan, Dorota; Beckmann, Matthias; Hack, Carolin; et al. (2018)
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Willingness of Patients with Breast Cancer in the Adjuvant and Metastatic Setting to Use Electronic Surveys (ePRO) Depends on Sociodemographic Factors, Health-related Quality of Life, Disease Status and Computer Skills - Graf, Joachim; Simoes, E.; Wisslicen, K.; Rava, L.; Walter, C. B.; Hartkopf, A.; Keilmann, L.; Taran, A.; Wallwiener, S.; Fasching, Peter; Brucker, S. Y.; Wallwiener, M. (Geburtshilfe und Frauenheilkunde, 2016)
Introduction: Because of the often unfavorable prognosis, particularly for patients with metastases, health-related quality of life is extremely important for breast cancer patients. In recent years, data on patient-relevant endpoints is being increasingly collected electronically; however, knowledge on the acceptance and practicability of, and barriers to, this form of data collection remains limited.Material and Methods:A questionnaire was completed by 96 patients to determine to what extent existing computer skills, disease status, health-related quality of life and sociodemographic factors affect patients' potential willingness to use electronics methods of data collection (ePRO).Results:52 of 96 (55 %) patients reported a priori that they could envisage using ePRO. Patients who a priori preferred a paper-based survey (pPRO) tended to be older (ePRO 53 years vs. pPRO 62 years; p = 0.0014) and typically had lower levels of education (p = 0.0002), were in poorer health (p = 0.0327) and had fewer computer skills (p = 0.0003).Conclusion:Barriers to the prospective use of ePRO were identified in older patients and patients with a lower quality of life. Given the appropriate conditions with regard to age, education and current health status, opportunities to participate should be provided to encourage patients' willingness to take part and ensure the validity of survey results. Focusing on ease of use of ePRO applications and making applications more patient-oriented and straightforward appears to be the way forward.
EVALuna2:33539

„Wind of change“ - Kehl, Sven (Zeitschrift für Geburtshilfe und Neonatologie, 2023)
CRIS-Team Scopus Importer:2023-04-28

Xenotransplantation of cryopreserved human ovarian tissue - a systematic review of MII oocyte maturation and discussion of it as a realistic option for restoring fertility after cancer treatment - Dittrich, Ralf; Lotz, Laura; Fehm, Tanja; Kruessel, Jan; Von Wolff, Michael; Toth, Bettina; Van Der Ven, Hans; Schuering, Andreas N.; Wuerfel, Wolfgang; Hoffmann, Inge; Beckmann, Matthias (Fertility and Sterility, 2015)
To systematically review the reporting of MII (MII) oocyte development after xenotransplantation of human ovarian tissue.Systematic review in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).Not applicable.Not applicable.Formation of MII oocytes after xenotransplantation of human ovarian tissue.Any outcome reported in Pubmed.Six publications were identified that report on formation of MII oocytes after xenotransplantation of human ovarian tissue.Xenografting of human ovarian tissue has proved to be a useful model for examining ovarian function and follicle development in vivo. With human follicles that have matured through xenografting, the possibility of cancer transmission and relapse can also be eliminated, because cancer cells are not able to penetrate the zona pellucida. The reported studies have demonstrated that xenografted ovarian tissue from a range of species, including humans, can produce antral follicles that contain mature (MII) oocytes, and it has been shown that mice oocytes have the potential to give rise to live young. Although some ethical questions remain unresolved, xenotransplantation may be a promising method for restoring fertility. This review furthermore describes the value of xenotransplantation as a tool in reproductive biology and discusses the ethical and potential safety issues regarding ovarian tissue xenotransplantation as a means of recovering fertility.
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Zoledronate for patients with invasive residual disease after anthracyclines-taxane-based chemotherapy for early breast cancer - The Phase III NeoAdjuvant Trial Add-oN (NaTaN) study (GBG 36/ABCSG 29) - Von Minckwitz, G.; Rezai, M.; Tesch, H.; Huober, J.; Gerber, B.; Zahm, D. M.; Hilfrich, J.; Costa, S. D.; Dubsky, P.; Blohmer, J. U.; Denkert, Carsten; Hanusch, C.; et al. (European Journal of Cancer, 2016)
BACKGROUND: Patients with invasive residual disease after neoadjuvant chemotherapy (NACT) are considered to have chemo-resistant breast cancer. Bisphosphonates are an established treatment for bone metastases and are of potential benefit as adjuvant treatment in early breast cancer. PATIENTS AND METHODS: Patients who had invasive tumour residuals (ypT1-4 and/or ypN+) after a minimum of four cycles of anthracycline-taxane-containing NACT were eligible for the NeoAdjuvant Trial Add-oN study. Patients were randomised within 3 years after surgery to receive zoledronate 4 mg i.v. for 5 years versus observation. Zoledronate was given every 4 weeks for the first 6 months, every 3 months for the following 2 years, and every 6 months for the last 2.5 years. Primary objective was disease-free survival. RESULTS: After a median time of 54.7 months no difference in disease-free survival was observed between the zoledronate and observation groups (hazard ratio [HR] 0.960, 95% confidence interval [CI] 0.709-1.30, log rank P=0.789). Various subgroups were examined without identifying a treatment effect of zoledronate. Patients over 55 years of age showed a HR of 0.832 in favour of zoledronate, but the result was not significant (P=0.480). A similar result was obtained for overall survival with a HR of 1.19 (95% CI 0.79-1.79; log rank P=0.408). Zoledronate was well tolerated and no new toxicity signal was identified. CONCLUSION: Postneoadjuvant treatment with zoledronate does not improve outcome in patients without pathological complete response after neoadjuvant anthracycline-taxane-based chemotherapy for early breast cancer.
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Zukunft mammographie-basierter Bildgebung [Future of mammography-based imaging] - Schulz-Wendtland, Rüdiger; Wittenberg, Thomas; Michel, Thilo; Hartmann, Arndt; Beckmann, Matthias; Rauh, Claudia; Judt, Sebastian; Brehm, Barbara; Meier-Meitinger, Martina; Anton, Gisela; Uder, Michael; Fasching, Peter (Radiologe, 2014)
Mammography is the central diagnostic method for clinical diagnostics of breast cancer and the breast cancer screening program. In the clinical routine complementary methods, such as ultrasound, tomosynthesis and optional magnetic resonance imaging (MRI) are already combined for the diagnostic procedure. Future developments will utilize investigative procedures either as a hybrid (combination of several different imaging modalities in one instrument) or as a fusion method (the technical fusion of two or more of these methods) to implement fusion imaging into diagnostic algorithms. For screening there are reasonable hypotheses to aim for studies that individualize the diagnostic process within the screening procedure. Individual breast cancer risk prediction and individualized knowledge about sensitivity and specificity for certain diagnostic methods could be tested. The clinical implementation of these algorithms is not yet in sight. (orig.) [German] Die Mammographie ist die zentrale diagnostische Methode der klinischen symptombezogenen Abklaerung von Brusterkrankungen und des Brustkrebsscreenings. In der klinischen Diagnostik wird sie heute schon oft durch zusaetzliche Untersuchungsmethoden wie dem Ultraschall, der Tomosynthese und ggf. auch der MRT-Bildgebung unterstuetzt. Zukuenftige Entwicklungen gehen in die Richtung, dass diese Kombination aus 2 oder mehr Untersuchungsverfahren entweder in Hybrid- (Aufnahme mehrerer unterschiedlicher Bildmodalitaeten in einem einzigen Geraet) oder in Fusionsmethoden (Zusammenfuehrung und Registrierung von Bilddaten aus verschiedenen Modalitaeten) technisch professionalisiert werden. Des Weiteren koennten an subgruppenbezogene Erkrankungsrisiken und individuelle Sensitivitaeten und Spezifitaeten angepasste Diagnostikkombinationen fuer eine Screeningdiagnostik Gegenstand kuenftiger Studien sein. Wir stellen die aktuellen Entwicklungen auf diesen Gebieten und deren momentane Relevanz fuer die klinische Praxis und Entwicklungspotenzial fuer die Zukunft dar. (orig
UnivIS-Import:2015-04-14:Pub.2014.tech.IMMD.IMMD9.zukunf
Keywords: MAMMOgraphy

Body Image and Sexual Desire in the Context of Gender Affirming Therapy: Results of a Cross-sectional Multi-centered Transgender Study - Garz, Maria; Schröder, Johanna; Nieder, Timo; Becker, Inga; Biedermann, Sarah; Hildebrandt, Thomas; Briken, Peer; Auer, Matthias; Fuβ, Johannes (Journal of Sex & Marital Therapy, 2021)
It has been posited that gender-affirming treatment (GAT) can have an influence on body image and sexual desire in trans people. This study aims to examine associations between GAT and sexual desire as well as whether body image mediates the influences of gender-affirming hormone therapy (GAHT) or gender-affirming surgery (GAS) on sexual desire. A total of 210 individuals diagnosed with gender dysphoria (n = 105 of each gender) were assessed via self-assessment questionnaires in a cross-sectional study. Associations between GAT and sexual desire were investigated via multivariate analyses of variance. Mediation analyses were conducted to clarify associations between GAHT/GAS, body image, and sexual desire. GAHT was associated with increased sexual desire only in transmen. GAS had no significant effect on sexual desire in transmen and transwomen. Body image did not mediate the influence of GAHT or GAS on sexual desire in both groups. GAHT and GAS had significant direct effects on body image in both genders, whereas body image showed no significant direct effect on sexual desire. The results indicate that effects of GAT on sexual desire seem to be attributable to other factors than body image, such as the hormonal influence of testosterone in transmen.
CRIS-Team Scopus Importer:2021-03-05
Keywords: gender dysphoria; gender incongruence; Transgender; transsexualism

Event Report 3rd Symposium of the AGO Commission Integrative Medicine - Hack, Carolin (Geburtshilfe und Frauenheilkunde, 2017)
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Help Shape Training - Gabriel, Lena; Lermann, Johannes; Schott, Sarah; Puppe, Julian (Geburtshilfe und Frauenheilkunde, 2016)
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Hormonal Contraception. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry Number 015/015, January 2020) - Franik, Sebastian; Bauersachs, Rupert; Beyer-Westendorf, Jan; Buchholz, Tina; Bühling, Kai; Diener, Hans Christoph; Erath, Anke; Fischer, Ronald; Förderreuther, Stefanie; Franz, Heiko B.G.; Hach-Wunderle, Viola; Hadji, Peymann; et al. (Geburtshilfe und Frauenheilkunde, 2021)
Aims This is an official interdisciplinary guideline published and coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking regions and is backed by numerous professional societies and organizations. The aim of this guideline is to provide an evidence- and consensus-based overview of the diagnostic approach and the management of hormonal contraception based on a systematic evaluation of the relevant literature. Methods To compile this S3-guideline, a systematic search for evidence was carried out in PubMed and the Cochrane Library to adapt existing guidelines and identify relevant reviews and meta-analyses. A structured evaluation of the evidence was subsequently carried out on behalf of the Guidelines Commission of the DGGG, and a structured consensus was achieved based on consensus conferences attended by representative members from the different specialist societies and professions. Recommendations Evidence-based recommendations about the advice given to women requesting contraception were compiled. The guideline particularly focuses on prescribing contraceptives which are appropriate to women's individual needs, take account of her personal circumstances, and have few or no side effects.
CRIS-Team Scopus Importer:2021-02-26
Keywords: counseling; guideline; hormonal contraception; recommendations

Lymph node ratio in inguinal lymphadenectomy for squamous cell vulvar cancer: Results from the AGO-CaRE-1 study - Polterauer, Stephan; Schwameis, Richard; Grimm, Christoph; Hillemanns, Peter; Jückstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Hasenburg, Annette; Sehouli, Jalid; Fürst, Sophie Theresa; Strauß, Hans Georg; Baumann, Klaus; et al. (Gynecologic Oncology, 2019)
Objective: Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project. Methods: The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival. Results: In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of >0% < 20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (P < .001), advanced tumor stage (P < .001), high tumor grade (P < .001), and deep stromal invasion (P < .001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%, >0% < 20%, and ≥20%, respectively (P < .001, P < .001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01–14.98, P < .001), FIGO stage (HR 1.41, 95%-CI 1.18–1.69, P < .001), and patient's performance status (HR 1.59, 95%-CI 1.39–1.82, P < .001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64–28.78, P < .001), and performance status (HR 1.72, 95%-CI 1.44–2.07, P < .001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models. Conclusions: In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.
CRIS-Team Scopus Importer:2019-05-02
Keywords: Cancer prognosis; Cancer recurrence; Lymph node metastases; Lymph node ratio; Vulvar cancer

Temsirolimus in women with platinum-refractory/resistant ovarian cancer or advanced/recurrent endometrial carcinoma. A phase II study of the AGO-study group (AGO-GYN8) - Emons, Guenter; Kurzeder, Christian; Schmalfeldt, Barbara; Neuser, Petra; De Gregorio, Nikolaus; Pfisterer, Jacobus; Park-Simon, Tjoung-Won; Mahner, Sven; Schroeder, Willibald; Lueck, Hans-Joachim; Heubner, Martin Leonhard; Hanker, Lars; et al. (Gynecologic Oncology, 2016)
OBJECTIVES: To evaluate activity and toxicity of mTOR inhibitor temsirolimus in patients with platinum-refractory/resistant ovarian cancer (OC) or advanced/recurrent endometrial carcinoma (EC). METHODS: Women with epithelial ovarian, fallopian tube or primary peritoneal cancer were eligible, when they had progression during treatment with a platinum based regimen or within 6 months after receiving a platinum based regimen and a previous taxane treatment. Women with advanced/recurrent EC, no longer amenable to curative surgery and/or radiotherapy were eligible when they had no previous or only adjuvant chemotherapy. Preceding endocrine therapy for metastatic/recurrent disease was allowed. Patients received weekly IV infusions of 25mg temsirolimus. Primary endpoint was progression free survival rate after 4 months (OC) or 6 months (EC). A two stage design was applied. RESULTS: Forty-four patients (OC: n=22; EC: n=22) were enrolled and received temsirolimus treatment. Median age was 56 years (OC) or 63 years (EC). After eight weeks of treatment, 10 of 21 evaluable patients in the OC cohort and 8 of 20 evaluable patients in the EC cohort had progressive disease. Thus efficacy did not meet the predefined levels during the first stage of recruitment and the trial was stopped. Some patients in both cohorts had long lasting PFS (>7 months). Toxicity of temsirolimus was mild. CONCLUSIONS: Temsirolimus treatment was well tolerated in our patients, but did not meet the predefined efficacy criteria. In our study as in other trials on rapalogs in OC or EC, a few patients had long lasting disease stabilisations.
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