Permacol collagen paste for cryptoglandular and Crohn's anal fistula - Brunner, Michaela; Schneider, Ignaz Hans Friedrich; Guenther, K.; Grützmann, Robert; Matzel, Klaus (Techniques in Coloproctology, 2019)
BackgroundPermacol collagen paste, an acellular crosslinked porcine dermal collagen matrix suspension, is a new treatment option for anal fistula. Data remain limited, however, and as yet only the results of one case of Crohn's fistula treated with Permacol paste has been reported. The aim of this study was to assess the use of Permacol collagen paste in patients with cryptoglandular and Crohn's perianal fistulae.MethodsA prospective study was conducted on patients with anal fistula, treated with Permacol paste. Patients were followed at 1week, 6 and 12months, and on demand thereafter. The main focus was on fistula healing and postoperative continence. The former was defined as the absence of signs of recurrence on clinical examination, proctoscopy and rigid rectoscopy. Fecal incontinence was assessed before surgery and at each follow-up.ResultsThirty patients (19 women, 11 men; mean age 46years), 12 (40%) of whom had Crohn's disease were included. The average number of previous fistula operations was 6. All patients had 6months of follow-up, and 24 patients (80%) had 12months of follow-up. The healing rate in all patients was 57% (17 of 30 patients) at 6months and 63% (15 of 24 patients) at 12months. One patient reported a worsening of fecal incontinence at 12 months; 2 patients had adverse events (perianal pain: n=1, fluid accumulation n=1) requiring fistula drainage. Patient characteristics, healing, incontinence, and adverse events did not differ significantly between patients with and without Crohn's disease.ConclusionsOur data indicate that Permacol paste is a safe and moderately effective treatment for cryptoglandular and Crohn's fistulae.
CRIS-Team WoS Importer:2019-04-12

Perspectives of patients and clinicians on big data and AI in health: a comparative empirical investigation - Hummel, Patrik; Braun, Matthias; Bischoff, Serena; Samhammer, David; Seitz, Katharina; Fasching, Peter; Dabrock, Peter (AI and Society, 2024)
Background: Big data and AI applications now play a major role in many health contexts. Much research has already been conducted on ethical and social challenges associated with these technologies. Likewise, there are already some studies that investigate empirically which values and attitudes play a role in connection with their design and implementation. What is still in its infancy, however, is the comparative investigation of the perspectives of different stakeholders. Methods: To explore this issue in a multi-faceted manner, we conducted semi-structured interviews as well as focus group discussions with patients and clinicians. These empirical methods were used to gather interviewee’s views on the opportunities and challenges of medical AI and other data-intensive applications. Results: Different clinician and patient groups are exposed to medical AI to differing degrees. Interviewees expect and demand that the purposes of data processing accord with patient preferences, and that data are put to effective use to generate social value. One central result is the shared tendency of clinicians and patients to maintain individualistic ascriptions of responsibility for clinical outcomes. Conclusions: Medical AI and the proliferation of data with import for health-related inferences shape and partially reconfigure stakeholder expectations of how these technologies relate to the decision-making of human agents. Intuitions about individual responsibility for clinical outcomes could eventually be disrupted by the increasing sophistication of data-intensive and AI-driven clinical tools. Besides individual responsibility, systemic governance will be key to promote alignment with stakeholder expectations in AI-driven and data-intensive health settings.
CRIS-Team Scopus Importer:2024-01-12
Keywords: Big data; Ethics; Health; Interviews; Privacy; Self-determination; Stakeholder

Phase III post-neoadjuvant study evaluating sacituzumab govitecan (SG), an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment: SASCIA - Marme, F.; Hanusch, C.; Furlanetto, J.; Denkert, C.; Link, T.; Untch, M.; Blohmer, J-U.; Jackisch, C.; Reinisch, M.; Rhiem, K. E.; Schneeweiss, A.; Solbach, C.; et al. (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-10-15

Phase III Randomized Study of Ribociclib and Fulvestrant in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: MONALEESA-3 - Slamon, Dennis J.; Neven, Patrick; Chia, Stephen; Fasching, Peter; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia Val; Esteva, Francisco J.; Martin, Miguel; Nusch, Arnd; Sonke, Gabe S.; et al. (Journal of Clinical Oncology, 2018)
Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.
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Phase II neoadjuvant study of GDC-9545+palbociclib (palbo) vs anastrozole (A) plus palbo in postmenopausal women with estrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2-eBC) - Hurvitz, Sara A.; Fasching, Peter; Park, Yeon Hee; Quiroga, Vanesa; Crnjevic, Tanja Badovinac; Fresco, Rodrigo; Lopez-Valverde, Vanesa; Steinseifer, Jutta; Ye, Chenglin; Bardia, Aditya (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

pH dependence of the decomposition behavior of urogynecological fixation materials - Keckstein, P.; Lotz, Laura; Palmisano, Ralf; Hübner, Sabine; Apeleo Zubiri, Benjamin; Spiecker, Erdmann; Burghaus, Stefanie; Beckmann, Matthias; Hoeffmann,; Dittrich, Ralf; Hein, Alexander; Lermann, Johannes (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

PHIP - a novel candidate breast cancer susceptibility locus on 6q14.1 - Jiao, Xiang; Aravidis, Christos; Marikkannu, Rajeshwari; Rantala, Johanna; Picelli, Simone; Adamovic, Tatjana; Liu, Tao; Maguire, Paula; Kremeyer, Barbara; Luo, Liping; Von Holst, Susanna; Kontham, Vinaykumar; et al. (Oncotarget, 2017)
Most non-BRCA1/2 breast cancer families have no identified genetic cause. We used linkage and haplotype analyses in familial and sporadic breast cancer cases to identify a susceptibility locus on chromosome 6q. Two independent genome-wide linkage analysis studies suggested a 3 Mb locus on chromosome 6q and two unrelated Swedish families with a LOD >2 together seemed to share a haplotype in 6q14.1. We hypothesized that this region harbored a rare high-risk founder allele contributing to breast cancer in these two families. Sequencing of DNA and RNA from the two families did not detect any pathogenic mutations. Finally, 29 SNPs in the region were analyzed in 44,214 cases and 43,532 controls from BCAC, and the original haplotypes in the two families were suggested as low-risk alleles for European and Swedish women specifically. There was also some support for one additional independent moderate-risk allele in Swedish familial samples. The results were consistent with our previous findings in familial breast cancer and supported a breast cancer susceptibility locus at 6q14.1 around the PHIP gene.
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PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer - Loibl, Sibylle; Von Minckwitz, Gunter; Schneeweiss, Andreas; Paepke, Stefan; Lehmann, Annika; Rezai, Mahdi; Zahm, Dirk M.; Sinn, Peter; Khandan, Fariba; Eidtmann, Holger; Dohnal, Karel; Heinrichs, Clemens; et al. (Journal of Clinical Oncology, 2014)
Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in breast cancer, with mutations in PIK3CA being the most common. This study investigated the association between PIK3CA genotype and pathologic complete response (pCR) rates in human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with either dual or single anti-HER2 treatment in addition to neoadjuvant chemotherapy.PIK3CA mutations in 504 tumor samples from participants in the neoadjuvant GeparQuattro, GeparQuinto, and GeparSixto studies were evaluated. All HER2-positive patients received either trastuzumab or lapatinib or the combination plus anthracycline-taxane chemotherapy. PIK3CA mutations were evaluated in formalin-fixed, paraffin-embedded tissues from core biopsies with a tumor cell content of >= 20% by using classical Sanger sequencing of exon 9 and exon 20.Overall, 21.4% of the patients harbored a PIK3CA mutation. Detection of a PIK3CA mutation was significantly associated with a lower pCR rate (19.4% with PIK3CA mutation v 32.8% with PIK3CA wild-type; odds ratio [OR], 0.49; 95% CI, 0.29 to 0.83; P = .008). In the 291 hormone receptor (HR) -positive tumors, pCR rate was 11.3% with a PIK3CA mutation compared with 27.5% with PIK3CA wild-type (OR, 0.34; 95% CI, 0.15 to 0.78; P = .011). In 213 patients with HR-negative tumors, pCR rate was 30.4% with PIK3CA mutation and 40.1% without (OR, 0.65; 95% CI, 0.32 to 1.32; P = .233; interaction test P = .292). In multivariable analysis, HR status and PIK3CA status provided independent predictive information. In patients with PIK3CA mutation, the pCR rates were 16%, 24.3%, and 17.4% with lapatinib, trastuzumab, and the combination, respectively (P = .654) and in the wild-type group, they were 18.2%, 33.%, and 37.1%, respectively (P = .017). Disease-free survival and overall survival were not statistically significantly different between patients with mutant and wild-type PIK3CA.HER2-positive breast carcinomas with a PIK3CA mutation are less likely to achieve a pCR after neoadjuvant anthracycline-taxane-based chemotherapy plus anti-HER2 treatment, even if a dual anti-HER2 treatment is given.
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Piwi-like 1 and piwi-like 2 expression in breast cancer - Erber, Ramona; Meyer, Julia; Taubert, Helge; Fasching, Peter; Wach, Sven; Häberle, Lothar; Gaß, Paul; Schulz-Wendtland, Rüdiger; Landgraf, Laura; Olbricht, Sabrina; Jung, Rudolf; Beckmann, Matthias; et al. (Cancers, 2020)
PIWI-like 1 and PIWI-like 2 play a role in stem cell self-renewal, and enhanced expression has been reported for several tumor entities. However, few studies have investigated PIWI-like 1 and PIWI-like 2 expressions in breast cancer subtypes regarding prognosis. Therefore, we examined protein expression in a large consecutive cohort of breast cancer patients and correlated it to breast cancer subtypes and survival outcome. PIWI-like 1 and PIWI-like 2 expressions were evaluated using immunohistochemistry in a cohort of 894 breast cancer patients, of whom 363 were eligible for further analysis. Percentage and intensity of stained tumor cells were analyzed and an immunoreactive score (IRS) was calculated. The interaction of PIWI-like 1 and PIWI-like 2 showed a prognostic effect on survival. For the combination of high PIWI-like 1 and low PIWI-like 2 expressions, adjusted hazard ratios (HRs) were significantly higher with regard to overall survival (OS) (HR 2.92; 95% confidence interval (CI) 1.24, 6.90), disease-free survival (DFS) (HR 3.27; 95% CI 1.48, 7.20), and distant disease-free survival (DDFS) (HR 7.64; 95% CI 2.35, 24.82). Both proteins were significantly associated with molecular-like and PAM50 subgroups. Combining high PIWI-like 1 and low PIWI-like 2 expressions predicted poorer prognosis and both markers were associated with aggressive molecular subtypes.
CRIS-Team Scopus Importer:2020-11-20
Keywords: Breast cancer; HER2; Luminal A; Luminal B; Molecular breast cancer subtypes; PIWI-like 1; PIWI-like 2; PIWIL1; PIWIL2; TNBC

Plasticity of patient-matched normal mammary epithelial cells is dependent on autologous adipose-derived stem cells - Kengelbach-Weigand, Annika; Tasbihi, Kereshmeh; Strissel, Pamela; Schmid, Rafael; Marques, Jasmin Monteiro; Beier, Justus; Beckmann, Matthias; Strick, Reiner; Horch, Raymund E.; Boos, Anja (Scientific Reports, 2019)
Due to the increasing clinical application of adipose-derived stem cells (ADSC), e.g. lipotransfer for breast reconstruction, this study aimed to gain novel insights regarding ADSC influence on breast tissue remodeling and determine patient-dependent factors affecting lipotransfer as well as begin to address its oncological risks. The ADSC secretome was analyzed from five normal breast reduction patients and contained elevated levels of growth factors, cytokines and proteins mediating invasion. ADSC/ADSC secretomes were tested for their influence on the function of primary mammary epithelial cells, and tumor epithelial cells using cell culture assays. ADSC/ADSC secretomes significantly stimulated proliferation, transmigration and 3D-invasion of primary normal and tumor epithelial cells. IL-6 significantly induced an EMT and invasion. The ADSC secretome significantly upregulated normal epithelial cell gene expression including MMPs and ECM receptors. Our study supports that ADSC and its secretome promote favorable conditions for normal breast tissue remodeling by changing the microenvironment. and may also be important regarding residual breast cancer cells following surgery.
CRIS-Team Scopus Importer:2019-08-06

PML-nuclear bodies decrease with age and their stress response is impaired in aged individuals - Wenger, Barbara; Schwegler, Manuela; Brunner, Michaela; Daniel, Christoph; Schmidt, Manfred; Fietkau, Rainer; Distel, Luitpold (BMC Geriatrics, 2014)
Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate differences in patients' PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age.In order to clarify the role of PML-NBs in the aging process, we examined peripheral blood monocytes of 134 cancer patients and 41 healthy individuals between 22 and 92 years of age, both before and after in vitro irradiation. Additionally, we analyzed the samples of the cancer patients after in vivo irradiation. Cells were immunostained and about 1600 cells per individual were analyzed for the presence of PML- and ?H2AX foci.The number of existing PML-NBs per nucleus declined with age, while the number of ?H2AX foci increased with age. There was a non-significant trend that in vivo irradiation increased the number of PML-NBs in cells of young study participants, while in older individuals PML-NBs tended to decrease. It can be assumed that PML-NBs decrease in number during the process of aging.The findings suggest that there is a dysfunctional PML-NBs stress response in aged cells.
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk - Dareng, Eileen O.; Tyrer, Jonathan P.; Barnes, Daniel R.; Jones, Michelle R.; Yang, Xin; Aben, Katja K. H.; Adank, Muriel A.; Agata, Simona; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Aravantinos, Gerasimos; et al. (European Journal of Human Genetics, 2022)
Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28-1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08-1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21-1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29-1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35-1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
CRIS-Team WoS Importer:2022-01-28

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes - Mavaddat, Nasim; Michailidou, Kyriaki; Dennis, Joe; Lush, Michael; Fachal, Laura; Lee, Andrew; Tyrer, Jonathan P.; Chen, Ting-Huei; Wang, Qin; Bolla, Manjeet K.; Yang, Xin; Adank, Muriel A.; et al. (American Journal of Human Genetics, 2019)
Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
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Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression - Darabi, Hatef; Mccue, Karen; Beesley, Jonathan; Michailidou, Kyriaki; Nord, Silje; Kar, Siddhartha; Humphreys, Keith; Thompson, Deborah; Ghoussaini, Maya; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; et al. (American Journal of Human Genetics, 2015)
Genome-wide association studies have identified SNPs near ZNF365 at 10q21.2 that are associated with both breast cancer risk and mammographic density. To identify the most likely causal SNPs, we fine mapped the association signal by genotyping 428 SNPs across the region in 89,050 European and 12,893 Asian case and control subjects from the Breast Cancer Association Consortium. We identified four independent sets of correlated, highly trait-associated variants (iCHAVs), three of which were located within ZNF365. The most strongly risk-associated SNP, rs10995201 in iCHAV1, showed clear evidence of association with both estrogen receptor (ER)-positive (OR = 0.85 [0.82-0.88]) and ER-negative (OR = 0.87 [0.82-0.91]) disease, and was also the SNP most strongly associated with percent mammographic density. iCHAV2 (lead SNP, chr10: 64,258,684:D) and iCHAV3 (lead SNP, rs7922449) were also associated with ER-positive (OR = 0.93 [0.91-0.95] and OR = 1.06 [1.03-1.09]) and ER-negative (OR = 0.95 [0.91-0.98] and OR = 1.08 [1.04-1.13]) disease. There was weaker evidence for iCHAV4, located 5' of ADO, associated only with ER-positive breast cancer (OR = 0.93 [0.90-0.96]). We found 12, 17, 18, and 2 candidate causal SNPs for breast cancer in iCHAVs 1-4, respectively. Chromosome conformation capture analysis showed that iCHAV2 interacts with the ZNF365 and NRBF2 (more than 600 kb away) promoters in normal and cancerous breast epithelial cells. Luciferase assays did not identify SNPs that affect transactivation of ZNF365, but identified a protective haplotype in iCHAV2, associated with silencing of the NRBF2 promoter, implicating this gene in the etiology of breast cancer.
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Polymorphisms in inflammation pathway genes and endometrial cancer risk - Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Doerk, Thilo; Goodman, Marc T.; Zheng, Ying; et al. (Cancer Epidemiology Biomarkers & Prevention, 2013)
Background: Experimental and epidemiologic evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods: To investigate this hypothesis, a two-stage study was carried out to evaluate single-nucleotide polymorphisms (SNP) in inflammatory pathway genes in association with endometrial cancer risk. In stage I, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage I SNPs significantly associated with endometrial cancer (P < 0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage II, which consisted of 10 additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results: Five of the 21 SNPs had significant allelic odds ratios (ORs) and 95% confidence intervals (CI) as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact statement: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. © 2012 American Association for Cancer Research.
CRIS-Team Scopus Importer:2021-07-19

Polymorphisms in the RANK/RANKL genes and their effect on bone specific prognosis in breast cancer patients - Hein, Alexander; Bayer, Christian M.; Schrauder, Michael G.; Haeberle, Lothar; Heusinger, Katharina; Strick, Reiner; Ruebner, Matthias; Lux, Michael P.; Renner, Stefan; Schulz-Wendtland, Rüdiger; Ekici, Arif Bülent; Hartmann, Arndt; et al. (BioMed Research International, 2014)
The receptor activator of NF-?B (RANK) pathway is involved in bone health as well as breast cancer (BC) pathogenesis and progression. Whereas the therapeutic implication of this pathway is established for the treatment of osteoporosis and bone metastases, the application in adjuvant BC is currently investigated. As genetic variants in this pathway have been described to influence bone health, aim of this study was the prognostic relevance of genetic variants in RANK and RANKL. Single nucleotide polymorphisms in RANK(L) (rs1054016/rs1805034/rs35211496) were genotyped and analyzed with regard to bone metastasis-free survival (BMFS), disease-free survival, and overall survival for a retrospective cohort of 1251 patients. Cox proportional hazard models were built to examine the prognostic influence in addition to commonly established prognostic factors. The SNP rs1054016 seems to influence BMFS. Patients with two minor alleles had a more favorable prognosis than patients with at least one common allele (HR 0.37 (95% CI: 0.17, 0.84)), whereas other outcome parameters remained unaffected. rs1805034 and rs35211496 had no prognostic relevance. The effect of rs1054016(RANKL) adds to the evidence that the RANK pathway plays a role in BC pathogenesis and progression with respect to BMFS, emphasizing the connection between BC and bone health.
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Pooled analysis of patient (pt)-reported outcomes (PROs) in the MONALEESA (ML)-2,-3, and-7 trials: Additional results and key subgroup findings - Fasching, Peter; Bardia, A.; Nusch, A.; Jerusalem, G.; Chan, A.; El Saghir, N. S.; Conejo, E. Alba; Im, S-A.; Janni, W.; Chandiwana, D.; Lanoue, B. R.; Thuerigen, A.; et al. (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-05-28

Pooled analysis of patient (pt)-reported quality of life (QOL) in the MONALEESA (ML)-2,-3, and-7 trials of ribociclib (RIB) plus endocrine therapy (ET) to treat hormone receptore-positive, HER2-negative (HR+/HER2L) advanced breast cancer (ABC) - Fasching, Peter; Bardia, A.; Nusch, A.; Jerusalem, G.; Chan, A.; El Saghir, N.; Alba, E.; Im, S-A.; Janni, W.; Chandiwana, D.; Lanoue, B.; Thuerigen, A.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-10-30

Pooled Analysis of the Prognostic Relevance of Circulating Tumor Cells in Primary Breast Cancer - Janni, Wolfgang J.; Rack, Brigitte; Terstappen, Leon W. M. M.; Pierga, Jean-Yves; Taran, Florin-Andrei; Fehm, Tanja; Hall, Carolyn; De Groot, Marco R.; Bidard, Francois-Clement; Friedl, Thomas W. P.; Fasching, Peter; Brucker, Sara Y.; et al. (Clinical Cancer Research, 2016)
PURPOSE: Although unequivocal evidence has shown the prognostic relevance of circulating tumor cells (CTC) in the peripheral blood of patients with metastatic breast cancer, less evidence is available for the prognostic relevance of CTCs at the time of primary diagnosis. EXPERIMENTAL DESIGN: We conducted a pooled analysis of individual data from 3,173 patients with nonmetastatic (stage I-III) breast cancer from five breast cancer institutions. The prevalence and numbers of CTCs were assessed at the time of primary diagnosis with the FDA-cleared CellSearch System (Janssen Diagnostics, LLC). Patient outcomes were analyzed using meta-analytic procedures, univariate log-rank tests, and multivariate Cox proportional hazard regression analyses. The median follow-up duration was 62.8 months. RESULTS: One or more CTCs were detected in 20.2% of the patients. CTC-positive patients had larger tumors, increased lymph node involvement, and a higher histologic tumor grade than did CTC-negative patients (all P < 0.002). Multivariate Cox regressions, which included tumor size, nodal status, histologic tumor grade, and hormone receptor and HER2 status, confirmed that the presence of CTCs was an independent prognostic factor for disease-free survival [HR, 1.82; 95% confidence interval (CI), 1.47-2.26], distant disease-free survival (HR, 1.89; 95% CI, 1.49-2.40), breast cancer-specific survival (HR, 2.04; 95% CI, 1.52-2.75), and overall survival (HR, 1.97; 95% CI, 1.51-2.59). CONCLUSIONS: In patients with primary breast cancer, the presence of CTCs was an independent predictor of poor disease-free, overall, breast cancer-specific, and distant disease-free survival. Clin Cancer Res; 22(10); 2583-93. ©2016 AACR.
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Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies - Salmen, Jessica; Neugebauer, Julia; Fasching, Peter; Häberle, Lothar; Huober, Jens; Woeckel, Achim; Rauh, Claudia; Schuetz, Florian; Weissenbacher, Tobias; Kost, Bernd; Stickeler, Elmar; Klar, Maximilian; et al. (Breast Cancer Research and Treatment, 2014)
The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.
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Population distribution of lifetime risk of ovarian cancer in the United States - Pearce, Celeste Leigh; Stram, Daniel O.; Ness, Roberta B.; Stram, Douglas A.; Roman, Lynda D.; Templeman, Claire; Lee, Alice W.; Menon, Usha; Fasching, Peter; Mcalpine, Jessica N.; Doherty, Jennifer A.; Modugno, Francesmary; et al. (Cancer Epidemiology Biomarkers & Prevention, 2015)
In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than this average.We have characterized the distribution of lifetime risk in the general population. Published data on the relative risks and their variances for five well-accepted risk and protective factors for ovarian cancer, oral contraceptive use, parity, tubal ligation, endometriosis, and first-degree family history of ovarian cancer in conjunction with a genetic risk score using genome-wide significant common, low penetrance variants were used. The joint distribution of these factors (i.e., risk/protective factor profiles) was derived using control data from four U.S. population-based studies, providing a broad representation of women in the United States.A total of 214 combinations of risk/protective factors were observed, and the lifetime risk estimates ranged from 0.35% [95% confidence interval (CI), 0.29-0.42] to 8.78% (95% CI, 7.10-10.9). Among women with lifetime risk ranging from 4% to 9%, 73% had no family history of ovarian cancer; most of these women had a self-reported history of endometriosis.Profiles including the known modifiable protective factors of oral contraceptive use and tubal ligation were associated with a lower lifetime risk of ovarian cancer. Oral contraceptive use and tubal ligation were essentially absent among the women at 4% to 9% lifetime risk.This work demonstrates that there are women in the general population who have a much higher than average lifetime risk of ovarian cancer. Preventive strategies are available. Should effective screening become available, higher than average risk women can be identified.
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Possible Rates of Detection of Neonatal Sepsis Pathogens in the Context of Microbiological Diagnostics in Mothers – Real World Data - Kuld, Raffael; Krauth, Alexander; Kühr, Joachim; Krämer, Janine; Dittrich, Ralf; Häberle, Lothar; Müller, Andreas (Geburtshilfe und Frauenheilkunde, 2023)
Objective The aim of this study was to identify the rate of detection of neonatal sepsis pathogens in maternal microbiological smears. Study Design This is a retrospective study conducted at a Level 1 perinatal center in the context of routine care from 2014 to 2019. For all premature infants and neonates with neonatal sepsis, the neonatal and maternal microbiological findings were examined to see if there was a match. Results During the study period, a total of 948 premature or newborn infants were identified as having a neonatal infection. Among all of the premature or newborn infants, 209 (22%) met the diagnostic criteria for neonatal sepsis; of these, 157 were premature births and 52 were full-term births. We evaluated the microbiological findings for these 209 mother and child pairs. No pathogens were detected in 27 out of 157 mothers of premature infants (17.1%) and in 31 out of 52 mothers of full-term infants (59.6%). In the premature infant group there were pairs with matching pathogens in 30 out of 130 cases (23.1%, 95% CI: 16.1-31.3), and in the full-term infant group there was a match in 4 out of 21 cases (19%, 95% CI: 5.4-41.9). The number needed to test to have a 90% probability of success for pathogen detection varies between 9 and 11 in the most favorable case and 26 and 32 in the least favorable case, depending on the evaluation method. Conclusion In cases of neonatal sepsis, the sepsis-causing pathogen was successfully detected through prior analysis of a maternal smear in 7% of full-term infants and in 19% of premature infants. The number needed to test was relatively high in all groups. The value of maternal smears for identifying neonatal sepsis-causing pathogens needs to be critically questioned.
CRIS-Team Scopus Importer:2023-12-08
Keywords: bacterial infection; infections; normal birth; pregnancy; premature birth

Potential of spiral breast computed tomography to increase patient comfort compared to DM - Wetzl, Matthias; Wenkel, Evelyn; Dietzel, Matthias; Siegler, Lisa; Emons, Julius; Dethlefsen, Ebba; Heindl, Felix; Kuhl, Christiane; Uder, Michael; Ohlmeyer, Sabine (European Journal of Radiology, 2021)
Purpose: To intra-individually compare patient comfort of spiral breast computed tomography (SBCT) versus digital mammography (DM).
CRIS-Team WoS Importer:2022-02-04

Practice-Changing Perspectives regarding Systemic Therapy in Early Breast Cancer: Opinions of German Experts regarding the 17th St. Gallen International Consensus Conference - Kolberg-Liedtke, Cornelia; Lueftner, Diana; Brucker, Sara Y.; Budach, Wilfried; Denkert, Carsten; Fasching, Peter; Haidinger, Renate; Harbeck, Nadia; Huober, Jens; Jackisch, Christian; Janni, Wolfgang; Krug, David; et al. (Breast Care, 2022)
The general topic of this year's 17th St. Gallen (SG) International Consensus Conference on the treatment of patients with early breast cancer (SG-BCC) was "Customizing local and systemic therapies for women with early breast cancer. " This topic considers that each treatment decision must also consider the cancer-specific situation of the individual patient. This year, the votes of the SG-BCC were again discussed taking into account the multidisciplinary German S3 Guidelines and the recommendations of the Breast Cancer Working Group of the AGO (Arbeitsgemeinschaft Gynakologische Onkologie; AGO Mamma). As the international panel of the SG-BCC consists of experts from different countries, the votes do represent an international cross-section of opinions. Therefore, it is useful to discuss the voting results with respect to the German evidence-based treatment guidelines. This publication focuses mainly on systemic treatment.
CRIS-Team WoS Importer:2022-06-17

Precancerous Lesions of the Cervix, Vulva and Vagina According to the 2014 WHO Classification of Tumors of the Female Genital Tract - Reich, O.; Regauer, S.; Marth, C.; Schmidt, D.; Horn, L. -C.; Dannecker, C.; Menton, M.; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2015)
EVALuna2:17605

Preconceptual Counseling, Prenatal Care and peripartum Management of Female Patients with Ullrich-Turner Syndrome and a High-risk cardiovascular Profile - Pontones, Constanza; Lubrich, Hannah; Schwenke, E.; Cupisti, Susanne; Dittrich, Ralf; Kehl, Sven; Beckmann, Matthias; Fahlbusch, C.; Oppelt, Patricia (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

PRECYCLE Impact of CANKADO-based eHealth-support on quality of life in metastatic breast cancer patients treated with palbociclib and endocrine therapy - Degenhardt, T.; Fasching, Peter; Lueftner, D.; Mueller, V.; Thomssen, C.; Schem, C.; Witzel, I.; Decker, T.; Tesch, H.; Kuemmel, S.; Uleer, C.; Wuerstlein, R.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

PRECYCLE: multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient-reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with palbociclib and an aromatase inhibitor or palbociclib and fulvestrant - Degenhardt, Tom; Fasching, Peter; Lüftner, Diana; Müller, Volkmar; Thomssen, Christoph; Schem, Christian; Witzel, Isabell; Decker, Thomas; Tesch, Hans; Kümmel, Sherko; Uleer, Christoph; Wuerstlein, Rachel; et al. (Trials, 2023)
Background: Efficacy and quality of life (QoL) are key criteria for therapy selection in metastatic breast cancer (MBC). In hormone receptor positive (HR +) human epidermal growth factor receptor 2 negative (HER2 −) MBC, addition of targeted oral agents such as everolimus or a cycline-dependent kinase 4/6 (CDK 4/6) inhibitor (e.g., palbociclib, ribociclib, abemaciclib) to endocrine therapy substantially prolongs progression-free survival and in the case of a CDK 4/6i also overall survival. However, the prerequisite is adherence to therapy over the entire course of treatment. However, particularly with new oral drugs, adherence presents a challenge to disease management. In this context, factors influencing adherence include maintaining patients’ satisfaction and early detection/management of side effects. New strategies for continuous support of oncological patients are needed. An eHealth-based platform can help to support therapy management and physician–patient interaction. Methods: PreCycle is a multicenter, randomized, phase IV trial in HR + HER2 − MBC. All patients (n = 960) receive the CDK 4/6 inhibitor palbociclib either in first (62.5%) or later line (37.5%) together with endocrine therapy (AI, fulvestrant) according to national guidelines. PreCycle evaluates and compares the time to deterioration (TTD) of QoL in patients supported by eHealth systems with substantially different functionality: CANKADO active vs. inform. CANKADO active is the fully functional CANKADO-based eHealth treatment support system. CANKADO inform is a CANKADO-based eHealth service with a personal login, documentation of daily drug intake, but no further functions. To evaluate QoL, the FACT-B questionnaire is completed at every visit. As little is known about relationships between behavior (e.g., adherence), genetic background, and drug efficacy, the trial includes both patient-reported outcome and biomarker screening for discovery of forecast models for adherence, symptoms, QoL, progression free survival (PFS), and overall survival (OS). Discussion: The primary objective of PreCycle is to test the hypothesis of superiority for time to deterioration (TTD) in terms of DQoL = “Deterioration of quality of life” (FACT-G scale) in patients supported by an eHealth therapy management system (CANKADO active) versus in patients merely receiving eHealth-based information (CANKADO inform). EudraCT Number: 2016–004191-22
CRIS-Team Scopus Importer:2023-06-02
Keywords: CDK 4/6 inhibitor; eHealth; Endocrine therapy; Metastatic breast cancer; Patient-reported outcome; Quality of life

PredictCBC-2.0: a contralateral breast cancer risk prediction model developed and validated in 200,000 patients - Giardiello, Daniele; Hooning, Maartje J.; Hauptmann, Michael; Keeman, Renske; Heemskerk-Gerritsen, B. A. M.; Becher, Heiko; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Camp, Nicola J.; Czene, Kamila; Devilee, Peter; et al. (Breast Cancer Research, 2022)
Background: Prediction of contralateral breast cancer (CBC) risk is challenging due to moderate performances of the known risk factors. We aimed to improve our previous risk prediction model (PredictCBC) by updated follow-up and including additional risk factors. Methods: We included data from 207,510 invasive breast cancer patients participating in 23 studies. In total, 8225 CBC events occurred over a median follow-up of 10.2 years. In addition to the previously included risk factors, PredictCBC-2.0 included CHEK2 c.1100delC, a 313 variant polygenic risk score (PRS-313), body mass index (BMI), and parity. Fine and Gray regression was used to fit the model. Calibration and a time-dependent area under the curve (AUC) at 5 and 10 years were assessed to determine the performance of the models. Decision curve analysis was performed to evaluate the net benefit of PredictCBC-2.0 and previous PredictCBC models. Results: The discrimination of PredictCBC-2.0 at 10 years was higher than PredictCBC with an AUC of 0.65 (95% prediction intervals (PI) 0.56–0.74) versus 0.63 (95%PI 0.54–0.71). PredictCBC-2.0 was well calibrated with an observed/expected ratio at 10 years of 0.92 (95%PI 0.34–2.54). Decision curve analysis for contralateral preventive mastectomy (CPM) showed the potential clinical utility of PredictCBC-2.0 between thresholds of 4 and 12% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. Conclusions: Additional genetic information beyond BRCA1/2 germline mutations improved CBC risk prediction and might help tailor clinical decision-making toward CPM or alternative preventive strategies. Identifying patients who benefit from CPM, especially in the general breast cancer population, remains challenging.
CRIS-Team Scopus Importer:2022-11-04
Keywords: BCAC; BRCA1/2 germline mutation; Breast Cancer Association Consortium; Breast cancer genetic predisposition; Clinical decision-making; Contralateral breast cancer; Contralateral preventive mastectomy; Polygenic risk score; Prediction performance; Risk prediction

Predicting attention deficit hyperactivity disorder using pregnancy and birth characteristics - Schwenke, Eva; Fasching, Peter; Faschingbauer, Florian; Pretscher, Jutta; Kehl, Sven; Peretz, Roberta; Keller, Andrea; Häberle, Lothar; Eichler, Anna; Irlbauer-Müller, Viktoria; Dammer, Ulf; Beckmann, Matthias; et al. (Archives of Gynecology and Obstetrics, 2018)
PURPOSE: The aim of this study was to evaluate maternal, prenatal, perinatal, and postpartum parameters as risk factors for the later development of an attention deficit hyperactivity disorder (ADHD) in the child. METHODS: Women who had given birth at Erlangen University Hospital between 1996 and 1999 were sent a questionnaire in 2009. The results of the questionnaire were correlated with the prospectively collected data for the births in 1996-1999. RESULTS: A total of 573 mother and child pairs were analyzed. Forty-four of the mothers reported that their child had ADHD (7.7%). No significant associations were found for the following parameters: mother's age; mother's educational level; number of the pregnancy; maternal weight before and at the end of pregnancy; mother's height; alcohol consumption during pregnancy; mode of delivery; gestational week; birthweight; umbilical artery blood values; Apgar score at 5 and 10 min; or breastfeeding. The parameters of smoking in pregnancy and an Apgar score lower than 7 after 1 min were significantly associated with a risk for later development of ADHD. CONCLUSIONS: This analysis of maternal, prenatal, perinatal, and postnatal parameters found that smoking in pregnancy and a low Apgar score 1 min after birth are associated with a significantly greater risk for the development of ADHD. Beyond the question of the causal mechanism involved, this is a relevant finding, since smoking during pregnancy is a preventable risk factor.
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Predicting mammographic density with linear ultrasound transducers - Behrens, Annika; Fasching, Peter; Schwenke, Eva; Gaß, Paul; Häberle, Lothar; Heindl, Felix; Heusinger, Katharina; Lotz, Laura; Lubrich, Hannah; Preuß, Caroline; Schneider, Michael; Schulz-Wendtland, Rüdiger; et al. (European Journal of Medical Research, 2023)
Background: High mammographic density (MD) is a risk factor for the development of breast cancer (BC). Changes in MD are influenced by multiple factors such as age, BMI, number of full-term pregnancies and lactating periods. To learn more about MD, it is important to establish non-radiation-based, alternative examination methods to mammography such as ultrasound assessments. Methods: We analyzed data from 168 patients who underwent standard-of-care mammography and performed additional ultrasound assessment of the breast using a high-frequency (12 MHz) linear probe of the VOLUSON® 730 Expert system (GE Medical Systems Kretztechnik GmbH & Co OHG, Austria). Gray level bins were calculated from ultrasound images to characterize mammographic density. Percentage mammographic density (PMD) was predicted by gray level bins using various regression models. Results: Gray level bins and PMD correlated to a certain extent. Spearman’s ρ ranged from − 0.18 to 0.32. The random forest model turned out to be the most accurate prediction model (cross-validated R 2, 0.255). Overall, ultrasound images from the VOLUSON® 730 Expert device in this study showed limited predictive power for PMD when correlated with the corresponding mammograms. Conclusions: In our present work, no reliable prediction of PMD using ultrasound imaging could be observed. As previous studies showed a reasonable correlation, predictive power seems to be highly dependent on the device used. Identifying feasible non-radiation imaging methods of the breast and their predictive power remains an important topic and warrants further evaluation. Trial registration 325-19 B (Ethics Committee of the medical faculty at Friedrich Alexander University of Erlangen-Nuremberg, Erlangen, Germany).
CRIS-Team Scopus Importer:2023-10-13
Keywords: Breast cancer risk; Percent mammographic density; Ultrasound

Predicting prognosis of breast cancer patients with brain metastases in the BMBC registry: Comparison of three different - Riecke, K.; Mueller, V.; Neunhoeffer, T.; Weide, R.; Schmidt, M.; Park-Simon, T. -W.; Mundhenke, Christoph; Polasik, A.; Hesse, T.; Luebbe, K.; Laakmann, E.; Thill, M.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-06-26

Predicting prognosis of breast cancer patients with brain metastases in the BMBC registry—comparison of three different GPA prognostic scores - Riecke, Kerstin; Müller, Volkmar; Weide, Rudolf; Schmidt, Marcus; Park‐simon, Tjoung Won; Möbus, Volker; Mundhenke, Christoph; Polasik, Arkadius; Lübbe, Kristina; Hesse, Tobias; Laakmann, Elena; Thill, Marc; et al. (Cancers, 2021)
Several scores have been developed in order to estimate the prognosis of patients with brain metastases (BM) by objective criteria. The aim of this analysis was to validate all three published graded‐prognostic‐assessment (GPA)‐scores in a subcohort of 882 breast cancer (BC) patients with BM in the Brain Metastases in the German Breast Cancer (BMBC) registry. The median age at diagnosis of BM was 57 years. All in all, 22.3% of patients (n = 197) had triple‐negative, 33.4% (n = 295) luminal A like, 25.1% (n = 221) luminal B/HER2‐enriched like and 19.2% (n = 169) HER2 positive like BC. Age ≥60 years, evidence of extracranial metastases (ECM), higher number of BM, triple‐negative subtype and low Karnofsky‐Performance‐Status (KPS) were all associated with worse overall survival (OS) in univariate analysis (p < 0.001 each). All three GPA‐scores were associated with OS. The breast‐GPA showed the highest probability of classifying patients with survival above 12 months in the best prognostic group (specificity 68.7% compared with 48.1% for the updated breast‐GPA and 21.8% for the original GPA). Sensitivities for predicting 3 months survival were very low for all scores. In this analysis, all GPA‐scores showed only moderate diagnostic accuracy in predicting the OS of BC patients with BM.
CRIS-Team Scopus Importer:2021-03-05
Keywords: Brain metastases; Breast cancer; Prognostic scores

Predicting prognosis of breast cancer patients with brain metastases in the BMBC registry - comparison of three different prognostic scores - Riecke, K.; Mueller,; Neunhoeffer, T.; Weide, R.; Schmidt, M.; Park-Simon, T. W.; Mundhenke, Christoph; Polasik, A.; Hesse, T.; Luebbe, K.; Laakmann, E.; Thill, M.; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Predicting Triple-Negative Breast Cancer Subtype Using Multiple Single Nucleotide Polymorphisms for Breast Cancer Risk and Several Variable Selection Methods - Häberle, Lothar; Hein, Alexander; Rübner, Matthias; Schneider, Michael; Ekici, Arif Bülent; Gaß, Paul; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Beckmann, Matthias; Lo, Wing-Yee; Schroth, Werner; Brauch, Hiltrud; et al. (Geburtshilfe und Frauenheilkunde, 2017)
Studies of triple-negative breast cancer have recently been extending the inclusion criteria and incorporating additional molecular markers into the selection criteria, opening up scope for targeted therapies. The screening phases required for studies of this type are often prolonged, since the process of determining the molecular subtype and carrying out additional biomarker assessment is time-consuming. Parameters such as germline genotypes capable of predicting the molecular subtype before it becomes available from pathology might be helpful for treatment planning and optimizing the timing and cost of screening phases. This appears to be feasible, as rapid and low-cost genotyping methods are becoming increasingly available. The aim of this study was to identify single nucleotide polymorphisms (SNPs) for breast cancer risk capable of predicting triple negativity, in addition to clinical predictors, in breast cancer patients.This cross-sectional observational study included 1271 women with invasive breast cancer who were treated at a university hospital. A total of 76 validated breast cancer risk SNPs were successfully genotyped. Univariate associations between each SNP and triple negativity were explored using logistic regression analyses. Several variable selection and regression techniques were applied to identify a set of SNPs that together improve the prediction of triple negativity in addition to the clinical predictors of age at diagnosis and body mass index (BMI). The most accurate prediction method was determined by cross-validation.The SNP rs10069690 (TERT, CLPTM1L) was the only significant SNP (corrected p = 0.02) after correction of p values for multiple testing in the univariate analyses. This SNP and three additional SNPs from the genes RAD51B, CCND1, and FGFR2 were selected for prediction of triple negativity. The addition of these SNPs to clinical predictors increased the cross-validated area under the curve (AUC) from 0.618 to 0.625. Age at diagnosis was the strongest predictor, stronger than any genetic characteristics.Prediction of triple-negative breast cancer can be improved if SNPs associated with breast cancer risk are added to a prediction rule based on age at diagnosis and BMI. This finding could be used for prescreening purposes in complex molecular therapy studies for triple-negative breast cancer.
EVALuna2:6850

Prediction and clinical utility of a contralateral breast cancer risk model - Giardiello, Daniele; Steyerberg, Ewout W.; Hauptmann, Michael; Adank, Muriel A.; Akdeniz, Delal; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Brinkhuis, Mariël; Chang-Claude, Jenny; Czene, Kamila; Devilee, Peter; et al. (Breast Cancer Research, 2019)
BACKGROUND: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS: In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS: We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.
CRIS-Team Scopus Importer:2019-12-31
Keywords: BRCA mutation carriers; Clinical decision-making; Contralateral breast cancer; Risk prediction model

Prediction of breast cancer risk based on profiling with common genetic variants - Mavaddat, Nasim; Pharoah, Paul D. P.; Michailidou, Kyriaki; Tyrer, Jonathan; Brook, Mark N.; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; et al. (Journal of the National Cancer Institute, 2015)
Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this repor
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Prediction of contralateral breast cancer: external validation of risk calculators in 20 international cohorts - Giardiello, Daniele; Hauptmann, Michael; Steyerberg, Ewout W.; Adank, Muriel A.; Akdeniz, Delal; Blom, Jannet C.; Blomqvist, Carl; Bojesen, Stig E.; Bolla, Manjeet K.; Brinkhuis, Mariel; Chang-Claude, Jenny; Czene, Kamila; et al. (Breast Cancer Research and Treatment, 2020)
Background Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). Methods We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. Results The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. Conclusions Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.
CRIS-Team WoS Importer:2020-04-24

Prediction of pathological complete response and prognosis in patients with neoadjuvant treatment for triple-negative breast cancer - Gaß, Paul; Lux, Michael P.; Rauh, Claudia; Hein, Alexander; Bani, Mayada; Fießler, Cornelia; Hartmann, Arndt; Häberle, Lothar; Pretscher, Jutta; Erber, Ramona; Wachter, David; Schulz-Wendtland, Rüdiger; et al. (BMC Cancer, 2018)
BACKGROUND: It has been reported that pathological complete response is an important surrogate marker for disease-free survival and overall survival in patients with triple-negative breast cancer. This study investigates predictors of the response to neoadjuvant platinum-based or anthracycline-based treatment, and of the prognosis, in patients with triple-negative breast cancer. METHODS: A total of 121 patients with triple-negative breast cancer received neoadjuvant treatment with either platinum or anthracycline between 2008 and 2013. Pathological complete response was assessed relative to different treatments using logistic regression models with age, clinical tumor stage, grading, and Ki-67 as predictors and interaction terms, to obtain adjusted and subgroup-specific results. The impact of the pathological complete response rate on disease-free survival and overall survival was also analyzed. RESULTS: The pathological complete response rate was higher after platinum/taxane treatment compared with anthracycline/taxane (50.0% vs. 41.8%), but this was not significant in the adjusted analysis (OR 1.44; 95% CI, 0.68 to 3.09). A high histological grade (G3) was a predictor for higher pathological complete response in platinum-based therapy (OR 2.27; 95% CI, 1.00 to 5.30). The effect of neoadjuvant chemotherapy on pathological complete response was significantly different for G1-2 vs. G3 (Pinteraction = 0.013), and additional subgroup-specific differences were noted. Pathological complete response was a predictor for improved disease-free survival and overall survival in both treatment groups, with and without platinum chemotherapy. CONCLUSIONS: This retrospective study of patients with triple-negative breast cancer adds to the evidence that the treatment effect of platinum may be greatest particularly in G3 tumors. In addition, the effect of pathological complete response on the prognosis does not depend on the treatment used.
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Preexisting musculoskeletal burden and its development under letrozole treatment in early breast cancer patients - Nabieva, Naiba; Häberle, Lothar; Brucker, Sara Y.; Janni, Wolfgang; Volz, Bernhard; Löhberg, Christian; Hartkopf, Andreas D.; Walter, Christina Barbara; Baake, Gerold; Fridman, Alexander; Malter, Wolfram; Wuerstlein, Rachel; et al. (International Journal of Cancer, 2019)
One of the most common adverse events (AEs) occurring during treatment with aromatase inhibitors (AIs) is musculoskeletal pain. The aim of our study was to analyze the influence of preexisting muscle/limb pain and joint pain on the development of AI-induced musculoskeletal AEs. Women eligible for upfront adjuvant endocrine therapy with letrozole were included in the PreFace study, a multicenter phase IV trial. During the first treatment year, they were asked to record musculoskeletal AEs monthly by answering questions regarding pain symptoms and rating the pain intensity on a numeric rating scale from 0 (no pain) to 10 (very strong pain). Pain values were compared using nonparametric statistical tests. Overall, 1,416 patients were evaluable. The average pain value over all time points in women with preexisting muscle/limb pain was 4.3 (median 4.3); in those without preexisting pain, it was 2.0 (median 1.7). In patients without preexisting muscle/limb pain, pain levels increased relatively strongly within the first 6 months (mean increase +0.9, p < 0.00001) in comparison with those with preexisting pain (mean increase +0.3, p < 0.001), resulting in a statistically significant difference (p < 0.00001) between the two groups. The development of joint pain was similar in the two groups. Women without preexisting muscle/limb pain or joint pain have the greatest increase in pain after the start of adjuvant AI therapy. Women with preexisting pain have significantly higher pain values. The main increase in pain values takes place during the first 6 months of treatment.
Keywords: aromatase inhibitor; arthralgia/joint pain; breast cancer; endocrine treatment/therapy; letrozole; myalgia/muscle and limb pain

Pregnancies and live births after 20 transplantations of cryopreserved ovarian tissue in a single center - Dittrich, Ralf; Hackl, Janina; Lotz, Laura; Hoffmann, Inge; Beckmann, Matthias (Fertility and Sterility, 2015)
To report the results of 20 orthotopic retransplantations of cryopreserved ovarian tissue after cancer treatment.Retrospective analysis.Tertiary gynecology department.Twenty patients with malignant disease: 11 with hematological malignancies (55%), four with breast cancer (20%), three with anal cancer (15%), and two with ovarian cancer (10%); the mean age before oncological treatment was 30.5 years.Ovarian tissue was removed from patients in various centers in Germany in 2005-2009. All patients received chemotherapy and/or radiotherapy. Afterward, 17 patients had complete premature ovarian insufficiency, while three still showed some ovarian activity. Overnight transportation of tissue before freezing was necessary in eight cases. Cryopreservation followed slow freezing protocols in all cases. Retransplantation was performed at Erlangen University Hospital 3.75 years after extraction, on average. Thawed tissue was transplanted into a peritoneal pouch in the broad ligament region, below the tube, in 16 cases. Fragments were sutured both onto the remaining ovary and into a peritoneal pouch in four cases.Restoration of ovarian activity, pregnancy, birth.Ovarian activity resumed in all patients except one. Seven patients conceived, with one miscarriage and four ongoing pregnancies. Four patients delivered healthy babies. One pregnancy and live birth after oocyte donation need to be considered separately.These data clearly demonstrate that preserving fertility by cryopreserving ovarian tissue is a successful and safe clinical option that can be considered for selected cancer patients.
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Pregnancy and Obstetrical Outcomes in Women Over 40 Years of Age - Dietl, A.; Cupisti, S.; Beckmann, Matthias; Schwab, M.; Zollner, U. (Geburtshilfe und Frauenheilkunde, 2015)
Introduction: Delayed childbearing is increasing, and advanced maternal age has been associated with an increased risk of obstetrical complications. The purpose of this study was to evaluate pregnancy outcomes in women with advanced maternal age (>= 40 years). Methods: Maternal and obstetrical data were collected from the Department of Obstetrics and Gynecology of the University of Wuerzburg for the period from 2006 to 2011. In this retrospective analysis we compared the outcomes for women aged >= 40 years (n = 405) with those of three younger subgroups (I: < 30 y; II: 30-34 y; III: 35-39 y). Results: Pregnant women older than 40 years had more chronic diseases such as hypertension, needed medical treatment more frequently and had a higher thrombosis risk. Pregnancy-induced diseases such as gestational diabetes, preeclampsia and pregnancy-associated hypertension occurred more often in women >= 40 years of age. Compared to mothers who were younger than 30 years, primiparous women >= 40 years had a more than four times higher overall cesarean section rate and four times higher elective cesarean section rate. Furthermore, they required longer hospital stays, both after cesarean section and after vaginal delivery. The preterm birth rate (<= 32 weeks of gestation) was similar across the different age groups. Conclusions: The outcomes of pregnancy and childbirth and for newborns born to women >= 40 years did not vary significantly from those of younger women if the following conditions were met: a) pre-existing chronic diseases were treated medically and dietetically; b) pregnancy-induced morbidity was monitored regularly and controlled medically; c) women attended regular prenatal check-ups; d) a healthy lifestyle was adhered to during pregnancy, and e) delivery occurred in a perinatal center.
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Preliminary observations on whole-ovary xenotransplantation as an experimental model for fertility preservation - Nichols-Burns, Stephanie M.; Lotz, Laura; Schneider, Heike; Adamek, Edyta; Daniel, Christoph; Stief, Andrea; Grigo, Christina; Klump, Dorothee; Hoffmann, Inge; Beckmann, Matthias; Dittrich, Ralf (Reproductive Biomedicine Online, 2014)
Ovarian tissue preservation and retransplantation is a promising strategy to restore fertility in cancer survivors. Ischaemia accompanying ovarian tissue grafting, however, can lead to significant follicle loss. Transplantation of the whole ovary by vascular anastomosis has been considered as an alternative to prevent widespread ischaemic damage. In this study, the feasibility and function of transplanting whole ovary with intact vasculature were evaluated, with the goal of developing a xenograft model for studies using donated human ovaries. Whole-swine ovaries with vascular pedicles were perfused and transplanted as intact ovaries by anastomosis into irradiated ovariectomized nude rats (n = 10). The observation period was between 1 and 4 weeks. Fresh swine ovaries served as controls (n = 10). Ovarian stroma and follicle populations were assessed through histological examination in both transplanted and control ovaries. Most of the transplanted whole ovaries (n = 6) maintained stromal quality and all preantral follicle classes were represented, although follicle numbers decreased compared with fresh control. Four transplanted ovaries were fibrotic after 1-4 weeks within the nude rat. Our results demonstrate transplantation of whole-pig ovary into nude rats is possible and support development of this xenograft model system for human studies.
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Prenatal alcohol exposure and the facial phenotype in adolescents: A study based on meconium ethyl glucuronide - Maschke, Janina; Roetner, Jakob; Goecke, Tamme; Fasching, Peter; Beckmann, Matthias; Kratz, Oliver; Moll, Gunther; Lenz, Bernd; Kornhuber, Johannes; Eichler, Anna (Brain Sciences, 2021)
Here, we explore the effects of prenatal alcohol exposure (PAE) in adolescence. We investigated associations between meconium ethyl glucoronide (EtG) and facial malformation. For 29 children (66/63 male/female; M = 13.3, SD = 0.32, 12–14 years), PAE was implemented by newborn meconium EtG and maternal self-reports during the third trimester. Cognitive development was operationalized by standardized scores (WISC V). The EtG cut-off values were set at ≥10 ng/g (n = 32, 24.8% EtG10+) and ≥112 ng/g (n = 20, 15.5% EtG112+). The craniofacial shape was measured using FAS Facial Photographic Analysis Software. EtG10+− and EtG112+-affected children exhibited a shorter palpebral fissure length (p = 0.031/p = 0.055). Lip circularity was smaller in EtG112+-affected children (p = 0.026). Maternal self-reports were not associated (p > 0.164). Lip circularity correlated with fluid reasoning (EtG10+ p = 0.031; EtG112+ p = 0.298) and working memory (EtG10+ p = 0.084; EtG112+ p = 0.144). The present study demonstrates visible effects of the facial phenotype in exposed adolescents. Facial malformation was associated with a child’s cognitive performance in the alcohol-exposed group. The EtG biomarker was a better predictor than maternal self-reports.
CRIS-Team Scopus Importer:2021-03-19
Keywords: Alcohol; Biomarker; Craniofacial shape; Ethyl glucuronide (EtG); Facial malformations; Inner canthal distance; Intrauterine alcohol exposure; Lip circularity; Meconium; Palpebral fissure length

Prenatal Alcohol Exposure Is Associated With Adverse Cognitive Effects and Distinct Whole-Genome DNA Methylation Patterns in Primary School Children - Frey, Silke; Eichler, Anna; Stonawski, Valeska; Kriebel, Jennifer; Wahl, Simone; Gallati, Sabina; Goecke, Tamme W.; Fasching, Peter A.; Beckmann, Matthias W.; Kratz, Oliver; Moll, Gunther; Heinrich, Hartmut; et al. (Frontiers in Behavioral Neuroscience, 2018)
Prenatal alcohol exposure (PAE) is known to elicit a broad range of systemic effects, including neurophysiological alterations that result in adverse behavioral and cognitive outcomes. However, molecular pathways underlying these long-term intrauterine effects remain to be investigated. Here, we tested a hypothesis that PAE may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. We report the results of the study that included 156 primary school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. Thirty-two newborns were found to be exposed to alcohol with EtG values above 30 ng/g (EtG+). Previously we described PAE being associated with lower IQ and smaller amplitude of the event-related potential component P3 in go trials (Go-P3), which indicates a reduced capacity of attentional resources. Whole-genome methylation analysis of the buccal cell DNA revealed 193 differentially methylated genes in children with positive meconium EtG, that were clustered into groups involved in epigenetic modifications, neurodegeneration, neurodevelopment, axon guidance and neuronal excitability. Furthermore, we detected mediation effects of the methylation changes in DPP10 and SLC16A9 genes on the EtG related cognitive and attention-related deficits. Our results suggest that system-wide epigenetic changes are involved in long-term effects of PAE. In particular, we show an epigenetic mediation of PAE effects on cognition and attention-related processes.
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Prenatal and adult androgen activities in alcohol dependence - Lenz, Bernd; Mühle, Christiane; Braun, B.; Weinland, C.; Bouna-Pyrrou, Polyxeni; Behrens, Juliane; Kubis, S.; Mikolaiczik, Katrin; Muschler, M. -R.; Saigali, Sarah; Sibach, M.; Tanovska, P.; et al. (Acta Psychiatrica Scandinavica, 2017)
OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.
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Prenatal Androgen Influence on Addictive Behaviour in Adolescence Vorgeburtlicher Androgen- einfluss auf süchtiges Verhalten in der Adoleszenz - Lenz, Bernd; Eichler, Anna; Buchholz, Verena Nadine; Fasching, Peter; Kornhuber, Johannes (Sucht, 2021)
Background: Men consume alcohol, tobacco, and illicit drugs more often than women, and they are more prone to pathological gambling and addictive internet gaming. These sex differences are already found during adolescence. The consumption patterns are related to externalizing behavior. In addition to social influences, biological factors play a central role in the development of these differences between men and women. Prenatal exposure to androgens and estrogens shape the brain development with functional and structural effects that persist into adulthood. Intrauterine sex hormone exposure is related to maternal risk factors such as stress and substance use. Aim: In this narrative review, we discuss the potential impact of prenatal androgen exposure in the womb on the development of addictive behaviors and self-regulation in later life. In recent years, this issue has been addressed by animal experiments with direct modulation of prenatal androgenization and clinical association studies based on biomarkers such as the second-to-fourth finger lengths ratio (2D:4D). Results: The available body of literature suggests that reinforced brain androgenization during the intrauterine development increases the risk for addictive behaviors and deficits in self-regulation capacity in later life. Finally, we also discuss prevention strategies during pregnancy targeting this model and refer to the Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention study. This investigation is a subproject of the IMAC-Mind research collaborative project to improve mental health and reduce addiction risk in childhood and adolescence through mindfulness.
CRIS-Team Scopus Importer:2021-12-24
Keywords: addiction; adolescence; dependence; prenatal development; testosterone

Prenatal Correction of X-Linked Hypohidrotic Ectodermal Dysplasia - Schneider, Holm; Faschingbauer, Florian; Schuepbach-Mallepell, Sonia; Koerber, Iris; Wohlfart, Sigrun; Dick, Angela; Wahlbuhl, Mandy; Kowalczyk-Quintas, Christine; Vigolo, Michele; Kirby, Neil; Tannert, Corinna; Rompel, Oliver; et al. (New England Journal of Medicine, 2018)
Genetic deficiency of ectodysplasin A (EDA) causes X-linked hypohidrotic ectodermal dysplasia (XLHED), in which the development of sweat glands is irreversibly impaired, an condition that can lead to life-threatening hyperthermia. We observed normal development of mouse fetuses with Eda mutations after they had been exposed in utero to a recombinant protein that includes the receptor-binding domain of EDA. We administered this protein intraamniotically to two affected human twins at gestational weeks 26 and 31 and to a single affected human fetus at gestational week 26; the infants, born in week 33 (twins) and week 39 (singleton), were able to sweat normally, and XLHED-related illness had not developed by 14 to 22 months of age. (Funded by Edimer Pharmaceuticals and others.).
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Presence of circulating tumor cells in high-risk early breast cancer during follow-up and prognosis - Trapp, Elisabeth; Janni, Wolfgang; Schindlbeck, Christian; Jückstock, Julia; Andergassen, Ulrich; De Gregorio, Amelie; Alunni-Fabbroni, Marianna; Tzschaschel, Marie; Polasik, Arkadius; Koch, Julian G.; Friedl, Thomas W.P.; Fasching, Peter; et al. (Journal of the National Cancer Institute, 2019)
Background: The prognostic relevance of circulating tumor cells (CTCs) at the time of primary diagnosis has been well established. However, little information is available regarding their prognostic relevance to follow-up care. Methods: The multicenter, open-label, phase III SUCCESS A trial compared two adjuvant chemotherapy regimens followed by 2 vs 5 years of zoledronate for early-stage, high-risk breast cancer patients. The presence of CTCs was assessed before and 2 years after chemotherapy using the FDA-approved CellSearch System. Overall survival (OS) and disease-free survival (DFS) were analyzed using univariate log-rank tests and multivariable Cox regressions. OS and DFS were measured starting from an assessment of CTCs 2 years after the completion of chemotherapy. All statistical tests were two-sided. Results: The sample included 1087 patients who participated in the translational research program of the SUCCESS A trial and for whom sufficient translational data were available regarding CTC status at baseline and at the 2-year follow-up visit. Two years after chemotherapy, 198 (18.2%) patients were CTC-positive. The median follow-up after this timepoint was 37 months. Cox regressions that included CTC status at baseline revealed that CTC status 2 years after chemotherapy had statistically significant and independent prognostic relevance for OS (hazard ratio [HR] ¼ 3.91, 95% confidence interval [CI] ¼ 2.04 to 7.52, P < .001) and DFS (HR ¼ 2.31, 95% CI ¼ 1.50 to 3.55, P < .001). Conclusion: The presence of CTCs 2 years after chemotherapy was associated with decreased OS and DFS. Based on these results, active individualized surveillance strategies for breast cancer survivors based on biomarkers should be reconsidered.
CRIS-Team Scopus Importer:2019-09-24

Prevalence and course of pregnancy symptoms using self-reported pregnancy app symptom tracker data - Nissen, Michael; Barrios Campo, Nuria; Flaucher, Madeleine; Jäger, Katharina; Titzmann, Adriana; Blunck, Dominik; Fasching, Peter; Engelhardt, Victoria; Eskofier, Björn; Leutheuser, Heike (npj Digital Medicine, 2023)
During pregnancy, almost all women experience pregnancy-related symptoms. The relationship between symptoms and their association with pregnancy outcomes is not well understood. Many pregnancy apps allow pregnant women to track their symptoms. To date, the resulting data are primarily used from a commercial rather than a scientific perspective. In this work, we aim to examine symptom occurrence, course, and their correlation throughout pregnancy. Self-reported app data of a pregnancy symptom tracker is used. In this context, we present methods to handle noisy real-world app data from commercial applications to understand the trajectory of user and patient-reported data. We report real-world evidence from patient-reported outcomes that exceeds previous works: 1,549,186 tracked symptoms from 183,732 users of a smartphone pregnancy app symptom tracker are analyzed. The majority of users track symptoms on a single day. These data are generalizable to those users who use the tracker for at least 5 months. Week-by-week symptom report data are presented for each symptom. There are few or conflicting reports in the literature on the course of diarrhea, fatigue, headache, heartburn, and sleep problems. A peak in fatigue in the first trimester, a peak in headache reports around gestation week 15, and a steady increase in the reports of sleeping difficulty throughout pregnancy are found. Our work highlights the potential of secondary use of industry data. It reveals and clarifies several previously unknown or disputed symptom trajectories and relationships. Collaboration between academia and industry can help generate new scientific knowledge.
CRIS-Team Scopus Importer:2023-10-20

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer - Schramm, Amelie; Schochter, Fabienne; Friedl, Thomas W. P.; De Greqorio, Nikolaus; Andergassen, Ulrich; Alunni-Fabbroni, Marianna; Trapp, Elisabeth; Jaeger, Bernadette; Heinrich, Georg; Camara, Oumar; Decker, Thomas; Ober, Angelika; et al. (Clinical Breast Cancer, 2017)
BACKGROUND: Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. METHODS: The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). RESULTS: Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). CONCLUSIONS: The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary findings.
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Prevalence of circulating tumor cells in early breast cancer patients 2 and 5 years after adjuvant treatment - Bauer, Emanuel C. A.; Schochter, Fabienne; Widschwendter, Peter; Degregorio, Amelie; Andergassen, Ulrich; Friedl, Thomas W. P.; Fasching, Peter; Fehm, Tanja; Schneeweiss, Andreas; Beckmann, Matthias; Pantel, Klaus; Janni, Wolfgang; et al. (Breast Cancer Research and Treatment, 2018)
Several studies have provided evidence on the prognostic relevance of circulating tumor cells (CTCs) detected before and after chemotherapy regarding overall survival (OS) and progression-free survival (PFS) in early breast cancer (EBC). We provide data on the prevalence of CTCs 2 and 5 years after primary diagnosis in a cohort of patients with EBC.The SUCCESS study is a multicenter, prospective, randomized trial comparing PFS in primary breast cancer patients undergoing one of two adjuvant chemotherapy regimens followed by 2 versus 5 years of treatment with zoledronate. CTCs from patients without signs of breast cancer recurrence were analyzed in peripheral blood using the FDA cleared CellSearch® System (Veridex, USA) 2 and 5 years after primary diagnosis.CTCs were detected at 2 and 5 years after primary diagnosis in 96 (16.7%) and 47 (8.2%) of the 574 patients, respectively. There were no associations between CTC status and patient and tumor characteristics or treatment regimens. In 442 (77.0%) patients, no CTCs were detected at either of the two time points, and in 11 patients (1.9%), CTCs were found at both 2 and 5 years after primary diagnosis. In 85 (14.8%) patients, CTCs were present 2 years after primary diagnosis but not after 5 years, while 36 (6.3%) patients had CTCs in their blood only at the 5-year follow-up.In patients with EBC, CTCs can be detected even 5 years after primary diagnosis without clinical signs of disease recurrence.
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Prevalence of SARS-CoV-2 in Pregnant Women Assessed by RT-PCR in Franconia, Germany: First Results of the SCENARIO Study (SARS-CoV-2 prEvalence in pregNAncy and at biRth In FrancOnia) - Hein, Alexander; Kehl, Sven; Häberle, Lothar; Tiemann, Carsten; Peuker, Rebecca; Mereutanu, Denise; Stumpfe, Florian; Faschingbauer, Florian; Meyer-Schlinkmann, Kirstin; Koch, Martin C.; Kainer, Franz; Dammer, Ulf; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Purpose Detection of SARS-CoV-2-infected pregnant women admitted to maternity units during a pandemic is crucial. In addition to the fact that pregnancy is a risk factor for severe COVID-19 and that medical surveillance has to be adjusted in infected women and their offspring, knowledge about infection status can provide the opportunity to protect other patients and healthcare workers against virus transmission. The aim of this prospective observational study was to determine the prevalence of SARS-CoV-2 infection among pregnant women in the hospital setting. Material and Methods All eligible pregnant women admitted to the nine participating hospitals in Franconia, Germany, from 2 June 2020 to 24 January 2021 were included. COVID-19-related symptoms, secondary diseases and pregnancy abnormalities were documented. SARS-CoV-2 RNA was detected by RT-PCR from nasopharyngeal swabs. The prevalence of acute SARS-CoV-2 infection was estimated by correcting the positive rate using the Rogan-Gladen method. The risk of infection for healthcare workers during delivery was estimated using a risk calculator. Results Of 2414 recruited pregnant women, six were newly diagnosed RT-PCR positive for SARS-CoV-2, which yielded a prevalence of SARS-CoV-2 infection of 0.26% (95% CI, 0.10-0.57%). Combining active room ventilation and wearing FFP2 masks showed an estimated reduction of risk of infection for healthcare workers in the delivery room to < 1%. Conclusions The prevalence of newly diagnosed SARS-CoV-2 infection during pregnancy in this study is low. Nevertheless, a systematic screening in maternity units during pandemic situations is important to adjust hygienic and medical management. An adequate hygienic setting can minimise the calculated infection risk for medical healthcare workers during patients' labour.
CRIS-Team Scopus Importer:2022-02-25
Keywords: COVID-19; infection; pregnancy; prevalence; SARS-CoV-2

Prevention of Cervical Cancer - Hillemanns, Peter; Friese, Klaus; Dannecker, Christian; Klug, Stefanie; Seifert, Ulrike; Iftner, Thomas; Haedicke, Juliane; Loening, Thomas; Horn, Lars; Schmidt, Dietmar; Ikenberg, Hans; Steiner, Manfred; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.
CRIS-Team Scopus Importer:2019-05-02
Keywords: cervical cancer; cervical intraepithelial neoplasia (CIN); cervical precancerous condition; HPV

Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 1 with Introduction, Screening and the Pathology of Cervical Dysplasia - Hillemanns, Peter; Friese, Klaus; Dannecker, Christian; Klug, Stefanie; Seifert, Ulrike; Iftner, Thomas; Haedicke, Juliane; Loening, Thomas; Horn, Lars; Schmidt, Dietmar; Ikenberg, Hans; Steiner, Manfred; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Annual opportunistic screening for cervical carcinoma has been carried out in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as the guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. The first part of this short summary presents the pathological basis and considers various questions related to screening for cervical cancer. As also reported in earlier reviews, the meta-analysis by Kleijnen Systematic Reviews showed that HPV-based screening offers better protection against invasive cervical cancer compared to cytology-based screening. The authors of this guideline therefore recommend - in accordance with the guideline of the Joint National Committee of Germany (Gemeinsamer Bundesauschuss, G-BA) - that women aged 35 and above should be examined at regular intervals (at least every 3 years) and undergo HPV-based screening. Co-testing can also be carried out. Women between the ages of 20 and 35 should have cytological screening every 2 years.
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Primäre Prävention - Mamma- und Genitalkarzinome - Preu, Caroline; Heindl, Felix; Hein, Alexander; Koch, Martin; Ga, Paul; Beckmann, Matthias; Lux, Michael P.; Emons, Julius (TumorDiagnostik & Therapie, 2019)
Zusammenfassung In den letzten Jahren haben sich Diagnostik und Therapie im Bereich der gynäkologischen Onkologie und Senologie stetig weiterentwickelt. Dennoch ist das Versterben an einer Krebserkrankung in den hoch entwickelten Ländern eine der häufigsten Todesursachen der Frau 1. Manahmen zur Primärprävention sind daher von hoher Bedeutung, um die Morbidität und Mortalität von Krebserkrankungen zu senken.
CRIS-Team Scopus Importer:2019-08-13
Keywords: Endometriumkarzinom; Mammakarzinom; Ovarialkarzinom; primäre Prävention; Zervixkarzinom

Primary Therapy of Early Breast Cancer: Evidence, Controversies, Consensus - Untch, Michael; Thomssen, Christoph; Bauerfeind, Ingo; Braun, Michael; Brucker, Sara Y.; Felberbaum, Ricardo; Hagemann, Friederike; Haidinger, Renate; Hönig, Arnd; Huober, Jens; Jackisch, Christian; Kolberg, Hans Christian; et al. (Geburtshilfe und Frauenheilkunde, 2019)
The results of the international St. Gallen Consensus Conference for the treatment of patients with primary breast cancer were discussed this year by a working group of leading breast cancer experts in view of the therapy recommendations for everyday clinical practice in Germany. Three of the breast cancer experts are also members of this year's St. Gallen panel. The comparison of the St. Gallen recommendations with the annually updated treatment recommendations of the AGO 2019 as well as the S3 guideline is useful, since the recommendations of the St. Gallen panel represent the opinions of experts from various countries and disciplines. The recommendations of the S3 guideline and AGO are based on evidence-based research of the literature. This year's 16th St. Gallen conference featured the motto Magnitude of clinical benefit. In addition to the evidence-based data, each therapeutic decision must also undergo a benefit/risk assessment of the patient's individual situation and be discussed with the patient.
CRIS-Team Scopus Importer:2019-06-28
Keywords: axilla; early breast cancer; locoregional therapy; neoadjuvant treatment; St. Gallen consensus 2019; systemic therapy

Primary Therapy of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: Opinions of German Specialists to the 14th St. Gallen International Breast Cancer Conference 2015 (Vienna 2015) - Untch, M.; Harbeck, N.; Huober, J.; Von Minckwitz, G.; Gerber, B.; Kreipe, H. -H.; Liedtke, C.; Marschner, N.; Moebus, V.; Scheithauer, H.; Schneeweiss, A.; Thomssen, C.; et al. (Geburtshilfe und Frauenheilkunde, 2015)
For the first time, this year's St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but - for logistical reasons - in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this year's votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility.
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Prognosis of Patients with Early Breast Cancer Receiving 5 Years vs 2 Years of Adjuvant Bisphosphonate Treatment: A Phase 3 Randomized Clinical Trial - Friedl, Thomas W. P.; Fehm, Tanja; Mueller, Volkmar; Lichtenegger, Werner; Blohmer, Jens; Lorenz, Ralf; Forstbauer, Helmut; Fink, Visnja; Bekes, Inga; Huober, Jens; Jueckstock, Julia; Schneeweiss, Andreas; et al. (JAMA Oncology, 2021)
Importance: Bisphosphonate treatment in patients with early breast cancer has become part of care, but the optimal treatment duration is still unclear. Objective: To compare 2 vs 5 years of zoledronate treatment following adjuvant chemotherapy in patients with early breast cancer. Design, Setting, and Participants: The SUCCESS A phase 3 multicenter randomized open-label clinical trial with a 2 × 2 factorial design enrolled 3754 patients from September 21, 2005, to March 12, 2007 (last patient out, May 7, 2014). Final data analysis was conducted from September 2019 to October 2020. In 250 German study centers, patients were eligible for participation in the SUCCESS A trial if they had either node-positive or high-risk node-negative (defined as at least 1 of the following: tumor size ≥ pT2, histologic grade 3, negative hormone receptor status, or age ≤35 years) primary invasive breast cancer. Interventions: Patients were first randomized to adjuvant chemotherapy with 3 cycles of fluorouracil, epirubicin, and cyclophosphamide followed by 3 cycles of docetaxel with or without gemcitabine (not presented in this report). After chemotherapy, patients underwent a second randomization of 5 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years, followed by 4 mg intravenously every 6 months for 3 years) vs 2 years of zoledronate treatment (4 mg intravenously every 3 months for 2 years). Main Outcomes and Measures: The primary end point of the study was disease-free survival; secondary end points were overall survival, distant disease-free survival, and the incidence of skeletal-related adverse events. Survival times were measured from 2 years after the start of zoledronate treatment (landmark analysis). Results: Overall, data on 2987 patients were available for analysis; median age was 53 (range, 21-86) years. Disease-free survival, overall survival, and distant disease-free survival did not differ significantly between the 2 treatment arms (5 vs 2 years) as shown by adjusted multivariable Cox proportional hazards regression models (disease-free survival: hazard ratio [HR], 0.97; 95% CI, 0.75-1.25; P =.81; overall survival: HR, 0.98; 95% CI, 0.67-1.42; P =.90; distant disease-free survival: HR, 0.87; 95% CI, 0.65-1.18; P =.38). Adverse events were observed more often in the 5-year (46.2%) vs 2-year (27.2%) zoledronate treatment arm, which was particularly true for the skeletal-related events bone pain (5 years, 8.3% vs 2 years, 3.7%) and arthralgia (5 years, 5.1% vs 2 years, 3.1%). Conclusions and Relevance: The results of this phase 3 randomized clinical trial indicate that extending the zoledronate treatment beyond 2 years does not improve the prognosis of high-risk patients with early breast cancer receiving chemotherapy, suggesting that the currently recommended bisphosphonate treatment duration of 3 to 5 years could be reduced. Trial Registration: ClinicalTrials.gov Identifier: NCT02181101.
CRIS-Team Scopus Importer:2021-07-09

Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer - Fasching, Peter; Gaß, Paul; Häberle, Lothar; Volz, Bernhard; Hein, Alexander; Hack, Carolin; Lux, Michael P.; Jud, Sebastian; Hartmann, Arndt; Beckmann, Matthias; Slamon, Dennis J.; Erber, Ramona (Breast Cancer Research and Treatment, 2019)
Purpose: Several clinical trials have investigated the prognostic and predictive usefulness of molecular markers. With limited predictive value, molecular markers have mainly been used to identify prognostic subgroups in which the indication for chemotherapy is doubtful and the prognosis is favorable enough for chemotherapy to be avoided. However, limited information is available about which groups of patients may benefit from additional therapy. This study aimed to describe the prognostic effects of Ki-67 in several common subgroups of patients with early breast cancer. Methods: This retrospective study analyzed a single-center cohort of 3140 patients with HER2−, hormone receptor-positive breast cancer. Five-year disease-free survival (DFS) rates were calculated for low (< 10%), intermediate (10–19%), and high (≥ 20%) Ki-67 expression levels, as assessed by immunohistochemistry, and for subgroups relative to age, body mass index, disease stage, tumor grade, and (neo-)adjuvant chemotherapy. It was also investigated whether Ki-67 had different effects on DFS in these subgroups. Results: The 5-year DFS rates for patients with low, intermediate, and high levels of Ki-67 expression were 0.90, 0.89, and 0.77, respectively. Ki-67 was able to further differentiate patients with an intermediate prognosis into different prognostic groups relative to common clinical parameters. Patients with stage II breast cancer had 5-year DFS rates of 0.84, 0.88, and 0.79 for low, intermediate, and high levels of Ki-67 expression. Ki-67 had different prognostic effects in subgroups defined by age and tumor grade. Conclusions: Ki-67 may help identify patients in intermediate prognostic groups with an unfavorable prognosis who may benefit from further therapy.
CRIS-Team Scopus Importer:2019-06-18
Keywords: Breast cancer; Ki-67; Molecular marker; Prognosis; Proliferation

Prognostic effect of low-level HER2 expression in patients with clinically negative HER2 status - Hein, Alexander; Hartkopf, Andreas D.; Emons, Julius; Lux, Michael P.; Volz, Bernhard; Taran, Florin Andrei; Overkamp, Friedrich; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Lüftner, Diana; et al. (European Journal of Cancer, 2021)
Purpose: Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods: PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results: Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions: We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.
CRIS-Team Scopus Importer:2021-08-06
Keywords: Advanced breast cancer; Antihormone therapy; Chemotherapy; HER2; HER2/neu; Lapatinib; Metastatic; Pertuzumab; TDM-1; Trastuzumab

Prognostic gene expression signature for high-grade serous ovarian cancer - Millstein, J.; Budden, T.; Goode, E. L.; Anglesio, M. S.; Talhouk, A.; Intermaggio, M. P.; Leong, H. S.; Chen, S.; Elatre, W.; Gilks, B.; Nazeran, T.; Volchek, M.; et al. (Annals of Oncology, 2020)
Background: Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Patients and methods: Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Results: Expression levels of 276 genes were associated with OS (false discovery rate < 0.05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0.001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2.35, 95% confidence interval (CI) 2.02–2.71; P < 0.001]. Median survival [HR (95% CI)] by gene expression score quintile was 9.5 (8.3 to –), 5.4 (4.6–7.0), 3.8 (3.3–4.6), 3.2 (2.9–3.7) and 2.3 (2.1–2.6) years. Conclusion: The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.
CRIS-Team Scopus Importer:2020-07-17
Keywords: formalin-fixed paraffin-embedded; gene expression; high-grade serous ovarian cancer; overall survival; prognosis

Prognostic Impact of Weight Change During Adjuvant Chemotherapy in Patients With High-Risk Early Breast Cancer: Results From the ADEBAR Study - Mutschler, Nikola S.; Scholz, Christoph; Friedl, Thomas W. P.; Zwingers, Thomas; Fasching, Peter; Beckmann, Matthias; Fehm, Tanja; Mohrmann, Svjetlana; Salmen, Jessica; Ziegler, Carola; Jaeger, Bernadette; Widschwendter, Peter; et al. (Clinical Breast Cancer, 2018)
In addition to established prognostic factors, individual lifestyle-associated factors, such as obesity, physical activity, and diet, seem to modulate the course of breast cancer. The aim of this analysis was to evaluate the influence of weight changes during adjuvant chemotherapy on outcome in a large multicenter prospectively randomized trial.The ADEBAR trial compares a sequential chemotherapy consisting of epirubicin/cyclophosphamide followed by docetaxel to an epirubicin/5-fluorouracil/cyclophosphamide regimen in patients with lymph node-positive early breast cancer. Body weight was measured before each cycle of chemotherapy. According to the relative weight change (>= 5%) between the first and the last cycle, patients were categorized into the weight gain, weight loss, or stable weight group. Overall survival (OS) and disease-free survival were assessed by univariate Kaplan-Meier and multivariate Cox regression analyses.Concise data from 1080 of 1493 participants who completed all cycles of chemotherapy were available for analysis. Of 307 patients (24.8%) whose weight changed by >= 5%, 120 patients (11.1%) lost and 187 (17.3%) gained weight. Multivariate analysis showed a significant independent effect of weight change on OS (P = .039), but not on disease-free survival (P = .111). Both weight change groups had a worse OS compared to patients with stable weight (weight gain: hazard ratio, 1.55; 95% confidence interval, 1.01-2.40; P = .047; weight loss: hazard ratio, 1.55; 95% CI, 0.97-2.47; P = .067).Weight change of > 5% during adjuvant chemotherapy in patients with high-risk early breast cancer is associated with poor OS.
EVALuna2:56149

Prognostic relevance of Ki-67 in the primary tumor for survival after a diagnosis of distant metastasis - Loehberg, Christian R.; Almstedt, Katrin; Jud, Sebastian; Haeberle, Lothar; Fasching, Peter; Hack, Carolin; Lux, Michael P.; Thiel, Falk; Schrauder, Michael G.; Brunner, Michaela; Bayer, Christian M.; Hein, Alexander; et al. (Breast Cancer Research and Treatment, 2013)
Prediction of the prognosis for metastatic breast cancer patients depends on molecular subtypes similar to those found in patients with primary breast cancer. Several studies have shown that estrogen receptor (ER) and progesterone receptor (PR) status determine the course of the disease and the prognosis. As Ki-67 helps to differentiate molecular subtypes in patients with primary breast cancer, the aim of this study was to assess the prognostic relevance of Ki-67 in the primary tumor in relation to its prognostic relevance for patients with metastatic breast cancer. A total of 467 patients with invasive breast cancer were identified in the database of a single breast cancer center, in whom Ki-67 had been assessed in tumor material from the breast at the time of the primary diagnosis and who had developed a metastasis at any time during the subsequent course. For these patients, tumor and patient characteristics were used to determine prognostic factors relative to overall survival after the diagnosis of distant metastases. Ki-67 was added to this model to investigate whether this might improve the prediction of overall survival. In the multivariate Cox model, age at diagnosis, body mass index, nodal status, tumor size, ER and PR status, and time from diagnosis to metastasis were identified as relevant prognostic factors. Adding Ki-67 to the model improved the prediction of overall survival. There was also a significant and relevant interaction with the PR status. In patients with a low-proliferation primary tumor, a high level of PR expression would indicate an extraordinarily good prognosis (HR 0.39; 95 % CI, 0.23-0.66). In patients with higher-proliferation primary tumors, PR status was not capable of differentiating prognostic groups. Ki-67 is useful in addition to known prognostic factors for breast cancer. It is able to indicate a group of women with a poorer prognosis, specifically in the group of patients with PR-positive breast cancer. © 2013 Springer Science+Business Media New York.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Ki-67; Metastatic breast cancer; Progesterone receptor; Prognosis; Proliferation

Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program - Müller, V.; Banys-Paluchowski, M.; Friedl, T. W.P.; Fasching, Peter; Schneeweiss, A.; Hartkopf, A.; Wallwiener, D.; Rack, B.; Meier-Stiegen, F.; Huober, J.; Rübner, Matthias; Hoffmann, O.; et al. (ESMO Open, 2021)
Background: Circulating tumor cells (CTCs) have been reported to predict clinical outcome in metastatic breast cancer (MBC). Biology of CTCs may differ from that of the primary tumor and HER2-positive CTCs are found in some patients with HER2-negative tumors. Patients and methods: Patients with HER2-negative MBC were screened for participation in DETECT III and IV trials before the initiation of a new line of therapy. Blood samples were analyzed using CELLSEARCH. CTCs were labeled with an anti-HER2 antibody and classified according to staining intensity (negative, weak, moderate, or strong staining). Results: Screening blood samples were analyzed in 1933 patients with HER2-negative MBC. As many as 1217 out of the 1933 screened patients (63.0%) had ≥1 CTC per 7.5 ml blood; ≥5 CTCs were detected in 735 patients (38.0%; range 1-35 078 CTCs, median 8 CTCs). HER2 status of CTCs was assessed in 1159 CTC-positive patients; ≥1 CTC with strong HER2 staining was found in 174 (15.0%) patients. The proportion of CTCs with strong HER2 staining among all CTCs of an individual patient ranged between 0.06% and 100% (mean 15.8%). Patients with estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors were more likely to harbor ≥1 CTC with strong HER2 staining. CTC status was significantly associated with overall survival (OS). Detection of ≥1 CTC with strong HER2 staining was associated with shorter OS [9.7 (7.1-12.3) versus 16.5 (14.9-18.1) months in patients with CTCs with negative-to-moderate HER2 staining only, P = 0.013]. In multivariate analysis, age, ER status, PR status, Eastern Cooperative Oncology Group performance status, therapy line, and CTC status independently predicted OS. Conclusion: CTC detection in patients with HER2-negative disease is a strong prognostic factor. Presence of ≥1 CTC with strong HER2 staining was associated with shorter OS, supporting a biological role of HER2 expression on CTCs.
CRIS-Team Scopus Importer:2021-12-17
Keywords: breast cancer; circulating tumor cell; HER2 status; liquid biopsy; survival

Prognostic relevance of the HER2 status of circulating tumor cells in metastatic breast cancer patients screened for participation in the DETECT study program - Muller, Volkmar; Banys-Paluchowski, Maggie; Friedl, Thomas W. P.; Fasching, Peter; Schneeweiss, Andreas; Hartkopf, Andreas; Wallwiener, Diethelm; Rack, Brigitte; Meier-Stiegen, Franziska; Huober, Jens; Rübner, Matthias; Hoffmann, Oliver; et al. (Cancer Research, 2021)
CRIS-Team WoS Importer:2021-03-26

Progression-free survival and overall survival in patients with advanced her2-positive breast cancer treated with trastuzumab emtansine (T-dm1) after previous treatment with pertuzumab - Michel, Laura L.; Hartkopf, Andreas D.; Fasching, Peter; Kolberg, Hans Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias; et al. (Cancers, 2020)
The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8–7.8); in second-line treatment, 7.7 months (95% CI: 2.8–11.0); in third-line, 3.4 months (95% CI: 2.3–not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2–NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.
CRIS-Team Scopus Importer:2020-10-30
Keywords: Advanced breast cancer; Chemotherapy; HER2 c-erbB2; HER2/neu; Metastatic; Pertuzumab; T-DM1; Trastuzumab

PROTEIN SURFACE SIGNATURE ON SERUM EXTRACELLULAR VESICLES FOR NON-INVASIVE DETECTION OF TUMOR PROGRESSION IN GLIOBLASTOMA PATIENTS - Tzaridis, Theophilos; Weller, Johannes; Bachurski, Daniel; Shakheri, Farhad; Schaub, Christina; Hau, Peter; Buness, Andreas; Schlegel, Uwe; Steinbach, Joachim; Seidel, Clemens; Goldbrunner, Roland; Schaefer, Niklas; et al. (NEURO-ONCOLOGY, 2021)
CRIS-Team WoS Importer:2022-03-04

Prototypic (18)F-Labeled Argininamide-Type Neuropeptide Y Y1R Antagonists as Tracers for PET Imaging of Mammary Carcinoma - Keller, Max; Maschauer, Simone; Brennauer, Albert; Tripal, Philipp; Koglin, Norman; Dittrich, Ralf; Bernhardt, Guenther; Kuwert, Torsten; Wester, Hans-Juergen; Buschauer, Armin; Prante, Olaf (ACS Medicinal Chemistry Letters, 2017)
The neuropeptide Y (NPY) Y1 receptor (Y1R) selective radioligand (R)-N(?)-(2,2-diphenylacetyl)-N(?)-[4-(2-[(18)F]fluoropropanoylamino)butyl]aminocarbonyl-N-(4-hydroxybenzyl)argininamide ([(18)F]23), derived from the high-affinity Y1R antagonist BIBP3226, was developed for imaging studies of Y1R-positive tumors. Starting from the argininamide core bearing amine-functionalized spacer moieties, a series of fluoropropanoylated and fluorobenzoylated derivatives was synthesized and studied for Y1R affinity. The fluoropropanoylated derivative 23 displayed high affinity (Ki = 1.3 nM) and selectivity toward Y1R. Radiosynthesis was accomplished via (18)F-fluoropropanoylation, yielding [(18)F]23 with excellent stability in mice; however, the biodistribution study revealed pronounced hepatobiliary clearance with high accumulation in the gall bladder (>100 %ID/g). Despite the unfavorable biodistribution, [(18)F]23 was successfully used for imaging of Y1R positive MCF-7 tumors in nude mice. Therefore, we suggest [(18)F]23 as a lead for the design of PET ligands with optimized physicochemical properties resulting in more favorable biodistribution and higher Y1R-dependent enrichment in mammary carcinom
EVALuna2:13870

Psychological Predictors of Acute Postoperative Pain after Hysterectomy for Benign Causes - Scheel, Jennifer; Sittl, Reinhard; Grießinger, Norbert; Strupf, Marion; Parthum, Andreas; Dimova, Violeta; Horn-Hofmann, Claudia; Thiel, Falk; Beckmann, Matthias; Lautenbacher, Stefan (Clinical Journal of Pain, 2016)
Psychological parameters have been shown to contribute significantly to the development of acute postoperative pain (APOP). For the prediction of APOP in chest malformation patients and cancer patients, we found pain-specific psychological predictors to be of higher relevance than general psychological predictors. The current study aims to further substantiate these findings.In a sample of 73 middle-aged hysterectomy patients, three predictor sets were assessed 1 day before surgery: attentional biases (towards pain-related, social threat, and positive words in a dot-probe task), pain-related emotions and cognitions (pain anxiety, pain catastrophizing, and pain hypervigilance), and affective state variables (depression and somatization). APOP intensity rated 2-3 days after surgery and analgesic consumption during the first 48 postoperative hours were used as outcome measures.APOP intensity ratings were significantly explained by their best single predictors in a multiple regression analysis: social threat words of the dot-probe task, pain anxiety, and somatization (14.7% of explained variance). When comparing standardized beta coefficients, pain-specific psychological predictors appeared to be of higher explanatory relevance than general psychological predictors. In contrast, analgesic consumption could not be significantly predicted by the psychological variables.Hysterectomy patients at risk for high APOP intensity could be characterized by the psychological variables used, whereas their predictive value for analgesic consumption was limited. The high predictive potency of pain-specific psychological variables should be considered for further improvement of pain management and prevention, because pain-specific variables like pain anxiety can be the target of focal psychological interventions when preparing for surgery.
EVALuna2:16734

Psychooncological counseling and treatment as part of the Comprehensive Cancer Center (CCC): Multicenter study to detect the psycho-oncological needs, indications and using - Buettner-Teleaga, A.; Weis, J.; Goerling, U.; Hornemann, B.; Erim, Yesim; Beckmann, Matthias; Senf, B.; Gresch, C.; Schulz-Kindermann, K.; Friedrich, H. -C.; Albus, C.; Geiser, F.; et al. (2016)
EVALuna2:24037

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic TNBC that expresses PD-L1 - Fasching, Peter; Huang, M.; Haiderali, A.; Pan, W.; Hu, P.; Chaudhuri, M.; De Tilleghem, C. Le Bailly; Cappoen, N.; O'Shaughnessy, J. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Q-TWiST analysis of pembrolizumab combined with chemotherapy as first-line treatment of metastatic triple-negative breast cancer that expresses PD-L1 - Huang, Min; O'Shaughnessy, Joyce; Haiderali, Amin; Pan, Wilbur; Hu, Peter; Chaudhuri, Mitashri; Le Bailly De Tilleghem, Celine; Cappoen, Nicolas; Fasching, Peter (European Journal of Cancer, 2022)
Objective: In the KEYNOTE-355 (KN355) trial, pembrolizumab in combination with chemotherapy demonstrated superior efficacy and manageable safety compared with chemotherapy alone in patients with previously untreated locally recurrent inoperable and metastatic triple-negative breast cancer (mTNBC) with PD-L1 positive (Combined Positive Score [CPS]≥ 10) tumours. This study aimed to evaluate the clinical benefits and risks of pembrolizumab measured by quality-adjusted survival in the trial population. Methods: The study used data from the final analysis of KN355. The Quality-adjusted Time Without Symptoms of disease progression or Toxicity of treatment (Q-TWiST) analysis was used to compare treatments of pembrolizumab plus chemotherapy versus chemotherapy alone. Patients’ survival time was partitioned into three health states — toxicity before disease progression (TOX), time without symptoms or toxicity before disease progression (TWiST), and relapse (REL). Utilities for these health states were estimated using EuroQol-5 Dimensions, 3 Levels (EQ-5D-3L) data collected in KN355. Q-TWiST was derived as the utility-weighted sum of the mean health state durations. Results: Patients randomised to pembrolizumab plus chemotherapy had 3.7 months greater Q-TWiST (relative gain of 18%; P = 0.003) compared to those randomised to chemotherapy at the median follow-up of 44 months, and 4.3 months greater Q-TWiST (relative gain of 20%; P = 0.004) at the maximum follow-up of 52 months. The Q-TWiST gain increased with longer follow-up time. Conclusions: Pembrolizumab plus chemotherapy was associated with statistically significant and clinically important improvement in Q-TWiST compared to chemotherapy in previously untreated PD-L1–positive mTNBC.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Metastatic triple-negative breast cancer; Pembrolizumab plus chemotherapy; Q-TWiST; Quality-adjusted survival

Qualitätssicherungsrichtlinie Früh- und Reifgeborene des Gemeinsamen Bundesausschusses als Qualitätsrisiko? Analyse zu Erfüllungsgrad und Konsequenzen in der Versorgung weiterer intensivpflichtiger Patienten sowie drohender Frühgeburten am Beispiel eines regionalen Verbund-Perinatalzentrums - Kleeberg, Markus; Beckmann, Matthias; Fusch, Christoph; Hanf, Volker; Kainer, Franz; Klinge, Jens; Koehler, Wolfgang; Morhart, Patrick; Schroth, Michael Andreas (Zeitschrift für Geburtshilfe und Neonatologie, 2020)
Background The quality guideline for care delivery to preterm and mature infants (QFR-RL) places high demands on perinatal centers. In this analysis, the degree of fulfillment was determined. Additionally, care delivery to further patient groups and sufficient nursing staff capacity for caredelivery to imminent preterm infants (FG) were evaluated. Methods A network of 4 perinatal centers (level 1) with about 10,000 births per year supplied the data on the ratio of 1:1/1:2-care infants,patients per nurse, and nursing staff capacity. This data was statistically evaluated by center, shift, and week day over a period of 5 months for compliance with QFR-RL and DGPM recommendations. Furthermore, imminent preterm infants were recorded and compared with available nursing staff capacity. Results In total, the QFR-RL was fulfilled in 88% of shifts (n=1,584). Only one center reached the required 95. The degree of fulfillment and the number of staff nurses declined from late to night shifts (p<0.001). The ratio of 1:1-care infants was significantly higher when demands were not fulfilled (p<0.001). Only 14.1 of imminent preterm infants could have been attended in accordance with the QFR-RL. Conclusion 1:1 care as well as lower nurse staffing in late and night shifts lead to non-fulfillment of requirements and poorer care delivery to other intensive care patients. This was also reflected in the lower degree of fulfillment of DGPM recommendations. Sufficient nursing staff capacity was rare with the consequence that it was almost impossible to deliver care to imminent preterm infants per the guideline.
CRIS-Team Scopus Importer:2020-11-06
Keywords: 1:1-Care; preterm infants care; quality guideline of care delivery of preterm and mature infants; quality of care; staffing ratio

Quality-adjusted survival with ribociclib plus fulvestrant (R plus F) versus placebo plus fulvestrant (P plus F) in postmenopausal women (PMW) HR+/HER2-advanced breast cancer (ABC) based on the MONALEESA-3 trial - Jerusalem, G.; Delea, T.; Martin Jimenez, M.; De Laurentiis, M.; Nusch, A.; Beck, J. T.; Chan, A.; Im, S-A.; Neven, P.; Lonshteyn, A.; Chandiwana, D.; Lanoue, B.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-06-26

Quality-Adjusted Survival with Ribociclib Plus Fulvestrant Versus Placebo Plus Fulvestrant in Postmenopausal Women with HR±HER2− Advanced Breast Cancer in the MONALEESA-3 Trial - Jerusalem, Guy; Delea, Thomas E.; Martin, Migule; De Laurentiis, Michelino; Nusch, Arnd; Beck, J. Thaddeus; Chan, Arlene; Im, Seock Ah; Neven, Patrick; Lonshteyn, Alexander; Chandiwana, David; Lanoue, Brad; et al. (Clinical Breast Cancer, 2022)
Background: MONALEESA-3 demonstrated an overall survival (OS) benefit for ribociclib plus fulvestrant (R+F) in postmenopausal women with hormone receptor (HR) positive, HER2 negative advanced breast cancer (ABC). This study estimated quality-adjusted (QA) survival outcomes for patients receiving R+F vs. placebo (P)+F in MONALEESA-3. Methods: Kaplan-Meier OS was partitioned into health states: (1) toxicity (TOX)=time spent with grade 3 –4 adverse events before progression (DP); (2) progression (PROG)=time between DP and death; and (3) time without symptoms or toxicity (TWiST)=time not in TOX or PROG. QA time was calculated by combining estimated mean time in each health state with treatment-group specific health-state utility values estimated using EQ-5D-5L questionnaire. Outcomes included QA progression-free survival (QAPFS), QAOS, and QA TWiST (Q-TWiST). Q-TWiST was calculated with health-state utility values for TOX and PROG defined relative to TWiST. Results: Mean PFS and OS were significantly greater with R+F vs. P+F (difference 0.56 and 0.19 years). Mean time in TOX and TWiST were greater with R+F; mean time in PROG was greater with P+F. QAPFS was 0.45 years (95% CI 0.27 –0.63) greater with R+F than P+F (P <.001). QAOS was numerically greater with R+F vs. P+F (0.16 years, 95% CI 0.07 –0.45, P = .0569). Q-TWiST was 0.23 years greater with R+F (95% CI 0.07 –0.45, P = .0069). In a sensitivity analysis using an estimate of disutility for PROG, the difference in QAOS was 0.23 years (95% CI 0.08 –0.41, P = .0022). Conclusion: R+F in postmenopausal women with HR+/HER2- ABC improves QAPFS, resulting in clinically important improvements in Q-TWiST and may improve QAOS.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Breast cancer; Fulvestrant; Postmenopausal; Quality of life; Ribociclib; Survival

Quality assurance and improvement in oncology using guideline-derived quality indicators - results of gynaecological cancer centres certified by the German cancer society (DKG) - Griesshammer, Ellen; Wesselmann, S.; Beckmann, Matthias; Dannecker, C.; Wagner, U.; Sibert, N. T.; Armbrust, R.; Sehouli, J. (Journal of Cancer Research and Clinical Oncology, 2022)
Purpose Based on the example of Gynaecological Cancer Centres (GCCs) certified by the German Cancer Society, this study evaluates the results of medical-guideline-derived quality indicators (QIs) for cervical cancer (CC) and ovarian cancer (OC), examines the development of indicator implementation over time as well as the status of guideline-compliant care and identifies improvement measures. Methods QI results for patients with CC and OC treated in GCCs between 2015 and 2019 are analysed. The median, overall proportion and standard deviation of each QI were calculated. Two-sided Cochran-Armitage tests were applied. Results QIs are divided into two categories: process-organization (PO-QIs) and treatment-procedures (TP-QIs), to allow a differentiated analysis for identifying improvement measures. PO-QIs that reflect the implementation of processes and structures show a high degree of application. PO-QIs have a tremendous influence on the quality of care and are easy to implement through SOPs. TP-QIs report on treatments that are performed in the GCC. TP-QIs that report on systemic therapies reach a plateau where the guideline is known, but patient-related-factors meaningfully prevent further increase. TP-QIs that report on surgical interventions fluctuate. The most relevant factors are practitioners' personal skills. Besides the discussion of results amongst peers during the audit, improvement measures could include surgical courses or coaching. Conclusion The analysis shows that a combination of different measures is necessary to anchor quality sustainably in health care and thus improve it.
CRIS-Team WoS Importer:2022-06-17
Keywords: Quality indicators; Quality assurance; Health service research; Certification

Quality of life and oncological outcome in endometrial cancer patients after vaginal brachytherapy: comparison of two dosing schemes - Papathemelis, Thomas; Scharl, Sophia; Hipp, Matthias; Scharl, Anton; Beckmann, Matthias; Lux, Michael P.; Koelbl, Oliver (Archives of Gynecology and Obstetrics, 2019)
Purpose: Vaginal brachytherapy reduces the risk of local recurrence and was shown to be equieffective in preventing vaginal vault recurrence, but less toxic compared to external-beam radiotherapy in a subset of high intermediate-risk endometrial cancer patients and is administered as single adjuvant treatment in those patients. Different radiotherapeutic approaches with various dosing schemes exist toward brachytherapy. The aim of this study was to compare the outcome and long-term quality of life after brachytherapy with two different high-dose-rate dosing schemes. Methods: Retrospective analysis was conducted of the recurrence and survival rates of 104 patients with endometrial cancer FIGO stage I–II that underwent adjuvant brachytherapy with three times 5 Gy or four times 5 Gy to the upper two-thirds of the vaginal vault in two different institutions between January 2010 and December 2013. Quality of life was assessed by EORTC QLQ-30 questionnaire and EN 24 module. Results: The vaginal vault recurrence rates were 4.9% and 5.0% for patients treated with 3 × 5 Gy and 4 × 5 Gy, respectively (p = 0.98). We did not observe a difference in pelvic recurrence (p = 0.96), overall survival (p = 0.33) or quality of life between the different radiotherapy regimens. Metastatic recurrence and the use of chemotherapy contribute to impairment on quality of life. Younger patients (< 70 years) reported worse emotional functioning (p = 0.02) and higher symptom scales of diarrhea (p = 0.01) and financial problems (p = 0.03). Sexual activity was lower in patients younger than 70 years (p = 0.05). Conclusions: Further prospective studies are needed to evaluate the effect of dosing schemes on recurrence rates and quality of life. Younger patients (< 70 years) seem to experience greater reduction in quality of life due to endometrial cancer diagnosis.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Adjuvant treatment; Brachytherapy; Endometrial cancer; Radiotherapy

Quality of Life and Treatment-Related Side Effects in Patients With HR+/HER2- Advanced Breast Cancer: Findings From a Multicountry Survey - Cardoso, Fatima; Rihani, Julie; Harmer, Victoria; Harbeck, Nadia; Casas, Ana; Rugo, Hope S.; Fasching, Peter; Moore, Adam; de Courcy, Joanna; Pathak, Purnima; Haftchenary, Sina; Aubel, Dawn; et al. (Oncologist, 2023)
BACKGROUND: Quality of life (QOL) is a critical factor in decision-making for advanced breast cancer (ABC). There is a need to improve how QOL and treatment-related side effects (SEs) that impact it are clinically assessed. We examined healthcare professionals' (HCPs') and patients' perspectives on the importance of QOL discussions and the impact of SEs on QOL in clinical settings. PATIENTS AND METHODS: A cross-sectional online survey was conducted (7/2020-5/2021) among oncologists, nurses, and patients with HR+/HER2- ABC in 7 countries. RESULTS: The survey was completed by 502 HCPs and 467 patients. Overall, 88% of oncologists and 49% of patients recalled QOL discussions at follow-up. In the first- through fourth-line (1L, 2L, 3L, and 4L) settings, respectively, 48%, 57%, 79%, and 85% of oncologists reported QOL was very important; 73% and 45% of patients receiving 1L and 2L treatment and 40% receiving 3L+ treatment indicated QOL was important. Patients reported that insomnia, anxiety, back pain, fatigue, diarrhea, hot flashes, low sexual interest, and loss of appetite had a moderate/severe impact on QOL. Of patients experiencing certain SEs, ≥64% did not discuss them with HCPs until there was a moderate/severe impact on QOL. In patients receiving a CDK4/6 inhibitor, SEs, including insomnia, diarrhea, back pain, and fatigue, had a moderate/severe impact on QOL. CONCLUSIONS: This survey discovered disconnects between HCPs and patients with ABC on the importance of QOL discussions and the impact of SEs on QOL. These data support the use of ABC-specific QOL questionnaires that closely monitor SEs impacting QOL.
CRIS-Team Scopus Importer:2023-10-20
Keywords: advanced breast cancer; physician/patient communication; qualitative research; quality of life; survey

Quality of life with talazoparib after platinum or multiple cytotoxic non-platinum regimens in patients with advanced breast cancer and germline BRCA1/2 mutations: patient-reported outcomes from the ABRAZO phase 2 trial - Hurvitz, S. A.; Quek, R. G. W.; Turner, N. C.; Telli, M. L.; Rugo, H. S.; Mailliez, A.; Ettl, J.; Grischke, E.; Mina, L. A.; Balmana, Judith; Fasching, Peter; Bhattacharyya, H.; et al. (European Journal of Cancer, 2018)
BACKGROUND: Talazoparib (1 mg/day) exhibited promising efficacy and safety in patients with advanced breast cancer during ABRAZO (NCT02034916); this study evaluated patient-reported outcomes (PROs). PATIENTS AND METHODS: ABRAZO is a two-cohort, two-stage, phase 2 study of talazoparib in patients with advanced breast cancer after a response to prior platinum-based therapy (cohort 1 [C1], n = 49) or ≥3 platinum-free cytotoxic-based regimens (cohort 2 [C2], n = 35). PROs were assessed on day 1 (baseline), every 6 weeks for an initial 24 weeks, and every 12 weeks thereafter until progression, using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) and its breast cancer module, QLQ-BR23. RESULTS: Global health status/quality of life (GHS/QoL) was maintained from baseline across all time points for both C1 and C2. For C1 and C2, median time to deterioration (TTD) of GHS/QoL (95% confidence interval [CI]) was 2.8 (2.1, 3.0) and 5.5 (4.2, 5.7) months, respectively. Median TTD for all QLQ-C30 functional scales for C1 and C2 ranged 2.1-3.1 months and 4.2-5.6 months, respectively; median TTD for all QLQ-BR23 symptom scales ranged 2.6-4.0 months and 4.2-5.6 months, respectively. There were no statistically significant differences in estimated overall change from baseline in the GHS/QoL scale for both cohorts (C1: -2.6 [95% CI, -7.8, 2.5]; C2: 1.2 [95% CI, -5.5, 8.0]). Significant overall improvements in the breast symptoms and arm symptoms and the future perspective of patients in C1 and C2 were observed, despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2). CONCLUSION: Despite the statistically significant and clinically meaningful overall deterioration among patients regarding their role functioning (in C1) and dyspnoea symptoms (in C2), patients in both C1 and C2 reported significant overall improvements in their breast symptoms, arm symptoms and future perspective, and their GHS/QoL was maintained from baseline.
EVALuna2:202806

Quantification of thyroid volume using 3-D ultrasound imaging - Kollorz, Eva Nicole Karin; Hahn, Dieter; Linke, Rainer; Goecke, Tamme W.; Hornegger, Joachim; Kuwert, Torsten (IEEE Transactions on Medical Imaging, 2008)
Ultrasound (US) is among the most popular diagnostic techniques today. It is non-invasive, fast, comparably cheap, and does not require ionizing radiation. US is commonly used to examine the size, and structure of the thyroid gland. In clinical routine, thyroid imaging is usually performed by means of 2-D US. Conventional approaches for measuring the volume of the thyroid gland or its nodules may therefore be inaccurate due to the lack of 3-D information. This work reports a semi-automatic segmentation approach for the classification, and analysis of the thyroid gland based on 3-D US data. The images are scanned in 3-D, pre-processed, and segmented. Several pre-processing methods, and an extension of a commonly used geodesic active contour level set formulation are discussed in detail. The results obtained by this approach are compared to manual interactive segmentations by a medical expert in five representative patients. Our work proposes a novel framework for the volumetric quantification of thyroid gland lobes, which may also be expanded to other parenchymatous organs. © 2006 IEEE.

RAD51B in Familial Breast Cancer - Pelttari, Liisa M.; Khan, Sofia; Vuorela, Mikko; Kiiski, Johanna I.; Vilske, Sara; Nevanlinna, Viivi; Ranta, Salla; Schleutker, Johanna; Winqvist, Robert; Kallioniemi, Anne; Doerk, Thilo; Bogdanova, Natalia V.; et al. (PLoS ONE, 2016)
Common variation on 14q24.1, close to RAD51B, has been associated with breast cancer: rs999737 and rs2588809 with the risk of female breast cancer and rs1314913 with the risk of male breast cancer. The aim of this study was to investigate the role of RAD51B variants in breast cancer predisposition, particularly in the context of familial breast cancer in Finland. We sequenced the coding region of RAD51B in 168 Finnish breast cancer patients from the Helsinki region for identification of possible recurrent founder mutations. In addition, we studied the known rs999737, rs2588809, and rs1314913 SNPs and RAD51B haplotypes in 44,791 breast cancer cases and 43,583 controls from 40 studies participating in the Breast Cancer Association Consortium (BCAC) that were genotyped on a custom chip (iCOGS). We identified one putatively pathogenic missense mutation c.541C>T among the Finnish cancer patients and subsequently genotyped the mutation in additional breast cancer cases (n = 5259) and population controls (n = 3586) from Finland and Belarus. No significant association with breast cancer risk was seen in the meta-analysis of the Finnish datasets or in the large BCAC dataset. The association with previously identified risk variants rs999737, rs2588809, and rs1314913 was replicated among all breast cancer cases and also among familial cases in the BCAC dataset. The most significant association was observed for the haplotype carrying the risk-alleles of all the three SNPs both among all cases (odds ratio (OR): 1.15, 95% confidence interval (CI): 1.11-1.19, P = 8.88 x 10-16) and among familial cases (OR: 1.24, 95% CI: 1.16-1.32, P = 6.19 x 10-11), compared to the haplotype with the respective protective alleles. Our results suggest that loss-of-function mutations in RAD51B are rare, but common variation at the RAD51B region is significantly associated with familial breast cancer risk.
EVALuna2:33327

Randomised, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE) - Kuemmel, Sherko; Paepke, Stefan; Huober, Jens; Schem, Christian; Untch, Michael; Blohmer, Jens Uwe; Eiermann, Wolfgang; Gerber, Bernd; Hanusch, Claus; Hilfrich, Joern; Jackisch, Christian; Schneeweiss, Andreas; et al. (European Journal of Cancer, 2017)
BACKGROUND: The GENEVIEVE study compared the pathological complete response (pCR) rate (ypT0/is ypN0/+) in patients with operable human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) treated with either cabazitaxel or paclitaxel. METHODS: GENEVIEVE was a prospective, multicentre, randomised, open-label, phase II study comparing the efficacy and the safety of four 3-weekly cycles cabazitaxel versus 12 weeks of paclitaxel given as neoadjuvant treatment. Primary end-point was the pCR rate defined as the complete absence of invasive carcinoma on histological examination of the breast irrespective of lymph node involvement (ypT0/is, ypN0/+) after the taxane treatment. Patients could receive an anthracycline-based therapy thereafter. RESULTS: Overall, 333 patients were randomised and started treatment with 74.7% and 83.2% of patients completing treatment in the cabazitaxel and paclitaxel arms, respectively. Patients in cabazitaxel arm had a significantly lower pCR rate compared to the paclitaxel arm (1.2% versus 10.8%; p = 0.001). A total of 42 (25.3%) patients in the cabazitaxel arm and 17 (10.2%) in the paclitaxel arm had at least one serious adverse event (p < 0.001). Dose reductions were observed in 9.6% patients in the cabazitaxel arm compared to 11.4% in the paclitaxel arm (p = 0.721). Main reason for dose reductions was non-haematological toxicities in 3.0% versus 7.8% (p = 0.087), respectively. CONCLUSIONS: The GENEVIEVE study showed no short-term effect of cabazitaxel in triple-negative or luminal B/HER2-negative primary BC, while there seemed to be no differences in drug exposure and patient compliance between the two arms. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT01779479.
EVALuna2:36185

Randomized, open-label, phase II study comparing the efficacy and the safety of cabazitaxel versus weekly paclitaxel given as neoadjuvant treatment in patients with operable triple negative or luminal B/HER2 normal breast cancer (GENEVIEVE) - Paepke, S.; Huober, J.; Sherko, K.; Eidtmann, H.; Untch, M.; Costa, S. Dan; Blohmer, J. U.; Eiermann, W.; Gerber, B.; Hanusch, C.; Hilfrich, J.; Jackisch, C.; et al. (2016)
EVALuna2:33541

RANK and RANKL Expression in Tumors of Patients with Early Breast Cancer - Behrens, Annika; Wurmthaler, Lena; Heindl, Felix; Gaß, Paul; Häberle, Lothar; Volz, Bernhard; Hack, Carolin; Emons, Julius; Erber, Ramona; Hartmann, Arndt; Beckmann, Matthias; Rübner, Matthias; et al. (Geburtshilfe und Frauenheilkunde, 2023)
Introduction The receptor activator of nuclear factor-κB (RANK) pathway was associated with the pathogenesis of breast cancer. Several studies attempted to link the RANK/RANKL pathway to prognosis; however, with inconsistent outcomes. We aimed to further contribute to the knowledge about RANK/RANKL as prognostic factors in breast cancer. Within this study, protein expression of RANK and its ligand, RANKL, in the tumor tissue was analyzed in association with disease-free survival (DFS) and overall survival (OS) in a study cohort of patients with early breast cancer. Patients and Methods 607 samples of female primary and early breast cancer patients from the Bavarian Breast Cancer Cases and Controls Study were analyzed to correlate the RANK and RANKL expression with DFS and OS. Therefore, expression was quantified using immunohistochemical staining of a tissue microarray. H-scores were determined with the cut-off value of 8.5 for RANK and 0 for RANKL expression, respectively. Results RANK and RANKL immunohistochemistry were assessed by H-score. Both biomarkers did not correlate (ρ = -0.04). According to molecular subtypes, triple-negative tumors and HER2-positive tumors showed a higher number of RANK-positive tumors (H-score ≥ 8.5), however, no subtype-specific expression of RANKL could be detected. Higher RANKL expression tended to correlate with a better prognosis. However, RANK and RANKL expression could not be identified as statistically significant prognostic factors within the study cohort. Conclusions Tumor-specific RANK and RANKL expressions are not applicable as prognostic factors for DFS and OS, but might be associated with subtype-specific breast cancer progression.
CRIS-Team Scopus Importer:2023-12-22
Keywords: breast cancer; immunohistochemistry; prognosis; RANK; RANKL

RANK Expression as an Independent Predictor for Response to Neoadjuvant Chemotherapy in Luminal-Like Breast Cancer: A Translational Insight from the GeparX Trial - Link, Theresa; Blohmer, Jens Uwe; Schmitt, Wolfgang D.; Kuhlmann, Jan Dominik; Just, Marianne; Untch, Michael; Stoetzer, Oliver J.; Fasching, Peter; Thill, Marc; Reinisch, Mattea; Schneeweiss, Andreas; Wimberger, Pauline; et al. (Clinical Cancer Research, 2023)
Purpose: The GeparX study investigated whether denosumab as add-on treatment to nab-paclitaxel–based neoadjuvant chemotherapy (NACT) with two different schedules (125 mg/m2 weekly vs. day 1, 8 every 22 days) may increase pathologic complete response (pCR) rate. The addition of denosumab to NACT did not improve pCR rates as recently published. In this study, we investigated whether receptor activator of nuclear factor-kappa B (RANK) expression, as part of the denosumab target pathway: (i) may retrospectively identify a subgroup of patients with additional clinical benefit of denosumab or (ii) may predict response to nab-paclitaxel NACT. Experimental Design: RANK protein was IHC-stained on pre-therapeutic core biopsies from patients of the GeparX study (n ¼ 667) with the antibody RANK/Envision System HRP (DAB) and was analyzed for the percentage of membranous RANK tumor cell staining (>5% RANKhigh vs. ≤5% RANKlow). Results: We could not identify any patient subgroup with differential response under denosumab add-on treatment in patients with RANKhigh expression [139/667, 20.8%; OR, 0.86; 95% confidence interval (CI), 0.44–1.68; P ¼ 0.667] or RANKlow expression (528/667 (79.2%) OR, 1.10; 95% CI, 0.78–1.56; P ¼ 0.589; Pinteraction ¼ 0.528). However, the pCR rate was higher in the RANKhigh subgroup compared with RANKlow (50% vs. 39%; OR, 1.52; 95% CI, 1.04–2.21; P ¼ 0.037). RANK expression constituted an independent predictor of response to NACT frequently in patients with luminal-like subtype (HRþ/HER2−; OR, 2.98; 95% CI, 1.30–6.79; P ¼ 0.010). No predictive value of RANK expression among the different nab-paclitaxel regimens was observed. Conclusion: We report RANK expression to be an independent predictive biomarker for response to NACT in patients with luminal-like breast cancer.
CRIS-Team Scopus Importer:2023-12-08

RANKL and OPG and their influence on breast volume changes during pregnancy in healthy women - Wunderle, Marius; Rübner, Matthias; Häberle, Lothar; Schwenke, Eva; Hack, Carolin; Bayer, Christian M.; Koch, Martin; Schwitulla, Judith; Schulz-Wendtland, Rüdiger; Kozieradzki, Ivona; Lux, Michael P.; Beckmann, Matthias; et al. (Scientific Reports, 2020)
Breast cancer risk is reduced by number of pregnancies and breastfeeding duration, however studies of breast changes during or after pregnancy are rare. Breast volume changes - although not linked to breast cancer risk - might be an interesting phenotype in this context for correlative studies, as changes of breast volume vary between pregnant women. Serum receptor activator of nuclear factor kappa B ligand (RANKL) and its antagonist osteoprotegerin (OPG) were measured prospectively before gestational week 12, and three-dimensional breast volume assessments were performed. A linear regression model including breast volume at the start of pregnancy, RANKL, OPG, and other factors was used to predict breast volume at term. The mean breast volume was 413 mL at gestational week 12, increasing by a mean of 99 mL up to gestational week 40. In addition to body mass index and breast volume at the beginning of pregnancy, RANKL and OPG appeared to influence breast volume with a mean increase by 32 mL (P = 0.04) and a mean reduction by 27 mL (P = 0.04), respectively. Linking the RANKL/RANK/OPG pathway with breast volume changes supports further studies aiming at analysing breast changes during pregnancy with regard to breast cancer risk.
CRIS-Team Scopus Importer:2020-03-31

Rare Case Report - Mucoepidermoid Carcinoma (MEC) of the Vulva - Dietl, Anna; Stübs, Frederik; Schulmeyer, Carla; Behrens, Annika; Hartmann, Arndt; Agaimy, Abbas; Beckmann, Matthias; Gaß, Paul (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Rare germline copy number variants (CNVs) and breast cancer risk - Dennis, Joe; Tyrer, Jonathan P.; Walker, Logan C.; Michailidou, Kyriaki; Dorling, Leila; Bolla, Manjeet K.; Wang, Qin; Ahearn, Thomas U.; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Arndt, Volker; et al. (Communications Biology, 2022)
Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
CRIS-Team Scopus Importer:2022-02-04

Real-world effectiveness of ribociclib 1 aromatase inhibitor, or endocrine monotherapy, or chemotherapy as first-line treatment in postmenopausal women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: The RIBANNA study - Fasching, Peter; Decker, T.; Guderian, G.; Heim, J.; Jackisch, C.; Lueck, H-J.; Lueftner, D.; Marme, F.; Reimer, T.; Woeckel, A. (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Real-world efficacy of ribociclib plus aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study - Wockel, Achim; Brucker, Cosima; Decker, Thomas; Falbrede, Jorg; Forstbauer, Helmut; Gohler, Thomas; Hoffmann, Oliver; Jackisch, Christian; Janssen, Jan; Kohler, Andreas; Ludtke-Heckenkamp, Kerstin; Luftner, Diana; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Reconstructing tumor history in breast cancer: signatures of mutational processes and response to neoadjuvant chemotherapy☆ - Denkert, C.; Untch, M.; Benz, S.; Schneeweiss, A.; Weber, K. E.; Schmatloch, S.; Jackisch, C.; Sinn, H. P.; Golovato, J.; Karn, T.; Marmé, F.; Link, T.; et al. (Annals of Oncology, 2021)
Background: Different endogenous and exogenous mutational processes act over the evolutionary history of a malignant tumor, driven by abnormal DNA editing, mutagens or age-related DNA alterations, among others, to generate the specific mutational landscape of each individual tumor. The signatures of these mutational processes can be identified in large genomic datasets. We investigated the hypothesis that genomic patterns of mutational signatures are associated with the clinical behavior of breast cancer, in particular chemotherapy response and survival, with a particular focus on therapy-resistant disease. Patients and methods: Whole exome sequencing was carried out in 405 pretherapeutic samples from the prospective neoadjuvant multicenter GeparSepto study. We analyzed 11 mutational signatures including biological processes such as APOBEC-mutagenesis, homologous recombination deficiency (HRD), mismatch repair deficiency and also age-related or tobacco-induced alterations. Results: Different subgroups of breast carcinomas were defined mainly by differences in HRD-related and APOBEC-related mutational signatures and significant differences between hormone-receptor (HR)-negative and HR-positive tumors as well as correlations with age, Ki-67 and immunological parameters were observed. We could identify mutational processes that were linked to increased pathological complete response rates to neoadjuvant chemotherapy with high significance. In univariate analyses for HR-positive tumors signatures, S3 (HRD, P < 0.001) and S13 (APOBEC, P = 0.001) as well as exonic mutation rate (P = 0.002) were significantly correlated with increased pathological complete response rates. The signatures S3 (HRD, P = 0.006) and S4 (tobacco, P = 0.011) were prognostic for reduced disease-free survival of patients with chemotherapy-resistant tumors. Conclusion: The results of this investigation suggest that the clinical behavior of a tumor, in particular, response to neoadjuvant chemotherapy and disease-free survival of therapy-resistant tumors, could be predicted by the composition of mutational signatures as an indicator of the individual genomic history of a tumor. After additional validations, mutational signatures might be used to identify tumors with an increased response rate to neoadjuvant chemotherapy and to define therapy-resistant subgroups for future therapeutic interventions.
CRIS-Team Scopus Importer:2021-03-05
Keywords: breast cancer; mutational signatures; neoadjuvant therapy; prognosis; response; whole exome sequencing

Reconstructive and Aesthetic Surgeries on the Female GenitaliaGuideline of the DGGG, DGPRAC, OEGGG and SGGG (S2k-Level, AWMF Registry No. 009/019, May 2022) - Beckmann, Matthias; Borkenhagen, Ada; Fahlbusch, Christine; Gold, Daniela; Hoffmann, Juergen; Löhrs, Bettina; Luze, Hanna; Mirastschijski, Ursula; O'Dey, Dan M.; Pöschke, Patrik; Remmel, Eugenia; Schaefer, Dirk; et al. (Geburtshilfe und Frauenheilkunde, 2023)
Aim This official guideline was coordinated and published by the German Society for Gynaecology and Obstetrics (DGGG), the German Society for Plastic, Reconstructive and Aesthetic Surgery (DGPRAC), the Austrian Society for Gynaecology and Obstetrics (OEGGG), and the Swiss Society for Gynaecology and Obstetrics (SGGG). The guideline aims to provide a consensus-based overview of reconstructive and aesthetic surgeries on female genitalia based on an evaluation of the relevant literature. Methods This S2k-guideline was developed by representative members from different medical professions on behalf of the guidelines commission of the DGGG, DGPRAC, OEGGG and SGGG using a structured consensus process. Recommendations Statements and recommendations on the epidemiology, aetiology, classification, symptoms, diagnosis, and treatment of acquired changes of the external genitalia are presented and special situations are discussed.
CRIS-Team Scopus Importer:2023-07-21
Keywords: aesthetic surgeries; female genital mutilation (FGM); female genitalia; guideline; reconstructive surgeries

Recording of the regional Origin Areas of Patients from the Molecular Tumor Board to Identify the "white Spots" in the Service Area - A joint Initiative of the Bavarian CCC WERA Alliance - Lueke, F.; Haller, F.; Utpatel, K.; Krebs, M.; Meidenbauer, Norbert; Scheiter, A.; Spörl, Silvia; Heudobler, D.; Keil, F.; Schubart, Christoph; Tögel, Lars; Einhell, S.; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-11-18

Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma. - Agaimy, Abbas; Clarke, Blaise A.; Kolin, David L.; Lee, Cheng-Han; Lee, Jen-Chieh; Mccluggage, W. Glenn; Pöschke, Patrik; Stöhr, Robert; Swanson, David; Turashvili, Gulisa; Beckmann, Matthias; Hartmann, Arndt; et al. (American Journal of Surgical Pathology, 2022)
With the widespread application of next-generation sequencing, the genetic landscape of uterine mesenchymal neoplasms has been evolving rapidly to include several recently identified fusion genes. Although chromosomal rearrangements involving the 10q22 and 17q21.31 loci have been reported in occasional uterine leiomyomas decades ago, the corresponding KAT6B::KANSL1 fusion has been only recently identified in 2 uterine tumors diagnosed as leiomyoma and leiomyosarcoma. We herein describe 13 uterine stromal neoplasms carrying a KAT6B::KANSL1 (n=11) and KAT6A::KANSL1 (n=2) fusion. Patient ages ranged from 33 to 81 years (median, 49 y). Tumor size was 2.6 to 23.5 cm (median, 8.2 cm). Nine tumors were myometrium-centered, and 3 had an intracavitary component. Original diagnoses were mostly low-grade endometrial stromal sarcoma (LG-ESS; 10 cases) with atypical features (limited CD10 expression, sex cord-like features, pericytic vasculature, and frequent myxoid changes). Treatment was hysterectomy±bilateral salpingo-oophorectomy (10), myomectomy (1), and curettage (2). Five patients were disease-free at 6 to 34 months, 3 (27%) died of disease at 2 to 47 months, and 3 were alive with disease at 2, 17, and 17 years. Histologically, most tumors showed variable overlap with LG-ESS, but they were generally well-circumscribed lacking the extensive permeative and angioinvasive growth typical of LG-ESS. They were composed of monotonous medium-sized oval and spindle cells arranged into diffuse sheets with prominent spiral-type arterioles and frequent pericytoma-like vascular pattern. Variable myxoid stromal changes were frequent. Mitotic activity ranged from 1 to >20 in 10 HPFs. Immunohistochemistry showed variable expression of CD10 (12/13), estrogen receptor (8/11), progesterone receptor (8/11), smooth muscle actin (9/11), desmin (4/12), h-caldesmon (2/10), calretinin (3/8), inhibin (1/7), WT1 (4/7), cyclin D1 (5/11; diffuse in only 1 case), and pankeratin (5/10). This series characterizes a KAT6B/A::KANSL1 fusion-positive uterine stromal neoplasm within the morphologic spectrum of LG-ESS but with atypical features. The relationship of these neoplasms to genuine LG-ESS remains unclear. This molecular subtype of uterine endometrial stromal sarcoma has the potential for an unfavorable clinical course despite the absence of widely invasive growth; nevertheless, analysis of more cases is necessary to delineate the phenotypic spectrum and biological potential of this tumor.
EVALuna2:504168

Reduction of Serious Adverse Events (SAE) under palbociclib treatment in patients using an interactive eHealth system - Schmidt, M.; Degenhardt, T.; Fasching, Peter; Lueftner, D.; Mueller, V.; Thomssen, C.; Schem, C.; Witzel, I.; Decker, T.; Tesch, H.; Kuemmel, S.; Uleer, C.; et al. (EUROPEAN JOURNAL OF CANCER, 2020)
CRIS-Team WoS Importer:2020-11-13

Reduction of Serious Adverse Events (SAE) under palbociclib treatment in patients using an interactive eHealth system - Schmidt, M.; Degenhardt, T.; Fasching, Peter; Lüftner, D.; Müller, V.; Thomssen, C.; Schem, C.; Witzel, I.; Decker, T.; Tesch, H.; Kümmel, S.; Uleer, C.; et al. (European Journal of Cancer, 2020)
CRIS-Team Scopus Importer:2020-10-16

Refined cut-off for TP53 immunohistochemistry improves prediction of TP53 mutation status in ovarian mucinous tumors: implications for outcome analyses - Kang, Eun Young; Cheasley, Dane; LePage, Cecile; Wakefield, Matthew J.; da Cunha Torres, Michelle; Rowley, Simone; Salazar, Carolina; Xing, Zhongyue; Allan, Prue; Bowtell, David D.L.; Mes-Masson, Anne Marie; Provencher, Diane M.; et al. (Modern Pathology, 2021)
TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MBOT with a higher risk of mortality.
CRIS-Team Scopus Importer:2021-02-05

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia - Spurdle, Amanda B.; Couch, Fergus J.; Parsons, Michael T.; Mcguffog, Lesley; Barrowdale, Daniel; Bolla, Manjeet K.; Wang, Qin; Healey, Sue; Schmutzler, Rita Katharina; Wappenschmidt, Barbara; Rhiem, Kerstin; Hahnen, Eric; et al. (Breast Cancer Research, 2014)
The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.
EVALuna2:9304

Regulation of murine placentogenesis by the retroviral genes Syncytin-A, Syncytin-B and Peg10 - Henke, Christine; Ruebner, Matthias; Faschingbauer, Florian; Stolt, Claus; Schäfer, Natascha; Lang, Nadine; Beckmann, Matthias; Strissel, Pamela; Strick, Reiner (Differentiation, 2013)
The murine placenta has a trichorial structure with two multinucleated syncytiotrophoblast (SCT) layers representing a barrier between the maternal and fetal blood system. Genes of endogenous retroviruses and retrotransposon-derived paternally expressed genes (Peg), remnants of past infections and integrations in the genome, have essential functions in placentogenesis. Previous studies showed that the envelope genes Syncytin-A and Syncytin-B were essential for cell-cell fusion of the SCT. The goal of this study was to analyze the temporal localization and expression of nine genes throughout placental development from embryonic day (E)8.5 to E18.5 using in situ-hybridization and absolute RNA-quantification. These included a comparison of previously characterized genes from the labyrinth Syncytin-A, Syncytin-B, Gcm1, the junctional zone PL-1, PL-2, Plf, Tpbpa with two further characterized genes Peg10 and Tpbpb. Syncytin-A and Syncytin-B RNA localized to SCT-I and SCT-II, respectively. Peg10 RNA localized to all extraembryonic tissues, specifically to the parietal and sinusoidal TGC of the labyrinth layer, which is in contact with SCT-I and the maternal blood. All three retroviral/retrotransposon-derived genes showed the highest expression at E16.5, but Peg10 with 188,917.1 molecules/ng cDNA was 208-fold and 106.8-fold higher expressed than Syncytin-A and Syncytin-B, respectively. Tpbpb localized to the junctional zone and showed the highest expression at E16.5 along with PL-2, Plf, Tpbpa, but not PL-1, which decreased in expression at E10.5. To investigate a role of Syncytin-A, Syncytin-B and Peg10 in cell-cell fusion, we established a cell culture system with fractionated primary trophoblasts from murine placentae. Culturing trophoblasts for up to 72h partly resembled trophoblast development in vivo according to the nine marker genes. Knockdown of Syncytin-A demonstrated a functional regulation of cell-cell fusion, where knockdown of Peg10 showed no involvement in cell fusion. Due to the expression of Peg10 in TGCs, we propose an essential functional role in the fetal-maternal blood system.
EVALuna2:4934

Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia - Auoragh, A.; Strnad, Vratislav; Ott, O. J.; Beckmann, Matthias; Fietkau, Rainer (Strahlentherapie und Onkologie, 2016)
Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented.Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly.The 5-year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder.Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects.
EVALuna2:18364

Relevance of tumour-infiltrating lymphocytes, PD-1 and PD-L1 in patients with high-risk, nodal-metastasised breast cancer of the German Adjuvant Intergroup Node–positive study - Noske, Aurelia; Möbus, Volker; Weber, Karsten; Schmatloch, Sabine; Weichert, Wilko; Köhne, Claus Henning; Solbach, Christine; Ingold Heppner, Barbara; Steiger, Katja; Müller, Volkmar; Fasching, Peter; Karn, Thomas; et al. (European Journal of Cancer, 2019)
Background: Immune cell infiltration in breast cancer is important for the patient's prognosis and response to systemic therapies including immunotherapy. We sought to investigate the prevalence of tumour-infiltrating lymphocytes (TILs)and their association with immune checkpoints such as programmed cell death 1 (PD-1)and programmed cell death ligand 1 (PD-L1)in high-risk, node-positive breast cancer of the adjuvant German Adjuvant Intergroup Node–positive (GAIN-1)trial. Patients and methods: We evaluated TILs by haematoxylin and eosin staining and PD-1 and PD-L1 (SP263 assay)expression by immunohistochemistry in 1318 formalin-fixed, paraffin-embedded breast carcinomas. The association of TILs with PD-1, PD-L1, molecular intrinsic subtypes, outcome and therapy regimens (dose-dense [dd]epirubicin, paclitaxel and cyclophosphamide [EPC]and dd epirubicin, cyclophosphamide, paclitaxel and capecitabine [EC-PwX])was statistically tested. Results: Overall TILs density was significantly associated with the expression of PD-1 and PD-L1 in immune cells (each p < 0.0001)and PD-L1 in tumour cells (p = 0.0051). TILs were more common in triple-negative breast cancer (TNBC)and human epidermal growth factor receptor 2 (HER2)HER2-positive tumours (each p < 0.0001). On multivariate Cox regression analyses, patients with breast cancer without TILs had an unfavourable disease-free survival (DFS)in the EPC arm compared with the EC-PwX arm (hazard ratio [HR]= 0.69 [0.44–1.06], p = 0.0915); but no differences were seen in tumours with TILs (HR = 1.24 [0.92–1.67], p = 0.1566, interaction p = 0.0336). PD-1–positive immune cells in TNBC were associated with a significantly better DFS (HR = 0.50 [0.25–0.99], p = 0.0457). PD-L1 expression had no impact on patient outcome. Conclusions: TILs predict the benefit of intensified ddEPC compared with ddEC-PwX therapy in node-positive, high-risk breast cancer. TILs, PD-1 and PD-L1 are linked to each other indicating tumour immunogenicity. Moreover, PD-1–positive immune cells have a positive prognostic impact in TNBC. Clinical trial: NCT00196872.
CRIS-Team Scopus Importer:2019-05-17
Keywords: Adjuvant; Breast cancer; PD-1; PD-L1; Prognosis; Therapy prediction; TILs

Reliability of an e-PRO Tool of EORTC QLQ-C30 for Measurement of Health-Related Quality of Life in Patients With Breast Cancer: Prospective Randomized Trial - Wallwiener, Markus; Matthies, Lina; Simoes, Elisabeth; Keilmann, Lucia; Hartkopf, Andreas D.; Sokolov, Alexander N.; Walter, Christina B.; Sickenberger, Nina; Wallwiener, Stephanie; Feisst, Manuel; Gaß, Paul; Fasching, Peter; et al. (Journal of Medical Internet Research, 2017)
BACKGROUND: Breast cancer represents the most common malignant disease in women worldwide. As currently systematic palliative treatment only has a limited effect on survival rates, the concept of health-related quality of life (HRQoL) is gaining more and more importance in the therapy setting of metastatic breast cancer. One of the major patient-reported outcomes (PROs) for measuring HRQoL in patients with breast cancer is provided by the European Organization for Research and Treatment of Cancer (EORTC). Currently, paper-based surveys still predominate, as only a few reliable and validated electronic-based questionnaires are available. Facing the possibilities associated with evolving digitalization in medicine, validation of electronic versions of well-established PRO is essential in order to contribute to comprehensive and holistic oncological care and to ensure high quality in cancer research. OBJECTIVE: The aim of this study was to analyze the reliability of a tablet-based measuring application for EORTC QLQ-C30 in German language in patients with adjuvant and (curative) metastatic breast cancer. METHODS: Paper- and tablet-based questionnaires were completed by a total of 106 female patients with adjuvant and metastatic breast cancer recruited as part of the e-PROCOM study. All patients were required to complete the electronic- (e-PRO) and paper-based versions of the HRQoL EORTC QLQ-C30 questionnaire. A frequency analysis was performed to determine descriptive sociodemographic characteristics. Both dimensions of reliability (parallel forms reliability [Wilcoxon test] and test of internal consistency [Spearman rho and agreement rates for single items, Pearson correlation and Kendall tau for each scale]) were analyzed. RESULTS: High correlations were shown for both dimensions of reliability (parallel forms reliability and internal consistency) in the patient's response behavior between paper- and electronic-based questionnaires. Regarding the test of parallel forms reliability, no significant differences were found in 27 of 30 single items and in 14 of 15 scales, whereas a statistically significant correlation in the test of consistency was found in all 30 single items and all 15 scales. CONCLUSIONS: The evaluated e-PRO version of the EORTC QLQ-C30 is reliable for patients with both adjuvant and metastatic breast cancer, showing a high correlation in almost all questions (and in many scales). Thus, we conclude that the validated paper-based PRO assessment and the e-PRO tool are equally valid. However, the reliability should also be analyzed in other prospective trials to ensure that usability is reliable in all patient groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT03132506; https://clinicaltrials.gov/ct2/show/NCT03132506 (Archived by WebCite at http://www.webcitation.org/6tRcgQuou).
EVALuna2:36167

Reliability of prenatal detection of X-linked hypohidrotic ectodermal dysplasia by tooth germ sonography - Hammersen, Johanna; Wohlfart, Sigrun; Goecke, Tamme W.; Köninger, Angela; Stepan, Holger; Gallinat, Ralph; Morris, Susan; Bücher, Katharina; Clarke, Angus; Wünsche, Stephanie; Beckmann, Matthias; Schneider, Holm; et al. (Prenatal Diagnosis, 2019)
Objective: In X-linked hypohidrotic ectodermal dysplasia (XLHED), dysfunction of ectodysplasin A1 (EDA1) due to EDA mutations results in malformation of hair, teeth, and sweat glands. Hypohidrosis, which can cause life-threatening hyperthermia, is amenable to intrauterine therapy with recombinant EDA1. This study aimed at evaluating tooth germ sonography as a noninvasive means to identify affected fetuses in pregnant carrier women. Methods: Sonography, performed at 10 study sites between gestational weeks 18 and 28, led to the diagnosis of XLHED if fewer than six tooth germs were detected in mandible or maxilla. The assessment was verified postnatally by EDA sequencing and/or clinical findings. Estimated fetal weights and postnatal weight gain of boys with XLHED were assessed using appropriate growth charts. Results: In 19 of 38 sonographic examinations (23 male and 13 female fetuses), XLHED was detected prenatally. The prenatal diagnosis proved to be correct in 37 cases; one affected male fetus was missed. Specificity and positive predictive value were both 100%. Tooth counts obtained by clinical examination corresponded well with findings on panoramic radiographs. We observed no weight deficits of subjects with XLHED in utero but occasionally during infancy. Conclusion: Tooth germ sonography is highly specific and reliable in detecting XLHED prenatally.
CRIS-Team Scopus Importer:2019-08-27

Repetitive Maturation of Oocytes From Non-Stimulated Xenografted Ovarian Tissue From a Prepubertal Patient Indicating the Independence of Human Ovarian Tissue - Raffel, Nathalie; Lotz, Laura; Hoffmann, Inge; Liebenthron, Jana; Söder, Stephan; Beckmann, Matthias; Dittrich, Ralf (Geburtshilfe und Frauenheilkunde, 2017)
Introduction: Modern anti-cancer strategies have distinctly increased survival rates; nevertheless, often accompanied by sterility. Currently, the only option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue and re-transplant frozen-thawed tissue to restore fertility after treatment. Our aim was to report the occurrence of repetitive antral follicle formation and oocyte maturation in a prepubescent ovarian tissue xenograft without exogenous hormone stimulation. Material and Methods: Frozen-thawed ovarian tissue from a 6-year-old patient suffering from nephroblastoma was xenotransplanted in oophorectomized severe combined immunodeficiency (SCID) mice to evaluate follicle development. Ergebnisse: Repetitive follicle development to the antral stage occurred in the same xenograft of prepubertal ovarian tissue without exogenous hormone administration; 37 days after retrieving a maturing oocyte (this first retrieval has been previously published), another, completely mature oocyte was harvested from the xenograft. Subsequent histological evaluation of the grafted tissue showed primordial follicles, nearly all stages of developing follicles, as well as large atretic ones. Many clusters with dormant primordial follicles were also present. Conclusion: Xenotransplanted prepubertal ovarian tissue has the potential for repetitive oocyte retrieval cycles without administering exogenous hormones. The results indicate that the human ovarian tissue might be able to synchronize the hypothalamus-hypophysis-axes of the mouse to the physiological human cycle; this should be investigated in future studies.
EVALuna2:34929

Replication of Epigenetic Postpartum Depression Biomarkers and Variation with Hormone Levels - Osborne, Lauren; Clive, Makena; Kimmel, Mary; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Judy, Jennifer; Meilman, Samantha; Braier, Aviva; Beckmann, Matthias; Kornhuber, Johannes; et al. (Neuropsychopharmacology, 2016)
DNA methylation variation at HP1BP3 and TTC9B is modified by estrogen exposure in the rodent hippocampus and was previously shown to be prospectively predictive of postpartum depression (PPD) when modeled in antenatal blood. The objective of this study was to replicate the predictive efficacy of the previously established model in women with and without a previous psychiatric diagnosis and to understand the effects of changing hormone levels on PPD biomarker loci. Using a statistical model trained on DNA methylation data from N=51 high-risk women, we prospectively predicted PPD status in an independent N=51 women using first trimester antenatal gene expression levels of HP1BP3 and TTC9B, with an area under the receiver operator characteristic curve (AUC) of 0.81 (95% CI: 0.69-0.92, p<5 × 10(-4)). Modeling DNA methylation of these genes in N=240 women without a previous psychiatric diagnosis resulted in a cross-sectional prediction of PPD status with an AUC of 0.81 (95% CI: 0.68-0.93, p=0.01). TTC9B and HP1BP3 DNA methylation at early antenatal time points showed moderate evidence for association to the change in estradiol and allopregnanolone over the course of pregnancy, suggesting that epigenetic variation at these loci may be important for mediating hormonal sensitivity. In addition both loci showed PPD-specific trajectories with age, possibly mediated by age-associated hormonal changes. The data add to the growing body of evidence suggesting that PPD is mediated by differential gene expression and epigenetic sensitivity to pregnancy hormones and that modeling proxies of this sensitivity enable accurate prediction of PPD.
EVALuna2:23791

Reply to "Response to: Dittrich et al.: Non-Embryo-Destructive Extraction of Pluripotent Embryonic Stem Cells - Overlooked Legal Prohibitions, Professional Legal Consequences and Inconsistencies in Patent Law" - Dittrich, Ralf; Beckmann, Matthias; Wuerfel, W. (Geburtshilfe und Frauenheilkunde, 2016)
EVALuna2:32938

Reproducibility of mRNA-Based Testing of ESR1, PGR, ERBB2, and MKI67 Expression in Invasive Breast Cancer-A Europe-Wide External Quality Assessment - Erber, Ramona; Hartmann, Arndt; Fasching, Peter; Rübner, Matthias; Stöhr, Robert; Beckmann, Matthias; Zentgraf, Miriam; Popp, Verena; Weidler, Jodi; Simon, Iris; Becker, Steffi; Hübner, Hanna; et al. (Cancers, 2021)
Simple Summary Four biomarkers [estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2], are used to stratify breast cancer (BC) into subtypes predictive of therapy response. In a Europe-wide external quality assessment, we compared performance of an mRNA-based method [Xpert(R) Breast Cancer STRAT4 (CE-IVD)] for determining ESR1, PGR, ERBB2, and MKI67 expression against the gold standard [immunohistochemistry (IHC)/HER2 in situ hybridization (ISH)]. The coordinating center (CC) and five European laboratories tested ten breast cancer samples. STRAT4 binary (positive or negative) results of each marker were compared with the gold standard. ESR1 and ERBB2 mRNA results were concordant with IHC/ISH in all single analyses. In contrast, PGR and MKI67 results were discordant in a few cases, which had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. STRAT4 assay may be a reproducible method. However, cases with expression values close to cut-offs should be carefully reviewed. Estrogen receptor (ER), progesterone receptor (PgR), Ki-67, and HER2 immunohistochemistry (IHC) together with HER2 in situ hybridization (ISH) are utilized to classify invasive breast cancer (IBC) into predictive molecular subtypes. As IHC evaluation may be hampered by analytical errors, gene expression assays could offer a reliable alternative. In this first Europe-wide external quality assessment (EQA) study, we investigated performance of mRNA-based Xpert(R) Breast Cancer STRAT4 (CE-IVD) in five European laboratories. The cohort comprised ten pre-therapy IBC core biopsies diagnosed in the coordinating center (CC). STRAT4 binary (positive or negative) mRNA results of each marker (ESR1, PGR, ERBB2, MKI67) were compared with the gold standard IHC/ISH performed by the CC. Sensitivity, specificity, and accuracy of ESR1 and ERBB2 mRNA were 100% for all samples. In contrast, PGR expression was falsely negative for one case by two sites and MKI67 falsely negative for two cases (respectively by four and one sites). These cases had STRAT4 expression values close to assay cut-offs and immunohistochemically presented heterogeneous low positive PgR and heterogeneous Ki-67. Our EQA shows that STRAT4 mRNA assay may be a reproducible method to evaluate ER, PgR, HER2, and Ki-67 status. However, cases with expression values close to assay cut-offs should be carefully reviewed.
CRIS-Team WoS Importer:2021-10-08

Reproductive profiles and risk of breast cancer subtypes: a multi-center case-only study - Brouckaert, Olivier; Rudolph, Anja; Laenen, Annouschka; Keeman, Renske; Bolla, Manjeet K.; Wang, Qin; Soubry, Adelheid; Wildiers, Hans; Andrulis, Irene L.; Arndt, Volker; Beckmann, Matthias; Benitez, Javier; et al. (Breast Cancer Research, 2017)
BACKGROUND: Previous studies have shown that reproductive factors are differentially associated with breast cancer (BC) risk by subtypes. The aim of this study was to investigate associations between reproductive factors and BC subtypes, and whether these vary by age at diagnosis. METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years. RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p < 0.0001), but this effect was not apparent at a later FFTP. CONCLUSIONS: Our main findings suggest that parity is associated with TNBC across all ages at BC diagnosis, whereas the association with luminal HER2-like BC was present only for early onset BC.
EVALuna2:36119

Resilience, Fear of Progression and Psychosocial Distress in Patients with Breast Cancer and Gynecological Tumors Seeking a Second Opinion. - Krebs, Jessica; Wasner, Sonja; Egloffstein, Sainab; Lux, Michael P.; Morawa, Eva; Beckmann, Matthias; Erim, Yesim (Psychotherapie Psychosomatik Medizinische Psychologie, 2018)

Response and prognosis after neoadjuvant chemotherapy in 1,051 patients with infiltrating lobular breast carcinoma - Loibl, Sibylle; Volz, Cristina; Mau, Christine; Blohmer, Jens-Uwe; Costa, Serban D.; Eidtmann, Holger; Fasching, Peter; Gerber, Bernd; Hanusch, Claus; Jackisch, Christian; Kuemmel, Sherko; Huober, Jens; et al. (Breast Cancer Research and Treatment, 2014)
Invasive lobular carcinomas (ILC) show better clinical behaviour compared with other histological types, but significantly lower pathological complete response (pCR) rates after neoadjuvant chemotherapy (NACT). We investigated whether factors influencing pCR rate in ILC after NACT can be identified and whether clinical outcome is different. 9,020 breast cancer patients from nine German neoadjuvant trials with known histological type were pooled. 11.7 % of tumours were ILC. Endpoints were: pCR rate, surgery type and survival. ILC was associated with older age, larger tumour size, lymph node negativity, lower grade and positive hormone-receptor-status (HR). Patients with ILC achieved a significantly lower pCR rate compared with non-ILC patients (6.2 vs. 17.4 %, P < 0.001). The pCR rate was 4.2 % in ILC/HR+/G1-2, 7.0 % in ILC with either HR- or G3, and 17.8 % in ILC/HR-/G3. Mastectomy rate was higher in ILC compared with non-ILC patients irrespective of response to NACT (pCR: 27.4 vs. 16.6 %, P = 0.037 and non-pCR: 41.8 % vs. 31.5 %, P < 0.0001). Age and HR independently predicted pCR in ILC. In ILC patients, pCR did not predict distant disease free (DDFS) and loco-regional disease free survival (LRFS), but overall survival (OS). Non-pCR patients with ILC had significantly better DDFS (P = 0.018), LRFS (P < 0.0001) and OS (P = 0.044) compared with non-ILC patients. Patients with ILC had a low chance of obtaining a pCR and this is not well correlated with further outcome. The mastectomy rate was considerably high in ILC patients even after obtaining a pCR. We, therefore, suggest to offer NACT mainly to ILC patients with HR-negative tumours.
EVALuna2:17507

Response to di Cosimo, Torri, and Porcu - Trapp, Elisabeth; Janni, Wolfgang; Schindlbeck, Christian; Jückstock, Julia; Andergassen, Ulrich; Degregorio, Amelie; Alunni-Fabbroni, Marianna; Tzschaschel, Marie; Polasik, Arkadius; Koch, Julian G.; Friedl, Thomas W.P.; Fasching, Peter A.; et al. (Journal of the National Cancer Institute, 2019)
CRIS-Team Scopus Importer:2019-12-24

Response to "Letter to the Editor" by Federico Prefumo - Stumpfe, Florian M.; Faschingbauer, Florian (Archives of Gynecology and Obstetrics, 2019)
CRIS-Team WoS Importer:2019-11-22

Response to "screening depression during and after pregnancy using the EPDS" - Hein, Alexander; Fasching, Peter; Goecke, Tamme W. (Archives of Gynecology and Obstetrics, 2014)
EVALuna2:17514

Responsiveness of human neonates to the odor of 5alpha-androst-16-en-3-one: A behavorial paradox? - Loos, Helene; Doucet, Sèbastien; Soussignan, Robert; Hartmann, Constanze; Durand, Karine; Dittrich, Ralf; Sagot, Paul; Büttner, Andrea; Schaal, Benoist (Chemical Senses, 2014)
The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother’s skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discusse
UnivIS-Import:2015-04-14:Pub.2014.nat.dchph.llmch.respon
Keywords: Amniotic fluid; Androstenone; Aversion; Milk; Olfaction

Responsiveness of human neonates to the odor of 5α-androst-16-en-3-one: A behavioral paradox? - Loos, Helene M.; Doucet, Sèbastien; Soussignan, Robert; Hartmann, Constanze; Durand, Karine; Dittrich, Ralf; Sagot, Paul; Büttner, Andrea; Schaal, Benoist (Chemical Senses, 2014)
The odorous steroid 5α-androst-16-en-3-one (AND) occurs in numerous biological fluids in mammals, including man, where it is believed to play a chemocommunicative role. As AND was recently detected in milk and amniotic fluid, sensitivity and hedonic responses to this substance were assessed in human neonates. To this aim, respiration and facial expressions were recorded in 3-day-old newborns in response to aqueous solutions of AND, ranging from 500ng/mL to 0.5 fg/mL. Although analyses of respiratory rate did not lead to clear-cut results, the newborns changed their facial expressions at concentrations not detected by adults in a triangle test. Newborns displayed negative facial actions of longer duration to AND relative to an odorless control. Thus, AND may be considered to be offensive to newborns, which is a counterintuitive outcome as they are exposed to this compound in the womb (and it should therefore be familiar), in milk, and on the mother's skin surface (and it should therefore be conditioned as positive). Multiple reasons for this perceptual-behavioral paradox are discussed.<br

Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor plus (HR plus ) metastatic breast cancer (MBC) who have previously received a taxane - O'Shaughnessy, Joyce; Schwartzberg, Lee; Piccart, Martine; Rugo, Hope S.; Yardley, Denise A.; Cortes, Javier; Untch, Michael; Harbeck, Nadia; Wright, Gail S.; Bondarenko, Igor; Glaspy, John; Nowecki, Zbigniew; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Results of ovulation induction with pulsatile GnRH using a novel portable device (LutrePulse (R)) - Hildebrandt, T.; Bartnitzky, S.; Bauer, K.; Boppert, H.; Luckhaus, J.; Ristau, B. (2017)
EVALuna2:36174

Results of Stimulation Treatment through pulsatile GnRH Substitution by using an innovative, patient-controlled System (LutrePulse((R))) - Hildebrandt, Thomas; Lotz, Laura; Blum, Simon; Fahlbusch, C.; Heusinger, K.; Cupisti, S.; Dittrich, Ralf; Beckmann, Matthias; Antoniadis, Sophia (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Results of TRIO-14, a phase II, multicenter, randomized, placebo-controlled trial of carboplatin-paclitaxel versus carboplatin-paclitaxel-ganitumab in newly diagnosed epithelial ovarian cancer - Konecny, G. E.; Hendrickson, A. E.Wahner; Davidson, T. M.; Winterhoff, B. J.; Ma, S.; Mahner, S.; Sehouli, J.; Fasching, Peter; Feisel-Schwickardi, G.; Poelcher, M.; Roman, L. D.; Rody, A.; et al. (Gynecologic Oncology, 2021)
Purpose: Insulin-like growth factor (IGF) signaling is implicated in pathogenesis and chemotherapy resistance of epithelial ovarian cancer (EOC). We explored efficacy and safety of adding ganitumab, a monoclonal antibody targeting IGF-1R, to carboplatin/paclitaxel (CP) chemotherapy in patients with primary EOC. Design: Patients were randomly assigned to receive CP/ganitumab (18 mg/kg q3w) or CP/placebo for 6 cycles followed by 6 cycles of single agent ganitumab/placebo maintenance therapy as front-line therapy. Primary endpoint was progression free survival. Secondary endpoints were time to progression and overall survival. Pretreatment samples were prospectively collected for retrospective biomarker analyses. Results: 170 patients enrolled. 165 patients assessable for toxicity. Median PFS was 15.7 months with CP/ganitumab and 16.7 months with CP/placebo (HR 1.23; 95% CI 0.82–1.83, P = 0.313). All grade neutropenia (84.1% vs 71.4%), thrombocytopenia (75.3% vs 57.1%) and hyperglycemia (15.9% vs 2.6%) were more common in the ganitumab group compared to the placebo group. Ganitumab/placebo related serious adverse events were reported in 26.1% of the patients with ganitumab and in 6.5% with placebo. Non-progression related fatal events were more common with ganitumab (5 versus 2 patients). The ganitumab group experienced more dose delays which resulted in lower relative dose intensity of chemotherapy in the experimental group. In an exploratory model IGFBP2 expression was predictive of ganitumab response (treatment interaction; PFS, P = 0.03; OS, P = 0.01). Conclusion: Addition of ganitumab to CP chemotherapy in primary EOC did not improve PFS. Our results do not support further study of ganitumab in unselected EOC patients.
CRIS-Team Scopus Importer:2021-10-22
Keywords: Ganitumab; IGFR1 inhibitor; Insulin-like growth factor; Ovarian cancer; Targeted therapy

Retraction: Improving usability and pregnancy rates of a fertility monitor by an additional mobile application: Results of a retrospective efficacy study of Daysy and DaysyView app (Reproductive Health (2018)15 (37) DOI: 10.1186/s12978-018-0479-6) - Koch, Martin; Lermann, Johannes; Van De Roemer, Niels; Renner, Simone K.; Burghaus, Stefanie; Hackl, Janina; Dittrich, Ralf; Kehl, Sven; Oppelt, Patricia; Hildebrandt, Thomas; Hack, Caroline; Pöhls, Uwe G.; et al. (Reproductive Health, 2019)
The Editor-in-Chief is retracting this article [1]. After publication concerns were raised about the reliability of the estimates of contraceptive effectiveness for the Daysy device when being used together with the DaysyView app [2]. Independent post-publication peer review has confirmed that there are fundamental flaws in the methodology which mean that the conclusions are unreliable due to selection bias and the retrospective self-reporting of whether pregnancies were intentional. The authors do not agree with this retraction. In particular, the authors are of the opinion that the retrospective design of their underlying study is described and that the respective disadvantages are discussed transparently in this article.
CRIS-Team Scopus Importer:2019-05-28

Return of individual genomic research results within the PRAEGNANT multicenter registry study - Hübner, Hanna; Rübner, Matthias; Kurbacher, Christian; Hadji, Peyman; Hartkopf, Andreas D.; Lux, Michael P.; Huober, Jens; Uhrig, Sabrina; Taran, Florin Andrei; Overkamp, Friedrich; Tesch, Hans; Häberle, Lothar; et al. (Breast Cancer Research and Treatment, 2022)
Purpose: The PRAEGNANT study is a registry study for metastatic breast cancer patients, focusing on biomarker detection. Recently, within this study, genetic alterations in 37 breast cancer predisposition genes were analyzed and genetic findings were detected for 396 participants. The aim of this project was to return genetic results to the physicians and to analyze actions taken (e.g., disclosure of results to patients, validation of results, clinical impact, and impact on the patient’s quality of life) using a questionnaire. Methods: 235 questionnaires were sent out to the study centers, with each questionnaire representing one patient with a genetic finding. The questionnaire consisted of twelve questions in the German language, referring to the disclosure of results, validation of test results, and their impact on treatment decisions and on the patient’s quality of life. Results: 135 (57.5%) questionnaires were completed. Of these, 46 (34.1%) stated that results were returned to the patients. In 80.0% (N = 36) of cases where results were returned, the patient had not been aware of the finding previously. For 27 patients (64.3%), genetic findings had not been validated beforehand. All validation procedures (N = 15) were covered by the patients’ health insurance. For 11 (25.0%) patients, physicians reported that the research results influenced current or future decision-making on treatment, and for 37.8% (N = 17) the results influenced whether family members will be genetically tested. Conclusion: This study provides novel insights into the return of research results and into clinical and personal benefits of disclosure of genetic findings within a German registry.
CRIS-Team Scopus Importer:2022-12-02
Keywords: Breast cancer; Genetic testing; Incidental findings; Research results; Return of results

Revised German guidelines on the diagnosis and treatment of carcinoma of the uterine cervix-what's new for pathologists in 2021? - Horn, Lars-Christian; Beckmann, Matthias; Follmann, Markus; Koch, Martin C.; Nothacker, Monika; Poschel, Birgit; Stübs, Frederik; Schmidt, Dietmar; Hohn, Anne Kathrin (Pathologe, 2022)
In 2021, the 2015 German consensus guideline for the diagnosis and treatment of uterine cervical carcinoma was updated. The present article summarises the new recommendations for pathologists: the incorporation of the International Endocervical Adenocarcinoma Classification (IECC), which morphologically separates HPV-associated and non-HPV-associated adenocarcinomas, as well as the reporting of the prognostic relevant growth pattern of the adenocarcinoma of the endocervical subtype (Silva pattern). Histologically, multifocality has been defined as the presence of clearly invasive foci with a minimum distance between each focus of 0.2 cm. Because of its intratumoural heterogeneity, all carcinomas <= 2 cm in their largest dimension should be processed completely, and tumours > 2 cm should be processed with one block per centimetre of their greatest dimension. In cases of (radical) trachelectomy/hysterectomy, the distal vaginal resection margin and all parametrial tissue should be processed completely. Sentinel lymph nodes have to be processed completely by lamellation along its long axis in 0.2 cm intervals. Immunohistochemical ultrastaging is mandatory. Staging should be performed using the 2009 FIGO classification and 2017 TNM classification. Reporting the revised 2018 FIGO classification is optional. To date, molecular markers have not been relevant for prognostication and treatment decision making.
CRIS-Team WoS Importer:2022-03-04
Keywords: Cutting; Workup; Diagnostic

Ribecca - a phase 3b, multi-center, open label study for women with estrogen receptor positive, locally advanced or metastatic breast cancer treated with ribociclib (lee011) in combination with letrozole: Final results - Reinisch, Mattea; Nusch, Arndt; Decker, Thomas; Hartkopf, Andreas; Heinrich, Bernhard J.; Kurbacher, Christian M.; Fuchs, Roswitha; Tesch, Hans; Krabisch, Petra; Brucker, Sara Y.; Fehm, Tanja; Janni, Wolfgang; et al. (CANCER RESEARCH, 2021)
CRIS-Team WoS Importer:2021-03-26

Ribociclib plus fulvestrant for advanced breast cancer: Health-related quality-of-life analyses from the MONALEESA-3 study - Fasching, Peter; Beck, J. Thaddeus; Chan, Arlene; De Laurentiis, Michele; Esteva, Francisco J.; Jerusalem, Guy; Neven, Patrick; Pivot, Xavier; Bianchi, Giulia V.; Martin, Miguel; Chandiwana, David; Lanoue, Brad; et al. (BREAST, 2020)
Purpose: In the MONALEESA-3 Phase III trial of patients with hormone receptor–positive human epidermal growth factor receptor–negative advanced breast cancer, ribociclib plus fulvestrant significantly improved progression-free survival (PFS) and overall survival (OS). Here, we present patient-reported outcomes from the trial, including health-related quality of life (HRQOL). Methods: Patients were randomized (2:1) to receive ribociclib plus fulvestrant or placebo plus fulvestrant. Time to definitive 10% deterioration (TTD) from baseline in HRQOL (global health status [GHS] from the EORTC QLQ-C30 questionnaire) and pain (BPI-SF questionnaire) were assessed using Kaplan-Meier estimates; a stratified Cox regression model was used to estimate the hazard ratio (HR) and 95% CIs. Results: Deterioration ≥10% in the EORTC-QLQ-C30 GHS was observed in 33% of patients in the ribociclib group vs 34% of patients in the placebo (reference) group (HR for TTD ≥ 10% = 0.81 [95% CI, 0.62–1.1]). Similar findings were noted for TTD ≥5% (HR = 0.79 [95% CI, 0.61–1.0]) and TTD ≥15% (HR = 0.81 [95% CI, 0.60–1.08]). TTD ≥10% in emotional functioning (HR = 0.76 [95% CI, 0.57–1.01]) trended in favor of the ribociclib group, whereas results for fatigue and pain were similar between arms. TTD ≥10% in BPI-SF pain severity index score (HR = 0.77 [95% CI, 0.57–1.05]) and worst pain item score (HR = 0.81 [95% CI, 0.58–1.12]) trended in favor of ribociclib vs placebo. Conclusions: In addition to significantly prolonging PFS and OS compared with placebo plus fulvestrant, adding ribociclib to fulvestrant maintains HRQOL.
CRIS-Team Scopus Importer:2020-10-23
Keywords: Breast cancer; Metastatic; Patient-reported outcomes; Quality of life

Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival - Slamon, D. J.; Neven, P.; Chia, S.; Jerusalem, G.; De Laurentiis, M.; Im, S.; Petrakova, K.; Valeria Bianchi, G.; Martín, M.; Nusch, A.; Sonke, G. S.; De la Cruz-Merino, L.; et al. (Annals of Oncology, 2021)
Background: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). Patients and methods: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2− ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). Results: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug–drug interaction between ribociclib and fulvestrant or new safety signals were observed. Conclusions: This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2− ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy.
CRIS-Team Scopus Importer:2021-08-06
Keywords: advanced breast cancer; CDK4/6 inhibitor; overall survival; ribociclib

Risk factors for locoregional recurrence (LRR) after neoadjuvant chemotherapy: Pooled analysis of prospective neoadjuvant breast cancer (BC) trials - Werutsky, G.; Untch, M.; Hanusch, C.; Fasching, Peter; Blohmer, J. -U.; Seiler, S.; Denkert, C.; Tesch, H.; Jackisch, C.; Gerber, B.; Schneeweiss, A.; Link, T.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Risk of Ovarian Cancer and the NF-?B Pathway: Genetic Association with IL1A and TNFSF10 - Charbonneau, Bridget; Block, Matthew S.; Bamlet, William R.; Vierkant, Robert A.; Kalli, Kimberly R.; Fogarty, Zachary; Rider, David N.; Sellers, Thomas A.; Tworoger, Shelley S.; Poole, Elizabeth; Risch, Harvey A.; Salvesen, Helga B.; et al. (Cancer Research, 2014)
A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1? (IL1A) is both regulated by and able to activate NF-?B, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-?B pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted. Cancer Res; 74(3); 852-61. ©2013 AACR.
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Risk of postmenopausal hormone therapy and patient history factors for the survival rate in women with endometrial carcinoma - Hein, Alexander; Schneider, Michael; Renner, Stefan; Fasching, Peter; Fießler, Cornelia; Titz, Susanna; Hartmann, Arndt; Beckmann, Matthias; Thiel, Falk C. (Archives of Gynecology and Obstetrics, 2019)
Purpose: Postmenopausal hormone therapy (HT) is known to affect the development of hormone-dependent endometrial carcinoma (type I EC). Several studies on breast and ovarian carcinoma have shown that HT influences the molecular profile and prognostic behavior of these tumors. This study aimed to investigate the influence of prior HT and other risk factors on the prognosis in a cohort of patients with invasive endometrial carcinoma (EC). Methods: Among 525 patients diagnosed with EC between 1987 and 2010, 426 postmenopausal patients were identified. Information regarding HT was available in 287 of these patients, 78 of whom had a history of HT and 209 of whom did not. Both overall survival (OS) and progression-free survival (PFS) were analyzed. In addition to OS and PFS, risk factors such as age at diagnosis, postmenopausal HT, body mass index (BMI), diabetes mellitus, tumor stage, EC type (I or II), and recurrences were analyzed. Results: Relative to HT alone, women with EC and a history of HT had a longer survival than those with no HT. However, the Cox proportional hazards model showed that it was not HT itself, but rather other characteristics in the HT group that were causally associated with longer survival. Conclusions: Age (the older, the worse) and tumor stage (the higher, the worse) were significant influences on overall survival. Patients with HT also had lower BMIs, less diabetes, more type I EC, and fewer recurrences in comparison with the non-HT group. With regard to the PFS, it made no difference whether the patient was receiving HT.
CRIS-Team Scopus Importer:2020-02-21
Keywords: Endometrial carcinoma; Estrogen; Hormone replacement therapy; Hormone therapy; Overall survival; Progesterone; Prognosis; Risk factors

Risk, Prediction and Prevention of Hereditary Breast Cancer - Large-Scale Genomic Studies in Times of Big and Smart Data - Wunderle, Marius; Olmes, Gregor; Nabieva, Naiba; Häberle, Lothar; Jud, Sebastian; Hein, Alexander; Rauh, Claudia; Hack, Carolin; Erber, Ramona; Ekici, Arif Bülent; Hoyer, Juliane; Vasileiou, Georgia; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Over the last two decades genetic testing for mutations in BRCA1 and BRCA2 has become standard of care for women and men who are at familial risk for breast or ovarian cancer. Currently, genetic testing more often also includes so-called panel genes, which are assumed to be moderate-risk genes for breast cancer. Recently, new large-scale studies provided more information about the risk estimation of those genes. The utilization of information on panel genes with regard to their association with the individual breast cancer risk might become part of future clinical practice. Furthermore, large efforts have been made to understand the influence of common genetic variants with a low impact on breast cancer risk. For this purpose, almost 450 000 individuals have been genotyped for almost 500 000 genetic variants in the OncoArray project. Based on first results it can be assumed that - together with previously identified common variants - more than 170 breast cancer risk single nucleotide polymorphisms can explain up to 18% of familial breast cancer risk. The knowledge about genetic and non-genetic risk factors and its implementation in clinical practice could especially be of use for individualized prevention. This includes an individualized risk prediction as well as the individualized selection of screening methods regarding imaging and possible lifestyle interventions. The aim of this review is to summarize the most recent developments in this area and to provide an overview on breast cancer risk genes, risk prediction models and their utilization for the individual patient.
EVALuna2:34612

Robot-assisted liver resection - Aselmann, H.; Moeller, T.; Kersebaum, J. -N.; Egberts, J. H.; Croner, R.; Brunner, Michaela; Grützmann, Robert; Becker, T. (Chirurg, 2017)
Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.
EVALuna2:15283

Robotic-Assisted Liver Surgery - Croner, R.; Perrakis, Aristotelis; Grützmann, Robert; Hohenberger, Werner; Brunner, Michaela (Zentralblatt für Chirurgie, 2016)
The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of <= 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria.Malignant liver tumours were removed in 10 patients (71 %) and benign symptomatic liver tumors in 3 patients (21 %), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7 %) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21 %) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14 %). One patient (7 %) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively.Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.
EVALuna2:15228

Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures - Croner, Roland S.; Perrakis, Aristotelis; Hohenberger, Werner; Brunner, Michaela (Langenbecks Archives of Surgery, 2016)
Minimally invasive liver surgery is increasing worldwide. The benefit of the robot in this scenario is currently controversially discussed. We compared our robotic cases vs. laparoscopic and open minor hepatic resections and share the experience.From 2011 to 2015, ten patients underwent robotic and 19 patients underwent laparoscopic minor liver resections in the Department of Surgery, University Hospital Erlangen. These patients were compared to a case-matched control group of 53 patients. The perioperative prospectively collected data were analyzed retrospectively.Blood loss was significantly decreased in the robotic (306 ml) and laparoscopic (356 ml) vs. the open (903 ml) surgery group (p = 0.001). Mean tumor size was 4.1-4.8 cm in all groups (p = 0.571). Negative surgical margins were present in 94 % of the open and 100 % of the laparoscopic and robotic group (p = 0.882). Time for surgery was enlarged for robotic (321 min) vs. laparoscopic (242 min) and open (186 min) surgery (p = 0.001). Postoperative hospitalization was decreased after robotic (7 days) and laparoscopic (8 days) vs. open (10 days) surgery (p = 0.004). Total morbidity was 17 % for open, 16 % for laparoscopic, and 1 % for robotic cases (p = 0.345). Postoperative pain medication and elevation of liver enzymes were remarkably lower after minimally invasive vs. open procedures.Minimally invasive liver surgery can be performed safely for minor hepatic resections and should be considered whenever possible. Minor liver resections can be performed by standard laparoscopy equivalent to robotic procedures. Nevertheless, the robot adds a technical upgrade which may have benefits for challenging cases and major liver surgery.
EVALuna2:15231

Role of adipokines in embryo implantation - Jafari-Gharabaghlou, Davoud; Vaghari-Tabari, Mostafa; Oghbaei, Hajar; Lotz, Laura; Zarezadeh, Reza; Rezaei, Yeganeh Rastgar; Ranjkesh, Mahnaz; Nouri, Mohammad; Fattahi, Amir; Nikanfar, Saba; Dittrich, Ralf (Endocrine Connections, 2021)
Embryo implantation is a complex process in which multiple molecules acting together under strict regulation. Studies showed the production of various adipokines and their receptors in the embryo and uterus, where they can influence the maternal-fetal transmission of metabolites and embryo implantation. Therefore, these cytokines have opened a novel area of study in the field of embryo–maternal crosstalk during early pregnancy. In this respect, the involvement of adipokines has been widely reported in the regulation of both physiological and pathological aspects of the implantation process. However, the information about the role of some recently identified adipokines is limited. This review aims to highlight the role of various adipokines in embryo–maternal interactions, endometrial receptivity, and embryo implantation, as well as the underlying molecular mechanisms.
CRIS-Team Scopus Importer:2021-12-17
Keywords: Adipokine; Embryo implantation; Endometrium; Pregnancy; Trophoblast

Role of adipokines in the ovarian function: Oogenesis and steroidogenesis - Nikanfar, Saba; Oghbaei, Hajar; Rastgar Rezaei, Yeganeh; Zarezadeh, Reza; Jafari-gharabaghlou, Davoud; Nejabati, Hamid Reza; Bahrami, Zahra; Bleisinger, Nathalie; Samadi, Naser; Fattahi, Amir; Nouri, Mohammad; Dittrich, Ralf (Journal of Steroid Biochemistry and Molecular Biology, 2021)
Adipokines are mainly produced by adipose tissue; however, their expression has been reported in other organs including female reproductive tissues. Therefore, adipokines have opened new avenues of research in female fertility. In this regard, studies reported different roles for certain adipokines in ovarian function, although the role of other recently identified adipokines is still controversial. It seems that adipokines are essential for normal ovarian function and their abnormal levels could be associated with ovarian-related disorders. The objective of this study is to review the available information regarding the role of adipokines in ovarian functions including follicular development, oogenesis and steroidogenesis and also their involvement in ovary-related disorders.
CRIS-Team Scopus Importer:2021-03-12
Keywords: Adiponectin; Follicle; Granulosa cells; Leptin; Oocyte

Role of Pelvic Lymph Node Resection in Vulvar Squamous Cell Cancer: A Subset Analysis of the AGO-CaRE-1 Study - Woelber, Linn; Bommert, Mareike; Harter, Philipp; Prieske, Katharina; zu Eulenburg, Christine; Jueckstock, Julia; Hilpert, Felix; de Gregorio, Nikolaus; Iborra, Severine; Sehouli, Jalid; Ignatov, Atanas; Hillemanns, Peter; et al. (Annals of Surgical Oncology, 2021)
Background: As the population at risk for pelvic nodal involvement remains poorly described, the role of pelvic lymphadenectomy (LAE) in vulvar squamous cell cancer (VSCC) has been a matter of discussion for decades. Methods: In the AGO-CaRE-1 study, 1618 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB or higher primary VSCC treated at 29 centers in Germany between 1998 and 2008 were documented. In this analysis, only patients with pelvic LAE (n = 70) were analyzed with regard to prognosis and correlation between inguinal and pelvic lymph node involvement. Results: The majority of patients had T1b/T2 tumors (n = 47; 67.1%), with a median diameter of 40 mm (2–240 mm); 54/70 patients (77.1%) who received pelvic LAE had positive groin nodes. For 42 of these 54 patients, the number of affected groin nodes had been documented as a median of 3; 14/42 (33.3%) of these patients had histologically confirmed pelvic nodal metastases (median number of affected pelvic nodes 3 [1–12]). In these 14 patients, the median number of affected groin nodes was 7 (1–30), with a groin metastases median maximum diameter of 42.5 mm (12–50). Receiver operating characteristic analysis showed an area under the curve of 0.85, with 83.3% sensitivity and 92.6% specificity for the prediction of pelvic involvement in cases of six or more positive groin nodes. No cases of pelvic nodal involvement without groin metastases were observed. Prognosis in cases of pelvic metastasis was poor, with a median progression-free survival of only 12.5 months. Conclusion: For the majority of node-positive patients with VSCC, pelvic nodal staging appears unnecessary since a relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease.
CRIS-Team Scopus Importer:2021-04-02

rs2735383, located at a microRNA binding site in the 3'UTR of NBS1, is not associated with breast cancer risk - Liu, Jingjing; Loncar, Ivona; Collee, J. Margriet; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Andrulis, Irene L.; Barile, Monica; Beckmann, Matthias; Behrens, Sabine; Benitez, Javier; et al. (Scientific Reports, 2016)
NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
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rs495139 in the TYMS-ENOSF1 Region and Risk of Ovarian Carcinoma of Mucinous Histology - Kelemen, Linda E.; Earp, Madalene; Fridley, Brooke L.; Chenevix-Trench, Georgia; Fasching, Peter; Beckmann, Matthias; Ekici, Arif Bülent; Hein, Alexander; Lambrechts, Diether; Lambrechts, Sandrina; Van Nieuwenhuysen, Els; Vergote, Ignace; et al. (International Journal of Molecular Sciences, 2018)
Thymidylate synthase (TYMS) is a crucial enzyme for DNA synthesis. TYMS expression is regulated by its antisense mRNA, ENOSF1. Disrupted regulation may promote uncontrolled DNA synthesis and tumor growth. We sought to replicate our previously reported association between rs495139 in the TYMS-ENOSF1 3' gene region and increased risk of mucinous ovarian carcinoma (MOC) in an independent sample. Genotypes from 24,351 controls to 15,000 women with invasive OC, including 665 MOC, were available. We estimated per-allele odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression, and meta-analysis when combining these data with our previous report. The association between rs495139 and MOC was not significant in the independent sample (OR = 1.09; 95% CI = 0.97⁻1.22; p = 0.15; N = 665 cases). Meta-analysis suggested a weak association (OR = 1.13; 95% CI = 1.03⁻1.24; p = 0.01; N = 1019 cases). No significant association with risk of other OC histologic types was observed (p = 0.05 for tumor heterogeneity). In expression quantitative trait locus (eQTL) analysis, the rs495139 allele was positively associated with ENOSF1 mRNA expression in normal tissues of the gastrointestinal system, particularly esophageal mucosa (r = 0.51, p = 1.7 × 10-28), and nonsignificantly in five MOC tumors. The association results, along with inconclusive tumor eQTL findings, suggest that a true effect of rs495139 might be small.
EVALuna2:35118

S1 Guideline: Impairment of gonadal function after Cancer in Childhood and Adolescence - Borgmann-Staudt, Anja; Jantke, Andreas; Hinz, Stefan; Beckmann, Matthias; Dittrich, Ralf; Lotz, Laura; Balcerek, Magdalena (Klinische Pädiatrie, 2023)
A possible negative consequence of cancer treatment is the fertility impairment of young cancer survivors. However, most former patients express the wish to have biological children. Fertility-preserving measures are available and are - under certain circumstances - financed by health insurance. Separate information at the time of diagnosis and during follow-up care should be adapted to the individual risk and enable those affected to make a self-determined decision about cryopreservation of germ cells or germ cell tissue. Hyopgonadotropic hypogonadism can be treated by the pulsatile administration of gonadotropins. Affected individuals can be reassured. A health restriction of the offspring due to the cancer treatment is not to be expected, even after artificial insemination.
CRIS-Team Scopus Importer:2023-09-22
Keywords: childhood cancer; fertility impairment treatment; offspring health; patient education; self-determined decision

S3 guidelines on diagnostics and treatment of cervical cancer: Demands on pathology - Horn, L. -C.; Beckmann, Matthias; Follmann, M.; Koch, Matthias; Mallmann, P.; Marnitz, S.; Schmidt, D. (Pathologe, 2015)
Between 2011 and the end of 2014 the former consensus S2k guidelines for the diagnostics and treatment of cervical cancer were updated and upgraded to S3 level, methodologically based on the regulations of the German Cancer Society (DKG). The present article summarizes the relevant aspects for the sectioning, histopathological workup, diagnostics and reporting for the pathology of invasive cancer of the uterine cervix. The recommendations are based on the most recent World Health Organization (WHO) and TNM classification systems and consider the needs of the clinician for appropriate surgical and radiotherapeutic treatment of patients. Detailed processing rules of colposcopy-guided diagnostic biopsies, conization and trachelectomy as well as for radical hysterectomy specimens and lymph node resection (including sentinel lymph node resection) are given. In the guidelines deep stromal invasion in macroinvasive cervical cancer is defined for the first time as tumor infiltration of > 66% of the cervical stromal wall. Furthermore, morphological prognostic factors for microinvasive and macroinvasive cervical cancer are summarized.
EVALuna2:17602

S3 guidelines on the diagnosis and treatment of carcinoma of the endometrium : Requirements for pathology - Horn, L. -C.; Emons, G.; Aretz, Stefan; Bock, N.; Follmann, Markus; Lax, Sigurd F.; Nothacker, M.; Steiner, E.; Mayr, D.; Alt-Epping, Bernd; Aretz, Stefan; Bauerschmitz, Gerd; et al. (Pathologe, 2019)
The present article summarises the relevant aspects of the S3 guidelines on endometrioid carcinomas. The recommendations include the processing rules of fractional currettings as well as for hysterectomy specimens and lymph node resections (including sentinel lymph nodes). Besides practical aspects, the guidelines consider the needs of the clinicians for appropriate surgical and radiotherapeutic treatment of the patients. Carcinosarcomas are assigned to the endometrial carcinoma as a special variant. For the first time, an algorithmic approach for evaluation of the tumour tissue for Lynch syndrome is given. Prognostic factors based on morphologic findings are summarised.
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Sacral nerve stimulation for faecal incontinence in patients with sacral malformation - Brunner, Michaela; Cui, Z.; Matzel, Klaus (International Journal of Colorectal Disease, 2017)
Sacral nerve stimulation (SNS) is a common and effective treatment for faecal incontinence (FI), but accessibility of the sacral nerves is mandatory. In some cases, electrode placement fails for unknown reasons. A frequent cause could be sacral malformations, which have a high incidence (up to 24.1%) and can be unsuspected.We report two patients with FI consequent to congenital anorectal malformation and associated sacral malformation. Despite partial sacral agenesis, SNS was feasible in both. They benefitted greatly from SNS, with an improved ability to postpone the urge up to at least 15 min, reduced incontinence episodes (at least 50%), and significantly better quality of life.SNS may be feasible in patients with FI, even in the presence of sacral malformation. However, clinicians should be aware of the attendant technical difficulties. Preoperative imaging, preferably with MRI of the sacrum, is advisable. If the sacral spinal nerves are inaccessible technically, pudendal nerve stimulation could be considered, if anatomy permits.
EVALuna2:15239

Safety and immunogenicity of neoadjuvant treatment using WT1-immunotherapeutic in combination with standard therapy in patients with WT1-positive Stage II/III breast cancer: a randomized Phase I study - Higgins, M.; Curigliano, Giuseppe; Dieras, V.; Kuemmel, S.; Kunz, G.; Fasching, Peter; Campone, M.; Bachelot, T.; Krivorotko, P.; Chan, S.; Ferro, A.; Schwartzberg, L.; et al. (Breast Cancer Research and Treatment, 2017)
PURPOSE: This Phase I, multicenter, randomized study (ClinicalTrials.gov NCT01220128) evaluated the safety and immunogenicity of recombinant Wilms' tumor 1 (WT1) protein combined with the immunostimulant AS15 (WT1-immunotherapeutic) as neoadjuvant therapy administered concurrently with standard treatments in WT1-positive breast cancer patients. METHODS: Patients were treated in 4 cohorts according to neoadjuvant treatment (A: post-menopausal, hormone receptor [HR]-positive patients receiving aromatase inhibitors; B: patients receiving chemotherapy; C: HER2-overexpressing patients on trastuzumab-chemotherapy combination; D: HR-positive/HER2-negative patients on chemotherapy). Patients (cohorts A-C) were randomized (2:1) to receive 6 or 8 doses of WT1-immunotherapeutic or placebo together with standard neoadjuvant treatment in a double-blind manner; cohort D patients received WT1-immunotherapeutic in an open manner. Safety was assessed throughout the study. WT1-specific antibodies were assessed pre- and post-vaccination. RESULTS: Sixty-two patients were randomized; 60 received ≥ one dose of WT1-immunotherapeutic. Two severe toxicities were reported: diarrhea (cohort C; also reported as a grade 3 serious adverse event) and decreased left ventricular ejection fraction (cohort B; also reported as a grade 2 adverse event). Post-dose 4 of WT1-immunotherapeutic, 10/10 patients from cohort A, 0/8 patients from cohort B, 6/11 patients from cohort C, and 2/3 patients from cohort D were humoral responders. The sponsor elected to close the trial prematurely. CONCLUSIONS: Concurrent administration of WT1-immunotherapeutic and standard neoadjuvant therapy was well tolerated and induced WT1-specific antibodies in patients receiving neoadjuvant aromatase inhibitors. In patients on neoadjuvant chemotherapy or trastuzumab-chemotherapy combination, the humoral response was impaired or blunted, likely due to either co-administration of corticosteroids and/or the chemotherapies themselves.
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Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients (pts) with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant chemotherapy (NACT) - Marme, Frederik; Hanusch, Claus; Furlanetto, Jenny; Morris, Patrick; Link, Theresa; Denkert, Carsten; Fasching, Peter; Jackisch, Christian; Antolin, Silvia; Solbach, Christine; Aftimos, Philippe; Huober, Jens; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2022)
CRIS-Team WoS Importer:2022-12-16

Safety interim analysis (SIA) of the phase III postneoadjuvant SASCIA study evaluating sacituzumab govitecan (SG) in patients with primary HER2-negative breast cancer (BC) at high relapse risk after neoadjuvant treatment - Marme, F.; Hanusch, C.; Furlanetto, J.; Morris, P.; Link, T.; Denkert, C.; Fasching, Peter; Jackisch, C.; Antolin, S.; Solbach, C.; Aftimos, P.; Huober, J.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Salivary and hair cortisol as biomarkers of emotional and behavioral symptoms in 6–9 year old children - Golub, Yulia; Kuitunen-Paul, Sören; Panaseth, Kerstin; Stonawski, Valeska; Frey, Stefan; Steigleder, Ruth; Grimm, Jennifer; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; et al. (Physiology & behavior, 2019)
The aim of the present work is to investigate the association of salivary and cumulative cortisol levels with emotional and behavioral symptoms in a Franconian Cognition and Emotion Studies (FRANCES) general population cohort of 158 6- to 9 year old children. Salivary cortisol values were measured by one-day diurnal cortisol profile, whereas cumulative cortisol was estimated via one-month hair cortisol concentrations (rHCC). Nearly all significant associations of clinical symptoms with child cortisol indices were age dependent: We report emotional symptoms being associated with lower rHCC in younger children (6.06–7.54 years). In older children (7.55–9.41 years) behavioral problems were further associated with higher rHCC and lower salivary cortisol awakening responses. In summary, child clinical symptoms were stronger associated with markers of hair cortisol compared to salivary cortisol. To picture developmental mechanisms, we suggest longitudinal designs for cortisol measures of stress systems in children and adolescents.
CRIS-Team Scopus Importer:2019-07-02
Keywords: Behavioral symptoms; Emotional symptoms; FRANCES; Hair cortisol; HPA axis; Salivary cortisol

Saliva samples as a source of DNA for high throughput genotyping: an acceptable and sufficient means in improvement of risk estimation throughout mammographic diagnostics - Poehls, U. G.; Hack, Caroline; Ekici, Arif Bülent; Beckmann, Matthias; Fasching, Peter; Rübner, Matthias; Hübner, Hanna (European Journal of Medical Research, 2018)
BACKGROUND: Breast cancer screening programs seem to be an insufficient tool for women at high genetic risk for breast cancer. These women are not adequately monitored yet. Genetic testing may improve clearly the quality of breast cancer prevention programs. At present, blood samples are favored for obtaining high-quality DNA; however, DNA can also be obtained by collecting saliva. The aim of this study was, on the one hand, to determine whether saliva sampling is a practicable means to obtain sufficient quantity and quality of DNA and, on the other hand, whether it is accepted by patients throughout mammographic diagnostics. METHODS: 67 consecutive women with diagnostic need for mammography with or without a family history for breast cancer were asked for their basic willingness to undergo a genetic testing by saliva sample in addition to standard diagnostics. Saliva samples were analyzed in terms of DNA quantity and quality. RESULTS: 64 (95.6%) women agreed to provide a saliva sample; 3 of them denied participation. And even 63 out of 64 (98.4%) were interested in their specific results. 45 out of 64 samples contained a DNA concentration above 50 ng/µl, 12 samples were between 25 and 50 ng/µl and only 7 of them were under 25 ng/µl with the standard extraction procedure. CONCLUSION: A high number of patients seem to accept salvia samples as a risk assessment tool in breast diagnostics and are interested in their specific risk situation. At the same time, it could be demonstrated that it is an effective way to provide high-quality DNA for breast cancer gene analysis. However, it remains to be shown whether it would be possible to integrate it with the same acceptance in a nationwide breast cancer screening program.
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Sarcoma of the Uterus. Guideline of the DGGG and OEGGG (S2k Level, AWMF Register Number 015/074, February 2019) - Denschlag, Dominik; Ackermann, Sven; Battista, Marco Johannes; Cremer, Wolfgang; Egerer, Gerlinde; Follmann, Markus; Haas, Heidemarie; Harter, Philipp; Hettmer, Simone; Horn, Lars Christian; Juhasz-Boess, Ingolf; Kast, Karin; et al. (Geburtshilfe und Frauenheilkunde, 2019)
Aims This is an official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of how they should be managed clinically, and treatment requires a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is the result of the consensus of a representative interdisciplinary group of experts who carried out a systematic search of the literature on uterine sarcomas in the context of the guidelines program of the DGGG, OEGGG and SGGG. Members of the participating professional societies achieved a formal consensus after a moderated structured consensus process. Recommendations The consensus-based recommendations and statements include the epidemiology, classification, staging, symptoms, general diagnostic work-up and general pathology of uterine sarcomas as well as the genetic predisposition to develop uterine sarcomas. Also included are statements on the management of leiomyosarcomas, (low and high-grade) endometrial stromal sarcomas and undifferentiated uterine sarcomas and adenosarcomas. Finally, the guideline considers the follow-up and morcellation of uterine sarcomas and the information provided to patients.
CRIS-Team Scopus Importer:2019-11-05
Keywords: adenosarcoma; endometrial stromal sarcoma; leiomyosarcoma; morcellation; uterine sarcoma

Sarcoma of the UterusGuideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021) - Denschlag, Dominik; Ackermann, Sven; Battista, Marco Johannes; Cremer, Wolfgang; Egerer, Gerlinde; Fehr, Matthias; Follmann, Markus; Haase, Heidemarie; Harter, Philipp; Hettmer, Simone; Horn, Lars Christian; Juhasz-Boess, Ingolf; et al. (Geburtshilfe und Frauenheilkunde, 2022)
Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors. Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process. Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.
CRIS-Team Scopus Importer:2022-12-16
Keywords: adenosarcoma; endometrial stromal sarcoma; guideline; leiomyosarcoma; morcellation; uterine sarcoma

Sarcoma of the Uterus. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015/074, August 2015) - Denschlag, D.; Thiel, F. C.; Ackermann, S.; Harter, P.; Juhasz-Boess, I.; Mallmann, P.; Strauss, H. -G.; Ullrich, U.; Horn, L. -C.; Schmidt, D.; Vordermark, D.; Vogl, T.; et al. (Geburtshilfe und Frauenheilkunde, 2015)
Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Due to their rarity and their heterogeneous histopathology uterine sarcomas remain challenging tumors to manage and need a multidisciplinary approach. To our knowledge so far there is no evidence-based guideline on the appropiate management of these heterogeneous tumors. Methods: This S2k-guideline is the work of an representative committee of experts from a variety of different professions who were commissioned by the DGGG to carry out a systematic literature review of uterine sarcoma. Members of the participating scientific societies developed a structured consensus in a formal procedure. Recommendations: 1. The incidence and histopathologic classification of uterine sarcoma. 2. The clinical manifestations, diagnosis and staging of uterine sarcoma. 3. The management of leiomyosarcoma. 4. The management of endometrial stromal sarcoma and undifferentiated uterine sarcoma. 5. The management of adenosarcoma as well as carcinosarcomas. 6. The management of morcellated uterine sarcoma.
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SARS-CoV-2 Infection in Pregnancy - a Review of the Current Literature and Possible Impact on Maternal and Neonatal Outcome - Stumpfe, Florian; Titzmann, Adriana; Schneider, Michael; Stelzl, Patrick; Kehl, Sven; Fasching, Peter; Beckmann, Matthias; Enßer, Armin (Geburtshilfe und Frauenheilkunde, 2020)
In December 2019, cases of pneumonia of unknown cause first started to appear in Wuhan in China; subsequently, a new coronavirus was soon identified as the cause of the illness, now known as Coronavirus Disease 2019 (COVID-19). Since then, infections have been confirmed worldwide in numerous countries, with the number of cases steadily rising. The aim of the present review is to provide an overview of the new severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) and, in particular, to deduce from it potential risks and complications for pregnant patients. For this purpose, the available literature on cases of infection in pregnancy during the SARS epidemic of 2002/2003, the MERS (Middle East respiratory syndrome) epidemic ongoing since 2012, as well as recent publications on cases infected with SARS-CoV-2 in pregnancy are reviewed and reported. Based on the literature available at the moment, it can be assumed that the clinical course of COVID-19 disease may be complicated by pregnancy which could be associated with a higher mortality rate. It may also be assumed at the moment that transmission from mother to child in utero is unlikely. Breastfeeding is possible once infection has been excluded or the disease declared cured.
CRIS-Team Scopus Importer:2020-05-19
Keywords: 2019-nCoV; coronavirus; COVID-19; pregnancy; SARS-CoV-2

Sebaceous breast carcinoma: report of a rare histological special subtype - Wachter, David; Rauh, C.; Wenkel, Evelyn; Fasching, Peter; Beckmann, Matthias; Hartmann, Arndt (Pathologe, 2014)
We report on a case of sebaceous carcinoma of the breast as a rare histological special subtype of breast cancer. Because these tumors are uncommon, differential diagnostic considerations and the exclusion of Muir-Torre syndrome are emphasized. Finally possible mechanisms of development and therapeutic strategies for this carcinoma are discussed.
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Selective expression of sense and antisense transcripts of the sushi-ichi-related retrotransposon - derived family during mouse placentogenesis - Henke, Christine; Strissel, Pamela; Schubert, Maria-Theresa; Mitchell, Megan; Stolt, Claus; Faschingbauer, Florian; Beckmann, Matthias; Strick, Reiner (Retrovirology, 2015)
LTR-retrotransposons became functional neogenes through evolution by acquiring promoter sequences, regulatory elements and sequence modification. Mammalian retrotransposon transcripts (Mart1-9), also called sushi-ichi-related retrotransposon-homolog (SIRH) genes, are a class of Ty3/gypsy LTR-retroelements showing moderate homology to the sushi-ichi LTR-retrotransposon in pufferfish. Rtl1/Mart1 and Peg10/Mart2 expression in mouse placenta and demonstration of their functional roles during placental development exemplifies their importance in cellular processes. In this study, we analyzed all eleven mouse Mart genes from the blastocyst stage and throughout placentogenesis in order to gain information about their expression and regulation.Quantitative PCR, in situ hybridization (ISH) and immunoblotting showed various expression patterns of the 11 mouse Mart genes through different placental stages. Zcchc5/Mart3, Zcchc16/ Mart4 and Rgag1/Mart9 expression was undetectable. Rtl1/Mart1, Peg10/Mart2, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a gene expression was very low at the blastocyst stage. Later placental stages showed an increase of expression for Rtl1/Mart1, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a, the latter up to 1,489 molecules/ng cDNA at E9.5. From our recently published findings Peg10/Mart2 was the most highly expressed Mart gene. ISH demonstrated sense and antisense transcript co-localization of Rgag4/Mart5 to Cxx1a,b,c/Mart8b,c,a in trophoblast subtypes at the junctional zone, with an accumulation of antisense transcripts in the nuclei. To validate these results, we developed a TAG-aided sense/antisense transcript detection (TASA-TD) method, which verified sense and antisense transcripts for Rtl1/Mart1, Rgag4/Mart5 - Cxx1a,b,c/Mart8b,c,a. Except for Rtl1/Mart1 and Cxx1a,b/Mart8b,c all other Mart genes showed a reduced amount of antisense transcripts. Northern blot and 5' and 3' RACE confirmed both sense and antisense transcripts for Ldoc1/Mart7 and Cxx1a,b,c/Mart8b,c,a. Immunoblotting demonstrated a single protein throughout all placental stages for Ldoc1/Mart7, but for Cxx1a,b,c/Mart8b,c,a a switch occurred from a 57 kDa protein at E10.5 and E14.5 to a 25 kDa protein at E16.5 and E18.5.RNA and protein detection of mouse Mart genes support neo-functionalization of retrotransposons in mammalian genomes. Undetectable expression of Zcchc5/Mart3, Zcchc16/Mart4 and Rgag1/Mart9 indicate no role during mouse placentogenesis. Rgag4/Mart5 to Cxx1a,b,c/Mart8b,c,a gene expression support a role for differentiation from the ectoplacental cone. Mart antisense transcripts and protein alterations predict unique and complex molecular regulation in a time directed manner throughout mouse placentogenesis.
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Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells - Weigand, Annika; Boos, Anja; Tasbihi, Kereshmeh; Beier, Justus; Dalton, Paul D.; Schrauder, Michael; Horch, Raymund E.; Beckmann, Matthias; Strissel, Pamela; Strick, Reiner (Breast Cancer Research, 2016)
There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors.A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds.Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering.Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.
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Self-reported Improvement in Side Effects and Quality of Life With Integrative Medicine in Breast Cancer Patients - Hack, Carolin; Hackl, Janina; Huettner, Nina B. M.; Langemann, Hanna; Schwitulla, Judith; Dietzel-Drentwett, Svenja; Fasching, Peter; Beckmann, Matthias; Theuser, Anna-Katharin (Integrative Cancer Therapies, 2018)
PURPOSE: Although the demand from patients for integrative medicine is increasing, complementary medicine services are still quite heterogeneous and have not been incorporated into clinical routine. The aim of this study was to systematically evaluate improvements in side effects and quality of life associated with a hospital-based integrative medicine program in the modern breast cancer patient care setting. METHODS: In a cross-sectional study, integrative health counseling and treatment were evaluated in women with breast cancer. Over a 15-month period, data for 75 patients from an integrative medicine consultancy service with standardized operating procedures were collected at the University Breast Center for Franconia. At baseline, the patients answered a questionnaire on their medical history, symptoms, and the treatment goals they were hoping to achieve with integrative medicine. In the follow-up, patient-reported outcomes related to side effects of conventional cancer treatment and patients' quality of life were analyzed. RESULTS: Among 60 patients with the therapy goal of reducing the side effects of conventional treatment, 46 (76.7%) were successful. Among 57 patients hoping to improve disease-related quality of life, 46 (82%) reported success. Whereas patients with metastatic disease achieved a reduction in the side effects of conventional therapy, quality-of-life improvements were predominantly achieved by patients with a good treatment prognosis. CONCLUSIONS: Breast cancer patients benefit from the counseling and treatment provided with integrative medicine in all phases of tumor disease. Integrative treatment services should be included as part of patient care in clinical routine work to offer patients the maximum quality of care and safety with complementary therapies.
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Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics - Seuß, Hannes; Dankerl, Peter; Ihle, Matthias; Grandjean, Andrea; Hammon, Rebecca; Kaestle, Nicola; Fasching, Peter; Maier, Christian; Christoph, Jan; Sedlmayr, Martin; Uder, Michael; Hammon, Matthias; et al. (Röfo-Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren, 2017)
Purpose Projects involving collaborations between different institutions require data security via selective de-identification of words or phrases. A semi-automated de-identification tool was developed and evaluated on different types of medical reports natively and after adapting the algorithm to the text structure. Materials and Methods A semi-automated de-identification tool was developed and evaluated for its sensitivity and specificity in detecting sensitive content in written reports. Data from 4671 pathology reports (4105 + 566 in two different formats), 2804 medical reports, 1008 operation reports, and 6223 radiology reports of 1167 patients suffering from breast cancer were de-identified. The content was itemized into four categories: direct identifiers (name, address), indirect identifiers (date of birth/operation, medical ID, etc.), medical terms, and filler words. The software was tested natively (without training) in order to establish a baseline. The reports were manually edited and the model re-trained for the next test set. After manually editing 25, 50, 100, 250, 500 and if applicable 1000 reports of each type re-training was applied. Results In the native test, 61.3 % of direct and 80.8 % of the indirect identifiers were detected. The performance (P) increased to 91.4 % (P25), 96.7 % (P50), 99.5 % (P100), 99.6 % (P250), 99.7 % (P500) and 100 % (P1000) for direct identifiers and to 93.2 % (P25), 97.9 % (P50), 97.2 % (P100), 98.9 % (P250), 99.0 % (P500) and 99.3 % (P1000) for indirect identifiers. Without training, 5.3 % of medical terms were falsely flagged as critical data. The performance increased, after training, to 4.0 % (P25), 3.6 % (P50), 4.0 % (P100), 3.7 % (P250), 4.3 % (P500), and 3.1 % (P1000). Roughly 0.1 % of filler words were falsely flagged. Conclusion Training of the developed de-identification tool continuously improved its performance. Training with roughly 100 edited reports enables reliable detection and labeling of sensitive data in different types of medical reports. Key Points: · Collaborations between different institutions require de-identification of patients' data. · Software-based de-identification of content-sensitive reports grows in importance as a result of 'Big data'. · A de-identification software was developed and tested natively and after training. · The proposed de-identification software worked quite reliably, following training with roughly 100 edited reports. · A final check of the texts by an authorized person remains necessary. Citation Format · Seuss H, Dankerl P, Ihle M et al. Semi-automated De-identification of German Content Sensitive Reports for Big Data Analytics. Fortschr Röntgenstr 2017; 189: 661 - 671.
EVALuna2:14623

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping) - Schulz-Wendtland, Rüdiger; Harz, Markus; Meier-Meitinger, Martina; Brehm, Barbara; Wacker, Till; Hahn, Horst K.; Wagner, Florian; Wittenberg, Thomas; Beckmann, Matthias; Uder, Michael; Fasching, Peter; Emons, Julius (Journal of Surgical Oncology, 2017)
Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors.In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors.The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm(3) and 7,770 mm(3) were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them.3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.
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Serum carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: a biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial - Janning, M.; Mueller,; Vettorazzi, E.; Cubas-Cordova, M.; Gensch,; Ben Batalla,; Eulenburg, Zu C.; Schem, C.; Fasching, Peter; Schnappauf, B.; Karn, Thomas; Fehm, T.; et al. (2016)
EVALuna2:33318

Sex-specific association between prenatal androgenization (second-to-fourth digit length ratio) and frontal brain volumes in adolescents - Lenz, Bernd; Gerhardt, Sarah; Boroumand-Jazi, Rafat; Eichler, Anna; Buchholz, Verena Nadine; Fasching, Peter; Kornhuber, Johannes; Banaschewski, Tobias; Flor, Herta; Guldner, Stella; Prignitz, Maren; Nees, Frauke (European archives of psychiatry and clinical neuroscience, 2022)
Prenatal androgenization associates sex-dependently with behavior and mental health in adolescence and adulthood, including risk-taking, emotionality, substance use, and depression. However, still little is known on how it affects underlying neural correlates, like frontal brain control regions. Thus, we tested whether prenatal androgen load is sex-dependently related to frontal cortex volumes in a sex-balanced adolescent sample. In a cross-sectional magnetic resonance imaging study, we examined 61 adolescents (28 males, 33 females; aged 14 or 16 years) and analyzed associations of frontal brain region volumes with the second-to-fourth digit length ratio (2D:4D), an established marker for prenatal androgenization, using voxel-based morphometry in a region-of-interest approach. Lower 2D:4D (indicative of higher prenatal androgen load) correlated significantly with smaller volumes of the right anterior cingulate cortex (r-ACC; beta = 0.45) in male adolescents and with larger volumes of the left inferior frontal gyrus orbital part (l-IFGorb; beta = - 0.38) in female adolescents. The regression slopes of 2D:4D on the r-ACC also differed significantly between males and females. The study provides novel evidence that prenatal androgenization may influence the development of the frontal brain in a sex- and frontal brain region-specific manner. These effects might contribute to the well-known sex differences in risk-taking, emotionality, substance use, and depression. Future research is needed to elucidate the role of prenatal androgenization within the biopsychosocial model.
CRIS-Team WoS Importer:2022-12-23

Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study - Laube, Jelena S.; Auer, Matthias K.; Biedermann, Sarah V.; Schröder, Johanna; Hildebrandt, Thomas; Nieder, Timo O.; Briken, Peer; Fuss, Johannes (Journal of Sexual Medicine, 2020)
Background: One of the most prominent etiological theories of gender incongruence in trans women proposes a paraphilic erotic target location error (ie, autogynephilia) as a causal factor in gynephilic (ie, exclusively gynephilic and bisexual) trans women. We hypothesized that a paraphilic erotic target location should manifest itself in various aspects of sexual behavior, solitary and dyadic sexual desire, and psychosexual experience. Aim: To compare sexual behavior, sexual desire, and psychosexual experience of exclusively gynephilic and bisexual trans women with that of androphilic trans women to explore whether their sexuality differs substantially. Methods: Trans women diagnosed with gender dysphoria (Diagnostic and Statistical Manual of Mental Disorders–5) were recruited at 4 transgender healthcare centers in Germany. The present study analyzed items on sexual behavior, desire, and experience of a self-report questionnaire, collected as part of a cross-sectional multicenter study. Main Outcomes: Multiple aspects of sexuality were examined using self-constructed items. Sexual desire was measured using the Sexual Desire Inventory and psychosexual experience using the Multidimensional Sexuality Questionnaire. Results: Significantly more exclusively gynephilic than androphilic trans women reported a history of sexual arousal in relation to cross-dressing. However, little evidence was found that gynephilic and androphilic sexual desire, behavior, and psychosexual experience differ profoundly. Interestingly, a statistically non-significant trend indicated that gynephilic trans women who had not yet undergone gender affirming surgery showed the highest levels of sexual desire (solitary and dyadic), whereas the opposite was the case for androphilic trans women. Clinical Translation: Data of this study indicate that sexual orientation does not appear to be a good predicator for sexual behavior, desire, and psychosexual experience in trans women. Strengths and Limitations: We investigated sexual desire and experience using standardized and evaluated measures such as the Sexual Desire Inventory and Multidimensional Sexuality Questionnaire. Future studies with a larger sample size should investigate how different gender affirming medical intervention might have diverging influences on sexual behavior, desire, and experience. Conclusion: Ultimately, this study found little evidence for the hypothesis that sexual behavior, sexual desire, and psychosexual experience differ substantially in gynephilic (exclusively gynephilic and bisexual) and androphilic trans women. Laube JS, Auer M, Biedermann SV, et al. Sexual Behavior, Desire, and Psychosexual Experience in Gynephilic and Androphilic Trans Women: A Cross-Sectional Multicenter Study. J Sex Med 2020;XX:XXX–XXX.
CRIS-Team Scopus Importer:2020-03-20
Keywords: Autogynephilia; Gender Dysphoria; Gender Incongruence; Male To Female; Sexual Orientation; Transgender

Shared genetics underlying epidemiological association between endometriosis and ovarian cancer - Lu, Yi; Cuellar-Partida, Gabriel; Painter, Jodie N.; Nyholt, Dale R.; Morris, Andrew P.; Fasching, Peter A.; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; et al. (Human Molecular Genetics, 2015)
Epidemiological studies have demonstrated associations between endometriosis and certain histotypes of ovarian cancer, including clear cell, low-grade serous and endometrioid carcinomas. We aimed to determine whether the observed associations might be due to shared genetic aetiology. To address this, we used two endometriosis datasets genotyped on common arrays with full-genome coverage (3194 cases and 7060 controls) and a large ovarian cancer dataset genotyped on the customized Illumina Infinium iSelect (iCOGS) arrays (10 065 cases and 21 663 controls). Previous work has suggested that a large number of genetic variants contribute to endometriosis and ovarian cancer (all histotypes combined) susceptibility. Here, using the iCOGS data, we confirmed polygenic architecture for most histotypes of ovarian cancer. This led us to evaluate if the polygenic effects are shared across diseases. We found evidence for shared genetic risks between endometriosis and all histotypes of ovarian cancer, except for the intestinal mucinous type. Clear cell carcinoma showed the strongest genetic correlation with endometriosis (0.51, 95% CI = 0.18-0.84). Endometrioid and low-grade serous carcinomas had similar correlation coefficients (0.48, 95% CI = 0.07-0.89 and 0.40, 95% CI = 0.05-0.75, respectively). High-grade serous carcinoma, which often arises from the fallopian tubes, showed a weaker genetic correlation with endometriosis (0.25, 95% CI = 0.11-0.39), despite the absence of a known epidemiological association. These results suggest that the epidemiological association between endometriosis and ovarian adenocarcinoma may be attributable to shared genetic susceptibility loci.
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Shared heritability and functional enrichment across six solid cancers - Jiang, Xia; Finucane, Hilary K.; Schumacher, Fredrick R.; Schmit, Stephanie L.; Tyrer, Jonathan P.; Han, Younghun; Michailidou, Kyriaki; Lesseur, Corina; Kuchenbaecker, Karoline B.; Dennis, Joe; Conti, David V.; Casey, Graham; et al. (Nature Communications, 2019)
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r g = 0.57, p = 4.6 × 10 −8 ), breast and ovarian cancer (r g = 0.24, p = 7 × 10 −5 ), breast and lung cancer (r g = 0.18, p =1.5 × 10 −6 ) and breast and colorectal cancer (r g = 0.15, p = 1.1 × 10 −4 ). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
CRIS-Team Scopus Importer:2019-05-02

SHEAR STRESS-DEPENDENT EXPRESSION OF GLYPICAN-4 AND HEPARAN SULFATE IN DIFFERENT PRIMARY HUMAN ENDOTHELIAL CELLS - Hug, K.; Tauchi, M.; Raaz-Schrauder, Dorette; Stumpfe, F.; Achenbach, Stephan; Dietel-Schor, B.; Urschel, K. (ATHEROSCLEROSIS, 2019)
CRIS-Team WoS Importer:2019-09-10

Shear stress dependent expression of glypican-4 and heparan sulfate in human endothelial cells - Urschel, K.; Hug, K.; Raaz-Schrauder, Dorette; Stumpfe, F. M.; Tauchi, M.; Achenbach, Stephan; Dietel-Schor, B. (EUROPEAN HEART JOURNAL, 2018)
CRIS-Team WoS Importer:2019-03-15

Shifting cancer care towards Multidisciplinarity: the cancer center certification program of the German cancer society - Kowalski, Christoph; Graeven, Ullrich; Von Kalle, Christof; Lang, Hauke; Beckmann, Matthias; Blohmer, Jens-Uwe; Burchardt, Martin; Ehrenfeld, Michael; Fichtner, Jan; Grabbe, Stephan; Hoffmann, Hans; Iro, Heinrich; et al. (BMC Cancer, 2017)
BACKGROUND: Over the last decades numerous initiatives have been set up that aim at translating the best available medical knowledge and treatment into clinical practice. The inherent complexity of the programs and discrepancies in the terminology used make it difficult to appreciate each of them distinctly and compare their specific strengths and weaknesses. To allow comparison and stimulate dialogue between different programs, we in this paper provide an overview of the German Cancer Society certification program for multidisciplinary cancer centers that was established in 2003. MAIN BODY: In the early 2000s the German Cancer Society assessed the available information on quality of cancer care in Germany and concluded that there was a definite need for a comprehensive, transparent and evidence-based system of quality assessment and control. This prompted the development and implementation of a voluntary cancer center certification program that was promoted by scientific societies, health-care providers, and patient advocacy groups and based on guidelines of the highest quality level (S3). The certification system structures the entire process of care from prevention to screening and multidisciplinary treatment of cancer and places multidisciplinary teams at the heart of this program. Within each network of providers, the quality of care is documented using tumor-specific quality indicators. The system started with breast cancer centers in 2003 and colorectal cancer centers in 2006. In 2017, certification systems are established for the majority of cancers. Here we describe the rationale behind the certification program, its history, the development of the certification requirements, the process of data collection, and the certification process as an example for the successful implementation of a voluntary but powerful system to ensure and improve quality of cancer care. CONCLUSION: Since 2003, over 1 million patients had their primary tumors treated in a certified center. There are now over 1200 sites for different tumor entities in four countries that have been certified in accordance with the program and transparently report their results from multidisciplinary treatment for a substantial proportion of cancers. This led to a fundamental change in the structure of cancer care in Germany and neighboring countries within one decade.
EVALuna2:33190

Shifts in Macrophage as a prognostic Biomarker in Patients with luminal Breast Cancer - A Confirmatory Study - Schnellhardt, Sören; Segelhorst, Sarah; Erber, Ramona; Daniel, Christoph; Hartmann, Arndt; Fasching, Peter; Beckmann, Matthias; Fietkau, Rainer; Distel, Luitpold; Rübner, Matthias (STRAHLENTHERAPIE UND ONKOLOGIE, 2021)
CRIS-Team WoS Importer:2021-07-16

Short Report on the Commission Work Financing Commission - successful work continues! - Renner, Stefan; Wallwiener, Diethelm; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2016)
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Should Breast Cancer Surgery Be Done in an Outpatient Setting?: Health Economics From the Perspective of Service Providers - Formago, Margaret; Schrauder, Michael G.; Rauh, Claudia; Hack, Carolin; Jud, Sebastian; Hildebrandt, Thomas; Schulz-Wendtland, Rüdiger; Frentz, S.; Graubert, S.; Beckmann, Matthias; Lux, Michael P. (Geburtshilfe und Frauenheilkunde, 2017)
INTRODUCTION: The care of patients with breast cancer is extremely complex and requires interdisciplinary care in certified facilities. These specialized facilities provide numerous services without being correspondingly remunerated. The question whether breast cancer surgery should be performed in an outpatient setting to reduce costs is increasingly being debated. This study compares inpatient surgical treatment with a model of the same surgery performed on an outpatient basis to examine the potential financial impact. MATERIAL AND METHODS: A theoretical model was developed and the DRG fees for surgical interventions to treat primary breast cancer were calculated. A theoretical 1-day DRG was then calculated to permit comparisons with outpatient procedures. The costs of outpatient surgery were calculated based on the remuneration rates of the AOP (Outpatient Surgery) Contract and the EBM (Uniform Assessment Scale) and compared to the costs of the 1-day DRG. RESULTS: The DRG fee for both breast-conserving surgery and mastectomy is higher than the fee paid in the context of the EBM system, although the same procedures were carried out in both systems. If a hospital were to carry out breast-conserving surgery as an outpatient procedure, the fee would be € 1313.81; depending on the type of surgery, the hospital would therefore only receive between 39.20% and 52.82% of the DRG fee. This was the case even for a 1-day treatment. Compared to the real DRG fees the difference would be even more striking. CONCLUSION: Carrying out breast cancer surgery as an outpatient procedure would result in a significant shortfall of revenues. Additional services from certified centers, such as the interdisciplinary planning of treatment, psycho-oncological and social-medical care with the involvement of relatives, detailed documentation, etc., which are currently provided without surcharge or adequate remuneration, could no longer be maintained. The quality of processes and excellent results which have been achieved and ultimately the care given by certified facilities would be significantly at risk.
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Signal decomposition for X-ray dark-field imaging - Käppler, Sebastian; Bayer, Florian; Weber, Thomas; Maier, Andreas; Anton, Gisela; Hornegger, Joachim; Beckmann, Matthias; Fasching, Peter; Hartmann, Arndt; Heindl, Felix; Michel, Thilo; Oezguel, Gueluemser; et al. (MICCAI 2014, 2014)
Grating-based X-ray dark-field imaging is a new imaging modality. It allows the visualization of structures at micrometer scale due to small-angle scattering of the X-ray beam. However, reading darkfield images is challenging as absorption and edge-diffraction effects also contribute to the dark-field signal, without adding diagnostic value. In this paper, we present a novel–and to our knowledge the first–algorithm for isolating small-angle scattering in dark-field images, which greatly improves their interpretability. To this end, our algorithm utilizes the information available from the absorption and differential phase images to identify clinically irrelevant contributions to the dark-field image. Experimental results on phantom and ex-vivo breast data promise a greatly enhanced diagnostic value of dark-field image
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Simultaneous amniotic membrane patch in high-risk keratoplasty - Seitz, Berthold; Das, Sujata; Sauer, Rolf; Hofmann-Rummelt, Carmen; Beckmann, Matthias; Kruse, Friedrich (Cornea, 2011)
To analyze the short- and intermediate-term results of simultaneous transplantation of amniotic membrane with high-risk keratoplasty.Between January 2002 and February 2004, a simultaneous amniotic membrane patch was transplanted with penetrating keratoplasty in 16 eyes of 16 patients. In 13 eyes, a soft contact lens was applied afterward. Corneal perforation was present in 10 of 14 eyes with emergency keratoplasty. Five patients received systemic immunosuppressive medication for 4-6 months after penetrating keratoplasty.The amniotic membrane patch fell off after 8 ± 3 (range: 4-14) days without residual tissue except in 1 case. In 15 of 16 eyes, the epithelium was completely closed after 10 ± 8 (range: 4-30) days. In 3 eyes, recurrence of the epithelial defect occurred after 3-6 months. During a follow-up period of 18 ± 6 months, 13 of 16 corneal grafts were clear.Simultaneous amniotic membrane transplantation and penetrating keratoplasty may improve the prognosis of corneal graft in eyes with risk of epithelial healing problems.
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Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial - Kehl, Sven; Schelkle, A.; Thomas, A.; Puhl, A.; Meqdad, K.; Tuschy, B.; Berlit, S.; Weiss, C.; Bayer, C.; Heimrich, J.; Dammer, U.; Raabe, E.; et al. (Ultrasound in Obstetrics & Gynecology, 2016)
OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.
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Single Deepest Vertical Pocket or Amniotic Fluid Index as Evaluation Test for Predicting Adverse Pregnancy Outcome (SAFE Trial): A Multicenter, Open-Label, Randomized Controlled Trial EDITORIAL COMMENT - Kehl, Sven; Schelkle, A.; Thomas, A.; Puhl, A.; Meqdad, K.; Tuschy, B.; Berlit, S.; Weiss, C.; Bayer, C.; Heimrich, J.; Dammer, U.; Raabe, E.; et al. (Obstetrical & Gynecological Survey, 2016)
One of the important aspects of fetal well-being assessment is amniotic fluid volume, lack of which leads to oligohydramnios and consequently adverse perinatal outcomes. Amniotic fluid estimation by ultrasound can be performed by assessment of the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique. This study aimed to investigate the best technique for amniotic fluid volume estimation to predict adverse pregnancy outcomes in both high-and low-risk pregnancies. In a randomized controlled trial (RCT), participants from 4 hospitals in Germany were allocated randomly to AFI or SDP measurement (1: 1). Oligohydramnios was defined by an AFI 5 cm or less or by the absence of an SDP measuring less than 2 x 1 cm. The primary outcome measure was admission to a neonatal intensive care unit (NICU) following childbirth, and other outcome measures included perinatal death, oligohydramnios, labor induction (for oligohydramnios or without specific indication), umbilical artery pH less than 7.10, 5-minute Apgar score of less than 7, meconium-stained amniotic fluid, abnormal cardiotocography, need for fetal scalp blood sampling, assisted vaginal delivery (for fetal distress or without specified indication), and cesarean delivery (for and without fetal distress). Statistical analyses were performed using the Student t test, Mann-Whitney U test,.2 test, or Fisher exact test and a logistic regression analysis or a 2-way analysis of variance. There were fewer women with gestational diabetes and a previous cesarean delivery in the AFI group among the 1002 women analyzed. Women with a high-risk pregnancy were older, shorter, and more overweight than women with a low-risk pregnancy. Postnatal admission rates to the NICU (4.2% vs 5%; relative risk [ RR], 0.85; 95% confidence interval [ CI], 0.481.50) and rate of arterial pH less than 7.10 were similar between the 2 groups (1.6% vs 3%; RR, 0.54; 95% CI, 0.23-1.26). There weremore participants with oligohydramnios (9.8% vs 2.2%; RR, 4.51; 95% CI, 2.37-8.57), more labor inductions for oligohydramnios (12.7% vs 3.6%; RR, 3.50; 95% CI, 1.76-6.96), and higher occurrences of abnormal cardiotocography (32.3% vs 26.2%; RR, 1.23; 95% CI, 1.02-1.50) in the AFI group than in the SDP group. More cases of oligohydramnios and labor inductions for oligohydramnios were found in low-risk pregnancies measured by the AFI method than by the SDP technique, and a lower arterial pH was observed in the AFI group compared with the SDP group in high-risk pregnancies. The AFI technique increased the diagnosis rate of oligohydramnios without improvement in perinatal outcome; hence, the SDP technique is preferred over AFI especially in low-risk pregnancies.
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Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer - Schrauder, M.; Frank, S.; Strissel, Pamela; Lux, Michael P.; Bani, Mayada; Rauh, C.; Sieber, Cornel; Heusinger, K.; Hartmann, Arndt; Schulz-Wendtland, Rüdiger; Strick, Reiner; Beckmann, Matthias; et al. (Journal of Cancer Research and Clinical Oncology, 2008)
Purpose Various ATM (ataxia telangiectasia-mutated) mutations and polymorphisms have been reported to be associated with an increased breast cancer risk. Recent studies have produced contradictory results regarding the association between ATM genetic variants and breast cancer risk.Materials and methods The common ATM polymorphism 5557G > A (p.D1853N) (rs1801516), previously suggested to be associated with bilateral breast cancer, was analyzed using real-time PCR in 514 unselected patients with breast cancer and 511 age-matched healthy control individuals. DNA was obtained from peripheral blood draw.Results The ATM genotype was weakly associated with the risk for breast cancer (P = 0.04 for the overall test). The odds ratio for women with a heterozygous genotype was 0.70 (95% CI, 0.52-0.94) and for the homozygous variant 0.63 (95% CI, 0.27-1.49). Disease-free survival and overall survival showed no significant association with specific genotypes.Conclusions The results of this study might suggest a minor association between polymorphism 5557G > A and a reduced risk of breast cancer.
Keywords: TM gene variants; polymorphism; breast cancer; DNA damage; epidemiology; association

Situation of Adolescent Contraceptive Use in Germany - Oppelt, Patricia; Fahlbusch, Christine; Heusinger, Katharina; Lotz, Laura; Dittrich, Ralf; Baier, Friederike (Geburtshilfe und Frauenheilkunde, 2018)
Introduction Would adolescent girls in Germany choose a different method of contraception to the combined oral contraceptive if provided with the appropriate information? Is there a need for long-acting contraception among our adolescent girls? How satisfied are female patients with the information they receive at their respective gynaecology practices, and how much do the girls know about different methods of contraception? Materials and Methods In the study "Thinking About Needs in COntraception" (TANCO), not only female patients, but also their respective gynaecologists were surveyed online about current methods of contraception, their satisfaction with these methods, and also their level of knowledge concerning the individual methods of contraception, the situation related to advice about different contraceptive options and their general satisfaction with gynaecological care. This article presents the data from the subset of adolescent girls aged 14 to 19 years (n = 2699) out of the total of 18 521 women surveyed. Results The girls surveyed were familiar with at least the name of more than five different methods of contraception (average 5.3). The doctors assumed that the respondents would know only 4.2 different methods. When asked explicitly about how the individual methods of contraception work, clear deficits became evident. This applies not only to the entire population of respondents, but also the users of the respective contraceptive method. In addition, a strong interest in long-acting contraception emerged from the survey, particularly among young women. Discussion The data from the TANCO study reveal a clear discrepancy between the existing contraception almost exclusively in the form of the contraceptive pill and the contraceptive options considered by adolescent girls if they are thoroughly informed. The need for education into alternatives to the pill is high, as is the willingness to use such alternatives after receiving information - much higher than the figures suggested by the gynaecologists.
EVALuna2:210080

Smartphone-Based Colorimetric Analysis of Urine Test Strips for At-Home Prenatal Care - Flaucher, Madeleine; Nissen, Michael; Jäger, Katharina; Titzmann, Adriana; Pontones, Constanza; Hübner, Hanna; Fasching, Peter; Beckmann, Matthias; Gradl, Stefan; Eskofier, Björn (IEEE Journal of Translational Engineering in Health and Medicine, 2022)
Objective: Clinical urine tests are a key component of prenatal care. As of now, urine test strips are evaluated through a time consuming, often error-prone and operator-dependent visual color comparison of test strips and reference cards by medical staff. Methods and procedures: This work presents an automated pipeline for urinalysis with urine test strips using smartphone camera images in home environments, combining several image processing and color combination techniques. Our approach is applicable to off-the-shelf test strips in home conditions with no additional hardware required. For development and evaluation of our pipeline we collected image data from two sources: i) A user study (26 participants, 150 images) and ii) a lab study (135 images). Results: We trained a region-based convolutional neural network that is able to detect the urine test strip location and orientation in images with a wide variety of light conditions, backgrounds and perspectives with an accuracy of 85.5%. The reference card can be robustly detected through a feature matching approach in 98.6% of the images. Color comparison by Hue channel (0.81 F1-Score), Matching factor (0.80 F1-Score) and Euclidean distance (0.70 F1-Score) were evaluated to determine the urinalysis results. Conclusion: We show that an automated smartphone-based colorimetric analysis of urine test strips in a home environment is feasible. It facilitates examinations and provides the possibility to shift care into an at-home environment. Clinical impact: The findings demonstrate that routine urine examinations can be transferred into the home environment using a smartphone. Simultaneously, human error is avoided, accuracy is increased and medical staff is relieve

Smart sensing in pregnancy: a survey-based evaluation of readiness to use wearable sensory applications in prenatal care - Weidenthaler, Filip; Danzberger, Nina; Pontones, Constanza; Titzmann, Adriana; Hein, Alexander; Beckmann, Matthias; Fasching, Peter; Huebner, H. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Sniper: A novel hypermethylation biomarker panel for liquid biopsy based early breast cancer detection - Mijnes, Jolein; Tiedemann, Janina; Eschenbruch, Julian; Gasthaus, Janina; Bringezu, Sarah; Bauerschlag, Dirk; Maass, Nicolai; Arnold, Norbert; Weimer, Jörg; Anzeneder, Tobias; Fasching, Peter; Rübner, Matthias; et al. (Oncotarget, 2019)
Introduction: Mammography is the gold standard for early breast cancer detection, but shows important limitations. Blood-based approaches on basis of cell-free DNA (cfDNA) provide minimally invasive screening tools to characterize epigenetic alterations of tumor suppressor genes and could serve as a liquid biopsy, complementing mammography. Methods: Potential biomarkers were identified from The Cancer Genome Atlas (TCGA), using HumanMethylation450-BeadChip data. Promoter methylation status was evaluated quantitatively by pyrosequencing in a serum test cohort (n = 103), a serum validation cohort (n = 368) and a plasma cohort (n = 125). Results: SPAG6, NKX2-6 and PER1 were identified as novel biomarker candidates. ITIH5 was included on basis of our previous work. In the serum test cohort, a panel of SPAG6 and ITIH5 showed 63% sensitivity for DCIS and 51% sensitivity for early invasive tumor (pT1, pN0) detection at 80% specificity. The serum validation cohort revealed 50% sensitivity for DCIS detection on basis of NKX2-6 and ITIH5. Furthermore, an inverse correlation between methylation frequency and cfDNA concentration was uncovered. Therefore, markers were tested in a plasma cohort, achieving a 64% sensitivity for breast cancer detection using SPAG6, PER1 and ITIH5. Conclusions: Although liquid biopsy remains challenging, a combination of SPAG6, NKX2-6, ITIH5 and PER1 (SNiPER) provides a promising tool for blood-based breast cancer detection.
CRIS-Team Scopus Importer:2019-12-03
Keywords: Breast cancer; Discriminative CpG dinucleotides; Early detection; Hypermethylation; Liquid biopsy

SNP-SNP interaction analysis of NF-?B signaling pathway on breast cancer survival - Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia; Aittomaki, Kristiina; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Andrulis, Irene L.; Chang-Claude, Jenny; Devilee, Peter; Fasching, Peter; Michailidou, Kyriaki; et al. (Oncotarget, 2015)
In breast cancer, constitutive activation of NF-?B has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-?B pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox' regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P=1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-?B pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses.
EVALuna2:17574

Socioeconomic status and depression during and after pregnancy in the Franconian Maternal Health Evaluation Studies (FRAMES) - Hein, Alexander; Rauh, Claudia; Engel, Anne; Häberle, Lothar; Dammer, Ulf; Voigt, Franziska; Fasching, Peter; Faschingbauer, Florian; Burger, Pascal; Beckmann, Matthias; Kornhuber, Johannes; Goecke, Tamme W. (Archives of Gynecology and Obstetrics, 2014)
Depression during and after pregnancy can have a negative impact on women's quality of life and on the development of the newborn child. Interventions have been shown to have a positive influence on both mothers and children. Predictive factors for depressive symptoms might possibly be able to identify groups that are at high risk. The aim of this study was to investigate the value of socioeconomic factors in predicting depressive symptoms during and after pregnancy.Depressiveness was measured using the German version of the 10-item Edinburgh Postnatal Depression Scale (EPDS) at three time-points, in a prospective cohort study (n = 1,100). Visit 1 (Q1) was at study entry in the third trimester of the pregnancy, visit 2 (Q2) was shortly after birth, and visit 3 (Q3) was 6-8 months after birth. Depression scores were associated with socioeconomic factors and time in linear mixed models.Parity status, education status, monthly income, residential property status, and partnership status, as well as interactions between them, were found to be predictive factors for EPDS scores. The strongest factor influencing depressive symptoms was partnership status. Women who did not have an intact partnership had EPDS scores that were on average four points higher than in women with a partner at all three study visits (P < 0.000001).Socioeconomic factors define subgroups that have different depression scores during and after pregnancy. Partnership status appears to be one of the most important influencing factors and could be useful for identifying women who should be offered an intervention to prevent possible negative effects on the mother or child.
EVALuna2:17434

Sonographic weight estimation in fetal macrosomia: influence of the time interval between estimation and delivery - Faschingbauer, Florian; Dammer, U.; Raabe, E.; Schneider, M.; Faschingbauer, Cornelia; Schmid, M.; Mayr, Andreas; Schild, R. L.; Beckmann, Matthias; Kehl, Sven (Archives of Gynecology and Obstetrics, 2015)
To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic weight estimation (WE) in fetal macrosomia.896 singleton pregnancies (birth weight > 4,000 g) with a total of 1,281 sonographic weight estimations were included in this retrospective cohort study. Fetuses were divided into six groups with regard to the time interval between estimation and delivery: group 1: scan-to-delivery interval: 0 days; group 2: scan-to-delivery interval: 1-3 days; group 3: scan-to-delivery interval: 4-7 days; group 4: scan-to-delivery interval: 8-14 days; group 5: scan-to-delivery interval: 15-21 days; group 6: scan-to-delivery interval: 22-42 days. The accuracy of WE was compared between five commonly used formulas using means of percentage errors (MPE), random error, medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight.Significant differences were found between the time interval groups with regard to MAPE and MPE values (p < 0.001). All formulas showed a systematic underestimation of fetal weight (negative MPEs) (p < 0.05). MPE values were closest to zero in time interval group 1 and 2. From group 3 to 6, a continuous decrease was observed. The lowest MAPE was found with the Merz formula in group 1 and 2. Values increased continuously from group 3 to 6. Differences between time interval group one and three did not reach statistical significance.WE in fetal macrosomia shows the best results when examinations are performed within 7 days before delivery, using the formula of Merz et al. Accuracy significantly decreases after this time period.
EVALuna2:5469

Sonographic Weight Estimation in Small-for-Gestational-Age Fetuses - Dammer, U.; Raabe, E.; Kehl, Sven; Schmid, M.; Mayr, Andreas; Schild, R. L.; Beckmann, Matthias; Faschingbauer, Florian (Ultraschall in der Medizin, 2015)
Purpose: To determine the accuracy of sonographic weight estimation (WE) for small-for-gestational-age (SGA) fetuses, and to further differentiate the evaluation between symmetric and asymmetric SGA fetuses. Materials and Methods: The accuracy of WE in SGA fetuses (n = 898) was evaluated using 14 sonographic models and was further differentiated between symmetric (n = 750) and asymmetric (n = 148) SGA fetuses. SGA fetuses were considered to be asymmetric with a head circumference to abdominal circumference ratio above the 95th percentile. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. Results: Results for the subgroup of asymmetric SGA fetuses differed significantly from the subgroup of symmetric SGA fetuses. MPE values were closer to zero with most of the formulas in the asymmetric SGA group. Apart from the Siemer, Shepard, Merz and Warsof equations, all formulas showed an underestimation of fetal weight in asymmetric SGA fetuses. In contrast, in the symmetric SGA group, all of the formulas commonly used for fetuses in a normal weight range showed a systematic overestimation of fetal weight. Overall the best accuracy was achieved by using the Sabbagha equation (MPE 1.7 %; SD 9.0 %; MAPE: 6.0). Conclusion: An accurate WE in SGA fetuses is feasible using the Sabbagha formula. However, one has to be aware of the significant differences in WE between symmetric and asymmetric SGA fetuses.
EVALuna2:5471

Sorafenib in combination with docetaxel as first-line therapy for HER2-negative metastatic breast cancer: Final results of the randomized, double-blind, placebo-controlled phase II MADONNA study - Mavratzas, A.; Baek, S.; Gerber, B.; Schmidt, Marcus; Moebus,; Foerster, F.; Grischke, E. M.; Fasching, Peter; Strumberg, D.; Solomayer, E.; Klare, P.; Windemuth-Kieselbach, C.; et al. (BREAST, 2019)
Background: This multicenter, double-blind phase II study assessed the antitumor activity and toxicity profile of docetaxel with the antiangiogenic multikinase inhibitor sorafenib or matching placebo as a first-line treatment in patients with metastatic or locally advanced HER2-negative breast cancer. Patients and methods: Patients were randomized 1:1 to receive docetaxel 100 mg/m 2 on day 1 every 3 weeks in combination with sorafenib 400 mg bid or placebo on days 2–18 of each cycle until tumor progression, or unacceptable toxicity. Sorafenib/placebo could be continued at the investigator's discretion if docetaxel was stopped due to toxicity. Primary endpoint was progression free survival (PFS). Results: From October 2008 to December 2013, 102 patients were randomized; 98 patients were evaluable. The trial was prematurely terminated due to slow accrual. Due to increased toxicity the dose of docetaxel was reduced to 75 mg/m 2 and an increasing sorafenib dosing schedule was implemented as part of a protocol amendment. The addition of sorafenib to docetaxel did not improve PFS (8.2 vs. 7.3 months for docetaxel/placebo; HR 0.84, log rank p = 0.43), but led to higher rates of early treatment discontinuation. There were no statistically significant differences between sorafenib dosing schedules. Conclusions: Addition of sorafenib to taxane-based first-line chemotherapy in patients with metastatic breast cancer failed to improve PFS and resulted in increased toxicity.
CRIS-Team Scopus Importer:2019-05-09
Keywords: Antiangiogenic agents; Docetaxel; Metastatic breast cancer; Sorafenib

Spatial expression of claudin 18.2 in matched primaries and metastases of tubo-ovarian carcinoma of all subtypes - Wagner, Paul; Gaß, Paul; Pöschke, Patrik; Eckstein, Markus; Gloßner, Laura; Hartmann, Arndt; Beckmann, Matthias; Fasching, Peter; Rübner, Matthias; Emons, Julius; Erber, Ramona (Virchows Archiv, 2024)
Physiologically, claudin 18 splice variant 2 (CLDN18.2) expression is restricted to the gastric epithelium, but its expression has been detected in solid cancers. Zolbetuximab, a chimeric IgG1 antibody targeting CLDN18.2, has demonstrated promising effects in patients suffering from CLDN18.2-positive, HER2-negative locally advanced gastric cancer and is currently being studied further. To date, little is known about CLDN18.2 expression in other histological subtypes of tubo-ovarian carcinoma (TOC) and their matching metastases. Using a cohort of all histological TOC subtypes, we investigated the immunohistochemical (IHC) CLDN18.2 expression in both TOCs (n = 536), their matching metastatic tissue (n = 385) and in 93 metastases without primary. Tissue microarrays comprised both the tumor center and periphery. IHC positivity was defined as biomarker expression of ≥ 75% in tumor cells with moderate-to-strong membranous staining. Overall CLDN18.2 positivity was 4.1% (21/515) in the TOC centers and 3.6% (18/498) in their peripheries. In primaries of mucinous tubo-ovarian carcinoma (MTOC), CLDN18.2 positivity rates were 45% (18/40) and 36.6% (15/41), respectively. Positivity rates for the corresponding metastases were 33% (4/12, center) and 27% (3/11, periphery). The expression was relatively homogenous throughout all tumor sites. With no expression in 99.5% of nonmucinous tumors, CLDN18.2 positivity was almost exclusively seen in the mucinous subtype. In tubo-ovarian carcinoma, CLDN18.2 expression was, with rare exceptions, restricted to the mucinous subtype. Among them, 33% of metastasized MTOCs presented with CLDN18.2 positivity. Hence, CLDN18.2 might display a promising target for personalized therapy in patients with advanced MTOC.
CRIS-Team Scopus Importer:2024-02-16
Keywords: CLDN18.2; Immunohistochemistry; Mucinous tubo-ovarian carcinoma; Targeted therapy; Tubo-ovarian cancer

Spatial Immunephenotypes of Distant Metastases but not Matched Primary Urothelial Carcinomas Predict Response to Immune Checkpoint Inhibition - Erlmeier, Franziska; Klümper, Niklas; Landgraf, Laura; Strissel, Pamela; Strick, Reiner; Sikic, Danijel; Taubert, Helge; Wach, Sven; Geppert, Carol-Immanuel; Bahlinger, Veronika; Breyer, Johannes; Ritter, Manuel; et al. (European Urology, 2022)
Background: The value of programmed cell death ligand-1 (PD-L1) to predict durable responses to immune checkpoint inhibitors (ICIs) in metastatic urothelial carcinoma (mUC) is inconsistent. We hypothesize that the use of archived primary tumor material (PRIM) for PD-L1 testing in clinical trials not properly reflecting the metastatic disease status (MET) contributes to this clinical issue. Objective: To analyze the predictive and prognostic value of PD-L1, spatial immunephenotypes, and major histocompatibility complex class I (MHC-I) determined in patient-matched PRIM/MET. Design, setting, and participants: PD-L1, spatial immunephenotypes, and MHC-I were examined in 154 mUC patients with at least one available pretreatment MET (138 patient-matched PRIM/MET pairs). Outcome measurements and statistical analysis: PD-L1, spatial immunephenotype, and MHC-I status of (patient-matched PRIM and) pretreatment MET were correlated with chemotherapy and ICI response and outcomes. Results and limitations: Discordance rates in patient-matched PRIM/MET were 25/30%, 36%, and 49% for PD-L1 (CPS10/IC5%), immunephenotypes, and MHC-I (loss vs preserved), respectively. Correlations with chemotherapy and ICI responses were observed for immunephenotypes and MHC-I status determined in MET (not for PD-L1 alone), but not in PRIM. In case of ICIs, patients with cytotoxic tumor immune microenvironment (TIME) showed durable responses with disease control rates of 90% and a hazard ratio for disease progression/death of 0.05 (95% confidence interval: 0.01–0.65) versus patients with immunedepleted MET (disease control rate 29%). MET MHC-I status added an incremental value to predict durable ICI responses. Limitations include the partly retrospective design and the lack of MET multisampling on individual patient level. Conclusions: The TIME is subject to substantial dynamics during metastatic evolution. MET immunephenotypes and MHC-I statuses show promising potential to predict chemotherapy and durable ICI responses, while the PRIM TIME does not. Thus, future clinical trials should rather rely on pretreatment MET biopsies reflecting the current immunological disease state than on PRIM. Patient summary: Prediction of chemotherapy and responses to immune checkpoint inhibitors might be possible using representative pretreatment metastatic biopsies.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Immune microenvironment; Immune therapy; Metastatic urothelial cancer; Subtypes; Urothelial cancer

Specific microRNA signatures in exosomes of triple-negative and HER2-positive breast cancer patients undergoing neoadjuvant therapy within the GeparSixto trial - Stevic, Ines; Mueller, Volkmar; Weber, Karsten; Fasching, Peter; Karn, Thomas; Marme, Frederic; Schem, Christian; Stickeler, Elmar; Denkert, Carsten; Van Mackelenbergh, Marion; Salat, Christoph; Schneeweiss, Andreas; et al. (BMC Medicine, 2018)
BACKGROUND: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). METHODS: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization. RESULTS: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR). CONCLUSION: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
EVALuna2:210019

Spectrum and Frequency of Germline FANCM Protein-Truncating Variants in 44,803 European Female Breast Cancer Cases - Figlioli, Gisella; Billaud, Amandine; Wang, Qin; Bolla, Manjeet K.; Dennis, Joe; Lush, Michael; Kvist, Anders; Adank, Muriel A.; Ahearn, Thomas U.; Antonenkova, Natalia N.; Auvinen, Päivi; Behrens, Sabine; et al. (Cancers, 2023)
FANCM germline protein truncating variants (PTVs) are moderate-risk factors for ER-negative breast cancer. We previously described the spectrum of FANCM PTVs in 114 European breast cancer cases. In the present, larger cohort, we report the spectrum and frequency of four common and 62 rare FANCM PTVs found in 274 carriers detected among 44,803 breast cancer cases. We confirmed that p.Gln1701* was the most common PTV in Northern Europe with lower frequencies in Southern Europe. In contrast, p.Gly1906Alafs*12 was the most common PTV in Southern Europe with decreasing frequencies in Central and Northern Europe. We verified that p.Arg658* was prevalent in Central Europe and had highest frequencies in Eastern Europe. We also confirmed that the fourth most common PTV, p.Gln498Thrfs*7, might be a founder variant from Lithuania. Based on the frequency distribution of the carriers of rare PTVs, we showed that the FANCM PTVs spectra in Southwestern and Central Europe were much more heterogeneous than those from Northeastern Europe. These findings will inform the development of more efficient FANCM genetic testing strategies for breast cancer cases from specific European populations.
CRIS-Team Scopus Importer:2023-07-28
Keywords: breast cancer predisposition; breast cancer risk factors; FANCM PTVs spectrum; protein truncating variants; PTVs

Sperm activating odorous substances in human follicular fluid and vaginal secretion: Identification by gas chromatography-olfactometry and Ca2+ imaging. - Hartmann, Constanze; Triller, Annika; Spehr, Marc; Dittrich, Ralf; Hatt, Hanns; Büttner, Andrea (ChemPlusChem, 2013)
Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography-olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor-ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α-androst-16-en-3-one and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, are shown.<br

Sperm activating odorous substances in human follicular fluid and vaginal secretion: Identification by gas-chromatography-olfactometry and CA2+-imaging - Hartmann, Constanze; Triller, Annika; Spehr, Marc; Dittrich, Ralf; Hatt, Hanns; Büttner, Andrea (ChemPlusChem, 2013)
Human sperm chemotaxis to follicular fluid has been well established, but the molecular mechanism(s) for this phenomenon are still largely unclear. Studies indicate that odorant receptors expressed on spermatozoa could play a role in this scenario. It has recently been shown that several synthetic floral scents activate the receptors OR1D2, OR4D1, and OR7A5 in vitro and evoke distinct sperm motility patterns in vivo. However, all agonists found so far are of synthetic origin and, thus, the presence of endogenous structural analogues in female bodily fluids is subject to speculation. Therefore, the aim of the study reported herein was to investigate the occurrence of odor compounds in vaginal secretions and follicular fluid by using gas chromatography- olfactometry. Chemically identified constituents of either bodily fluid were then analyzed for activation of recombinant chemoreceptors and candidate ligands were further tested for induction of sperm Ca2+ signals. Through using this approach, two novel odorant receptor-ligand pairs are reported and human sperm Ca2+ elevations in response to both odorous substances, namely 5α-androst-16-en-3-one and 4-hydroxy-2,5-dimethyl-3(2H)-furanone, are shown. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
UnivIS-Import:2015-04-14:Pub.2013.nat.dchph.llmch.sperma
Keywords: biological activity; calcium signaling; gas chromatography-olfactometry; membrane proteins; receptors

Spontaneous antral follicle formation and metaphase II oocyte from a non-stimulated prepubertal ovarian tissue xenotransplant - Lotz, Laura; Liebenthron, Jana; Nichols-Burns, Stephanie M.; Montag, Markus; Hoffmann, Inge; Beckmann, Matthias; Van Der Ven, Hans; Toepfer, Dagmar; Dittrich, Ralf (Reproductive Biology and Endocrinology, 2014)
Current strategies in cancer treatment have markedly increased the rates of remission and survival for cancer patients, but are often associated with subsequent sterility. While there are various options available to an adult female depending on the patient's particular situation, the only realistic option for preserving fertility in prepubertal females is to cryopreserve ovarian tissue. This is the first report of a morphologically mature oocyte collected from non-stimulated prepubertal ovarian tissue xenotransplants.Ovarian tissue from a 6 year old patient suffering from nephroblastoma was removed and cryopreserved for fertility preservation. The frozen-thawed ovarian tissue fragments were xenotransplanted to bilaterally oophorectomized severe combined immunodeficiency (SCID) mice to assess follicle development.Antral follicle formation occurred post-xenotransplantation in a single ovarian fragment without exogenous hormone stimulation. A morphologically maturing oocyte was harvested from these follicles.Prepubertal human ovarian follicles and oocytes can be matured after xenotransplantation even without exogenous hormone stimulation. These results indicate that tissue collected from prepubertal patients can support fertility in cancer survivors.
EVALuna2:17456

Stammzellen aus Nabelschnurblut - ein besonderes Gut: Informationen für eine fachärztliche Beratung der Schwangeren - Goecke, Tamme W.; Jud, Sebastian; Weisbach, Volker Günter; Bender, A. W.; Schneider, Holm (Geburtshilfe und Frauenheilkunde, 2010)
CRIS-Team Scopus Importer:2020-07-01

Standard changing news der Senologie und der Gynäkologischen Onkologie 2018 - Preu, Caroline; Heindl, Felix; Jud, Sebastian; Hein, Alexander; Hack, Carolin; Beckmann, Matthias; Lux, Michael P.; Rauh, Claudia (Klinikarzt, 2018)
CRIS-Team Scopus Importer:2021-07-19

Standard changing news der Senologie und der Gynäkologischen Onkologie 2019: Neue Arzneimittelzulassungen und Änderungen bestehender Therapiekonzepte - Preuβ, Caroline; Hein, Alexander; Beckmann, Matthias; Jud, Sebastian (Klinikarzt, 2019)
CRIS-Team Scopus Importer:2020-02-21

Standard Changing News der Senologie und der Gynäkologischen Onkologie 2020 - Preuβ, Caroline; Hein, Alexander; Beckmann, Matthias; Jud, Sebastian (Klinikarzt, 2020)
CRIS-Team Scopus Importer:2020-12-11

Standard Changing News der Senologie und Gynäkologischen Onkologie - Rauh, Claudia; Jud, Sebastian; Hein, Alexander; Hack, Carolin; Fasching, Peter; Beckmann, Matthias; Lux, Michael P. (Klinikarzt, 2017)
CRIS-Team Scopus Importer:2021-07-19

Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group - Denkert, Carsten; Wienert, Stephan; Poterie, Audrey; Loibl, Sibylle; Budczies, Jan; Badve, Sunil; Bago-Horvath, Zsuzsanna; Bane, Anita; Bedri, Shahinaz; Brock, Jane; Chmielik, Ewa; Christgen, Matthias; et al. (Modern Pathology, 2016)
Multiple independent studies have shown that tumor-infiltrating lymphocytes (TIL) are prognostic in breast cancer with potential relevance for response to immune-checkpoint inhibitor therapy. Although many groups are currently evaluating TIL, there is no standardized system for diagnostic applications. This study reports the results of two ring studies investigating TIL conducted by the International Working Group on Immuno-oncology Biomarkers. The study aim was to determine the intraclass correlation coefficient (ICC) for evaluation of TIL by different pathologists. A total of 120 slides were evaluated by a large group of pathologists with a web-based system in ring study 1 and a more advanced software-system in ring study 2 that included an integrated feedback with standardized reference images. The predefined aim for successful ring studies 1 and 2 was an ICC above 0.7 (lower limit of 95% confidence interval (CI)). In ring study 1 the prespecified endpoint was not reached (ICC: 0.70; 95% CI: 0.62-0.78). On the basis of an analysis of sources of variation, we developed a more advanced digital image evaluation system for ring study 2, which improved the ICC to 0.89 (95% CI: 0.85-0.92). The Fleiss' kappa value for <60 vs ≥60% TIL improved from 0.45 (ring study 1) to 0.63 in RS2 and the mean concordance improved from 88 to 92%. This large international standardization project shows that reproducible evaluation of TIL is feasible in breast cancer. This opens the way for standardized reporting of tumor immunological parameters in clinical studies and diagnostic practice. The software-guided image evaluation approach used in ring study 2 may be of value as a tool for evaluation of TIL in clinical trials and diagnostic practice. The experience gained from this approach might be applicable to the standardization of other diagnostic parameters in histopathology.
EVALuna2:33063

Standardized Procedures for Patients with Dysplasia and Other Diseases of the Cervix, Vulva, and Vagina at a Certified Dysplasia Unit Prior to the Introduction of the Organized Cervical Cancer Screening Program. - Schulmeyer, Carla; Koch, Martin C.; Dietl, Anna; Stübs, Frederik; Behrens, Annika; Renner, Simone K.; Mehlhorn, Grit; Geppert, Carol-Immanuel; Hartmann, Arndt; Beckmann, Matthias; Gaß, Paul (Geburtshilfe und Frauenheilkunde, 2023)
Introduction Gynecologic dysplasia units and dysplasia consultations are obliged to offer diagnosis and treatment in accordance with the guidelines. The organization of the consultation process, management of patient appointments, diagnosis, and treatment algorithms are heterogeneous. The legislation arising from the new Federal Joint Committee decision, dated 22 November 2018, concerning the organized cervical cancer screening program has been in force since 1 January 2020. In this article we provide an overview of the existing structures and interdisciplinary cooperation of specialized dysplasia units incorporated in certified gynecologic cancer center. Materials and Methods We carried out a retrospective database search of data collected prospectively from 1 July 2014 to 31 December 2019 at the dysplasia unit at the Department of Gynecology and Obstetrics, Erlangen University Hospital, which was the first dysplasia unit to be certified in 2014. Results A total of 5594 patients presented at the unit, and 16061 colposcopic, vulvoscopic, and anoscopic examinations were performed. Approximately 4100 examinations of the cervix, vagina, vulva, and anus are carried out each year, 1600 of these were exclusively cervix colposcopies. A total of 12197 cytology results were assessed, as well as 4850 histology results, and 8193 high-risk HPV tests. The quality indicators required by the dysplasia unit for annual recertification were met each year. Conclusion Certified dysplasia units and consultations form the central component in the algorithm for further investigating abnormal screening results; but they are also the first point of contact for a large number of patients with acute or chronic complaints in the genital region.
EVALuna2:542837

Standards Used by a Clinical and Scientific Endometriosis Center for the Diagnosis and Therapy of Patients with Endometriosis - Burghaus, Stefanie; Hildebrandt, Thomas; Fahlbusch, Christine; Heusinger, Katharina; Antoniadis, Sophia; Lermann, Johannes; Hackl, Janina; Häberle, Lothar; Renner, Stefan P.; Fasching, Peter; Beckmann, Matthias; Blum, Simon (Geburtshilfe und Frauenheilkunde, 2019)
Endometriosis is one of the most common benign gynecological diseases. The extremely heterogeneous complex of symptoms complicates the diagnosis and treatment of this disease. In most patients, there is a latency period of several years between the first occurrence of symptoms and the definitive diagnosis. This paper aims (1) to evaluate standards for the diagnosis and treatment of patients with (symptoms suspicious for) endometriosis in terms of feasibility, and (2) to assess the potential use of data collected by a certified clinical and scientific endometriosis center to answer scientific questions. Standards for outpatient consultations were developed for a special endometriosis outpatient clinic. Between January 2014 and December 2017, a total of 1715 outpatients with a suspicion of endometriosis presented to this special endometriosis outpatient clinic; the diagnosis and treatment of patients was carried out in accordance with the developed standards. Data of this patient cohort obtained from patient records created during outpatient consultations and from a questionnaire recorded in an Oracle-based database was analyzed. The patient cohort was also compared with another patient cohort who had attended different outpatient clinics and had been diagnosed intraoperatively with endometriosis. 41.8% of patients examined during special outpatient consultations had surgery for suspicion or recurrence of endometriosis. Endometriosis was confirmed in 81.5% of cases. Pain symptoms were the main indication for surgery in 70.1% of cases compared to 45.1% of cases in the comparison group. The structured approach used in the special endometriosis outpatient clinic is a key aspect of the care provided by the certified clinical and scientific endometriosis center. It ensures that patients are diagnosed and treated in accordance with guideline recommendations, that diagnosis and treatment comply with certification requirements, and that the collected data can be used to answer scientific questions.
CRIS-Team Scopus Importer:2019-06-04
Keywords: diagnostic; endometriosis; lower abdominal pain; sterility

Statement by the German Society for Gynecology and Obstetrics e.V. on the Topic - More Knowledge "Breast Density" - Seelbach-Goebel, Birgit; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2017)
EVALuna2:36148

Statement of the AGO and AG-CPC on the Aftercare/Follow-up for Surgical Procedures of the Lower Genital Tract after the Introduction of a New Cancer Screening Guideline - Hillemanns, Peter; Tempfer, Clemens; Beckmann, Matthias; Kueppers, Volkmar; Quaas, Jens (Geburtshilfe und Frauenheilkunde, 2020)
The new guideline on organized cancer screening programs has been in force in Germany since January 1st, 2020. The guideline has amended earlier recommendations on cytological examinations, which were previously carried out annually during screening. The guidelines-based recommendations on the appropriate follow-up for preinvasive and invasive lesions of the uterine cervix and endometrium are briefly outlined and differentiated from screening cytology and Pap/HPV co-testing as described in the guideline on organized cancer screening programs (oKFE-RL).
CRIS-Team WoS Importer:2020-09-11

Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on Surgical Therapy for Patients with Stage IA2-IIB1 Cervical Cancer - Fehm, Tanja; Beckmann, Matthias; Mahner, Sven; Denschlag, Dominik; Brucker, Sara; Hillemanns, Peter; Tempfer, Clemens (Geburtshilfe und Frauenheilkunde, 2023)
The presentation of the results of the prospective randomized international multicenter study AGO-OP.8 - CCTG CX.5 - SHAPE at the annual conference of the American Society of Clinical Oncology (ASCO) in 2023 will affect the surgical treatment of early-stage cervical cancer. In the SHAPE study, simple total hysterectomy (experimental arm) was found to be non-inferior to radical hysterectomy (standard arm) to treat patients with early-stage cervical cancer (FIGO stages [2018] IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm); after 3 years' follow-up the pelvic recurrence rate was 2.52% (experimental arm) compared to 2.17% (standard arm) with no statistically significant difference with regards to recurrence-free survival and overall survival rates. After weighing up the results of the SHAPE study published at the conference, the Uterus Organ Commission of AGO is of the opinion that, in addition to the use of radical hysterectomy to treat patients with invasive cervical cancer which is FIGO stage IA2 - IB1 ≤ 2 cm with an infiltration depth of < 1 cm, simple total hysterectomy may also be considered for primary surgical therapy on a case-by-case basis after suitable explanation of the associated risks. It will be necessary to wait for the data of the full publication before discussing whether this approach should be included in official guidelines and defining it as a new therapy standard.
CRIS-Team Scopus Importer:2023-10-27
Keywords: cervical cancer; early-stage; radical hysterectomy; simple hysterectomy