Influence of body mass index on induction of labor: A historical cohort study - Dammer, Ulf; Bogner, Roswitha; Weiss, Christel; Faschingbauer, Florian; Pretscher, Jutta; Beckmann, Matthias; Suetterlin, Marc; Kehl, Sven (Journal of Obstetrics and Gynaecology Research, 2018)
AIM: We aimed to determine the influence of body mass index (BMI) on induction of labor. METHODS: In this historical multicenter cohort study, 2122 labor inductions were analyzed. Women were divided into four groups according to their body mass index (BMI): BMI < 30 (normal group [NG]), 30 ≤ BMI < 35 (group 1 [G1]), 35 ≤ BMI < 40 (group 2 [G2]), and BMI ≥ 40 (group 3 [G3]). The primary outcome measure was the induction-to-delivery interval. The secondary outcome parameter was, among others, the rate of cesarean section. RESULTS: A total of 1113 inductions of labor were analyzed in the NG, 610 in G1, 239 in G2, and 160 in G3. The induction-to-delivery interval was shorter in the NG compared to G1 (mean values 1550 min vs 1669 min, P = 0.0406), G2 (1745 min, P = 0.0294), and G3 (1899 min, P = 0.0008). The cesarean section rate was significantly higher in G1-G3 (G1: 30.8%, P < 0.001; G2: 30.5%, P < 0.0067; G3: 42.5%, P < 0.0001) compared to the NG (21.8%). There were more vaginal deliveries within 48 h in the NG (84%) compared to G1-G3 (78%, P = 0.0186; 75%, P = 0.0049; 75%, P = 0.0329). However, these findings could mainly be seen in nulliparous women when stratifying for parity. Multivariable analysis showed that high BMI increased the induction-to-delivery interval whereas high parity, gestational age, and Bishop score decreased it. CONCLUSION: An increased body mass index has a negative impact on induction of labor at term, especially in nulliparous women.
EVALuna2:209950

Influence of CDK4/6 inhibitors on the peripheral immune response in hormone receptor-positive breast cancer - Peuker, C. A.; Yaghobramzi, S.; Grunert, C.; Keilholz, L.; Hennig, S.; Schaper, S.; Brucker, S.; Decker, T.; Fasching, Peter; Fehm, T.; Janni, W.; Kuemmel, S.; et al. (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-10-23

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy - Wunderle, Marius; Häberle, Lothar; Hein, Alexander; Jud, Sebastian; Lux, Michael P.; Hack, Carolin; Emons, Julius; Heindl, Felix; Nabieva, Naiba; Löhberg, Christian; Schulz-Wendtland, Rüdiger; Hartmann, Arndt; et al. (Breast Care, 2020)
Purpose: In breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2,in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study. Patients and Methods: Breast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS). Results: Of 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85-1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88-1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history. Conclusions: In this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.
CRIS-Team Scopus Importer:2020-07-24
Keywords: Breast cancer; Family history; Neoadjuvant chemotherapy; Ovarian cancer; Pathological complete response; Prognosis

Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity - Hübner, Hanna; Heussner, Kirsten; Rübner, Matthias; Schmid, Matthias; Nadal, Jennifer; Wölfle, Joachim; Hartner, Andrea; Menendez-Castro, Carlos; Rauh, Manfred; Beckmann, Matthias; Kehl, Sven; Fahlbusch, Fabian (Archives of Gynecology and Obstetrics, 2020)
Purpose: Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11β-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11β-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections. Methods: Using LC–MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples. Results: Cortisol–cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth. Conclusion: Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids.
CRIS-Team Scopus Importer:2020-09-11
Keywords: 11beta-hydroxysteroid dehydrogenase; CRH; LC–MS/MS; Mode of delivery; Placenta

Influence of mindfulness-based Stress Reduction on Patients with Endometriosis in a randomized Cohort Study - Antoniadis, Sophia; Burghaus, Stefanie; Becker, Karina; Beckmann, Matthias; Hack, Caroline (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Influence of Patient and Hospital Characteristics on the Performance of Direct Reconstruction after Mastectomy - Hartrampf, J.; Ansmann, L.; Wesselmann, S.; Beckmann, Matthias; Pfaff, H.; Kowalski, C. (Geburtshilfe und Frauenheilkunde, 2014)
Aim: International studies have shown that the performance of a direct (or immediate) reconstruction (DR) after mastectomy is associated with patient (e.g., socio-economic status, insurance status, age) and hospital (number of cases, teaching status) characteristics. The present article addresses the question if such relationships also exist in Germany. Material and Methods: The results of a nationwide questionnaire to the patients of certified breast cancer centres were coupled with the clinical features of the patients and the characteristics of the hospital. Predictors for receiving a DR (vs. delayed or no reconstruction) were estimated by means of a logistic multilevel model for a sample of 1165 patients from 105 certified locations. Results: Substantial differences between the treating hospitals were found (intraclass correlation coefficient null model: 0.195) which can in part be explained by the total model (total model: 0.169). Patients with the following features are more likely to receive a DR: younger age, private health insurance, secondary school leaving certificate (vs. primary school leaving certificate), lower stage and acquisition of more information about reconstruction. ASA and partnership status are not statistically significantly related with DR. DR is more likely to be performed in hospitals with higher caseload of patients with primary breast cancer. Teaching status, operations per surgeon and urbanity of the location are not related to receiving a DR. Conclusions: Non-clinical features of the patients and the primary case number are associated with the performance of a DR, this poses questions concerning reasons and the equality of health care.
EVALuna2:17452

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients - Nabieva, Naiba; Kellner, S.; Fehm, T.; Häberle, Lothar; De Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H. -C.; Guggenberger, M.; Warm, M.; Harbeck, N.; et al. (Annals of Oncology, 2018)
Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole.The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT.Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit).These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.
EVALuna2:51618

Influence of patient and tumor characteristics on therapy persistence with letrozole in postmenopausal women with advanced breast cancer: results of the prospective observational EvAluate-TM study - Wallwiener, Markus; Nabieva, Naiba; Feisst, Manuel; Fehm, Tanja; De Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; et al. (BMC Cancer, 2019)
BackgroundTreatment of postmenopausal, hormone receptor-positive metastatic breast cancer (MBC) patients varies despite clear therapy guidelines, favoring endocrine treatment (ET). Aim of this study was to analyze persistence of palliative aromatase inhibitor (AI) monotherapy in MBC patients.MethodsEvAluate-TM is a prospective, multicenter, noninterventional study to evaluate treatment with letrozole in postmenopausal women with hormone receptor-positive breast cancer. To assess therapy persistence, defined as the time from therapy start to the end of the therapy (TTEOT), two pre-specified study visits took place after 6 and 12months. Competing risk survival analyses were performed to identify patient and tumor characteristics that predict TTEOT.ResultsOut of 200 patients, 66 patients terminated treatment prematurely, 26 (13%) of them due to causes other than disease progression. Persistence rate for reasons other than progression at 12months was 77.7%. Persistence was lower in patients who reported any adverse event (AE) in the first 30days of ET (89.5% with no AE and 56% with AE). Furthermore, patients had a lower persistence if they reported compliance problems in the past before letrozole treatment.ConclusionsDespite suffering from a life-threatening disease, AEs of an AI will result in a relevant number of treatment terminations that are not related to progression. Some subgroups of patients have very low persistence rates. Especially with regard to novel endocrine combination therapies, these data imply that some groups of patients will need special attention to guide them through the therapy process.Trial registrationClinical Trials Number: CFEM345DDE19
CRIS-Team WoS Importer:2019-07-09

Influence of PIK3CA mutations on breast cancer proliferation, lymphocyte infiltration and clinical outcome: Pooled analysis of 484 patients from three prospective multicentre GBG trials - Jank, P.; Loibl, S.; Fasching, Peter; Karn, T.; Marme, F.; Mueller, V.; Schem, C.; Stickeler, E.; Lederer, B.; Denkert, C. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-08-13

Influence of Preeclampsia on Induction of Labor at Term: A Cohort Study - Pretscher, Jutta; Weiss, Christel; Dammer, Ulf; Stumpfe, Florian; Faschingbauer, Florian; Beckmann, Matthias; Kehl, Sven (In Vivo, 2020)
Background/Aim: Even though vaginal delivery is a feasible option in patients with preeclampsia, the cesarean section rate in those patients is high. The aim of this study was to evaluate the influence of preeclampsia on induction of labor at term. Patients and Methods: This historical cohort study analyzed inductions of labor in women at term having preeclampsia versus women who were induced due to other reasons. The primary outcome measure was the cesarean section rate. Results: The cesarean section rate was higher in the preeclampsia group for both nulliparous and multiparous women after induction of labor but failed to reach statistical significane. The induction-to-delivery interval was longer in nulliparous women and the rate of vaginal birth within 48 h was lower in the nulliparous patiens with preeclampsia. However, the impact of preeclampsia on the cesarean section rate was not significant in the multivariable analysis following adjustment for BMI and parity. Conclusion: Preeclampsia at term did not influence the cesarean section rate in nulliparous and parous women when labor was induced.
CRIS-Team WoS Importer:2020-05-22

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study - Nabieva, Naiba; Fehm, T.; Häberle, Lothar; De Waal, J.; Rezai, M.; Baier, B.; Baake, G.; Kolberg, H. -C.; Guggenberger, M.; Warm, M.; Harbeck, N.; Wuerstlein, R.; et al. (European Journal of Cancer, 2018)
Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment.Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses.Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84).These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration.CFEM345DDE19.
EVALuna2:51279

Influence of Sonographic Fetal Weight Estimation Inaccuracies in Macrosomia on Perinatal Outcome - Pretscher, Jutta; Kehl, Sven; Stelzl, Patrick; Stumpfe, Florian; Mayr, Andreas; Schmid, Matthias; Staerk, Christian; Schild, Ralf; Beckmann, Matthias; Faschingbauer, Florian (Ultraschall in der Medizin, 2020)
Objective To evaluate the influence of inaccurate sonographic fetal weight estimation in macrosomia on the mode of delivery and neonatal outcome (NO). Methods In 14633 pregnancies between 2002 and 2016, this retrospective study evaluated the association between sonographic fetal weight estimation, true birth weight (BW), mode of delivery (primary cesarean section [pCS], secondary cesarean section, vaginal delivery, and operative vaginal delivery rates) and NO parameters (5-min Apgar <7, pH <7.1, neonatal intensive care unit [NICU] admission, shoulder dystocia). Singleton pregnancies >37+0 weeks with ultrasound-estimated fetal weight (EFW) within 7 days before delivery were included. The study population was divided into four groups: Group 1 (false-negative): EFW <4000g/BW ≥4000g; Group 2 (true-positive): EFW ≥4000g/BW ≥4000g; Group 3 (false-positive): EFW ≥4000g/BW <4000g; and Group 4 (true-negative): EFW <4000g/BW <4000g. Results As expected, the highest secondary cesarean section (sCS) rate was found in Group 2 (true-positive) (30.62%), compared with only 17.68% in Group 4 (true-negative). The sCS rate in the false-positive Group 3 was significantly higher (28.48%) in comparison with the false-negative Group 1 (21.22%; OR 1.48; 95% CI, 1.16 to 1.89; P=0.002). In comparison with the true-negative Group 4, univariate analyses showed significantly higher rates for sCS in all other groups: Odds ratio (OR) 2.06 for Group 2 (95% CI, 1.74 to 2.42; P<0.001), 1.85 for Group 3 (95% CI, 1.54 to 2.22, P <0.001), and 1.25 for Group 1 (95% CI, 1.05 to 1.49; P <0.01). No significant differences were found for NO between Groups 1 and 3 for the parameters 5-min Apgar <7 (P=0.75), pH <7.1 (P=0.28), or NICU admission (P=0.54). However, there was a significantly higher chance for shoulder dystocia in Group 1 compared with Group 3 (OR 4.58; 95% CI, 1.34 to 24.30; P=0.008). Conclusion Sonographic EFW inaccuracies in fetal macrosomia appear to have a greater impact on the mode of delivery than birth weight itself. Underestimation of fetal weight may be associated with a higher probability of shoulder dystocia.
CRIS-Team Scopus Importer:2021-04-19
Keywords: cesarean section rate; fetal macrosomia; fetal weight estimation; perinatal outcome; sonography

Influence of sonographic fetal weight estimation in (suspected) fetal macrosomia on perinatal outcome - Pretscher, Jutta; Kehl, Sven; Stelzl, Patrick; Stumpfe, Florian; Mayr, A.; Schmid, M.; Staerk, C.; Schild, R. L.; Beckmann, Matthias; Faschingbauer, Florian (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Influence of the Family Anamnesis of Breast or Ovarian Cancer on the pathological Complete Remission and the Prognosis in Patients with Breast Cancer after neoadjuvant Chemotherapy - Gaß, Paul; Haberle, L.; Hein, Alexander; Jud, Sebastian; Lux, M. P.; Hack, Caroline; Emons, J.; Heindl, Felix; Nabieva, Naiba; Löhberg, Christian; Schulz-Wendtland, Rüdiger; Hartmann, Arndt; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Influence of Timing of Antenatal Corticosteroid Administration on Morbidity of Preterm Neonates - Morhart, Patrick; Gärtner, Janis; Weiss, Christel; Stumpfe, Florian; Dammer, Ulf; Faschingbauer, Florian; Fahlbusch, Fabian; Beckmann, Matthias; Kehl, Sven (In Vivo, 2022)
Background/Aim: We investigated the impact of the timing of antenatal corticosteroid (ACS) administration on the clinical outcome of preterm infants. Patients and Methods: Two hundred and fifty-five preterm infants between 28+0 and 34+0 weeks of gestation were retrospectively assigned to one of two groups: In the first group, ACS was given within 7 days before birth; the second group, did not receive ACS during that period. The primary outcome parameter was respiratory failure (defined by need for continuous positive airway pressure or mechanical ventilation) due to grade 1-4 respiratory distress syndrome (RDS). Secondary outcomes included the rates of intraventricular hemorrhage (IVH), periventricular leukomalacia, and necrotizing enterocolitis. Results: The rate of RDS was significantly higher in the no ACS group (40% vs. 62%, p=0.0009), especially of the more severe grades 24 (n=37 vs. n=48, p=0.0121). In addition, IVH (1% vs. 9%, p=0.0041) and neonatal infections (72% vs. 89%, p=0.0025) were significantly increased. Univariable and multivariable regression analyses showed a lower likelihood of RDS in the ACS group [odds ratio (OR)=0.295] in infants born closer to term (OR=0.907) and following preterm onset of labor (OR=0.495). Similarly, we observed a lower probability of IVH in the ACS group (OR=0.098), with a higher probability of occurrence of IVH in pre-eclampsia/HELLP syndrome (hemolysis, elevated liver enzyme levels, low platelet count) (OR=7.914). Conclusion: ACS treatment within the last 7 days before birth significantly reduced the risk of RDS and IVH in preterm. These data emphasize that the timing of ACS administration determines its success.
CRIS-Team WoS Importer:2022-07-15

Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer - Couch, Fergus J.; Hart, Steven N.; Sharma, Priyanka; Toland, Amanda Ewart; Wang, Xianshu; Miron, Penelope; Olson, Janet E.; Godwin, Andrew K.; Pankratz, V. Shane; Olswold, Curtis; Slettedahl, Seth; Hallberg, Emily; et al. (Journal of Clinical Oncology, 2015)
Recent advances in DNA sequencing have led to the development of breast cancer susceptibility gene panels for germline genetic testing of patients. We assessed the frequency of mutations in 17 predisposition genes, including BRCA1 and BRCA2, in a large cohort of patients with triple-negative breast cancer (TNBC) unselected for family history of breast or ovarian cancer to determine the utility of germline genetic testing for those with TNBC.Patients with TNBC (N = 1,824) unselected for family history of breast or ovarian cancer were recruited through 12 studies, and germline DNA was sequenced to identify mutations.Deleterious mutations were identified in 14.6% of all patients. Of these, 11.2% had mutations in the BRCA1 (8.5%) and BRCA2 (2.7%) genes. Deleterious mutations in 15 other predisposition genes were detected in 3.7% of patients, with the majority observed in genes involved in homologous recombination, including PALB2 (1.2%) and BARD1, RAD51D, RAD51C, and BRIP1 (0.3% to 0.5%). Patients with TNBC with mutations were diagnosed at an earlier age (P < .001) and had higher-grade tumors (P = .01) than those without mutations.Deleterious mutations in predisposition genes are present at high frequency in patients with TNBC unselected for family history of cancer. Mutation prevalence estimates suggest that patients with TNBC, regardless of age at diagnosis or family history of cancer, should be considered for germline genetic testing of BRCA1 and BRCA2. Although mutations in other predisposition genes are observed among patients with TNBC, better cancer risk estimates are needed before these mutations are used for clinical risk assessment in relatives.
EVALuna2:9246

Inherited variants affecting RNA editing may contribute to ovarian cancer susceptibility: results from a large-scale collaboration - Permuth, Jennifer B.; Reid, Brett; Earp, Madalene; Chen, Y. Ann; Monteiro, Alvaro N. A.; Chen, Zhihua; Chenevix-Trench, Georgia; Fasching, Peter; Beckmann, Matthias; Lambrechts, Diether; Vanderstichele, Adriaan; Van Niewenhuyse, Els; et al. (Oncotarget, 2016)
RNA editing in mammals is a form of post-transcriptional modification in which adenosine is converted to inosine by the adenosine deaminases acting on RNA (ADAR) family of enzymes. Based on evidence of altered ADAR expression in epithelial ovarian cancers (EOC), we hypothesized that single nucleotide polymorphisms (SNPs) in ADAR genes modify EOC susceptibility, potentially by altering ovarian tissue gene expression. Using directly genotyped and imputed data from 10,891 invasive EOC cases and 21,693 controls, we evaluated the associations of 5,303 SNPs in ADAD1, ADAR, ADAR2, ADAR3, and SND1. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), with adjustment for European ancestry. We conducted gene-level analyses using the Admixture Maximum Likelihood (AML) test and the Sequence-Kernel Association test for common and rare variants (SKAT-CR). Association analysis revealed top risk-associated SNP rs77027562 (OR (95% CI)= 1.39 (1.17-1.64), P=1.0x10-4) in ADAR3 and rs185455523 in SND1 (OR (95% CI)= 0.68 (0.56-0.83), P=2.0x10-4). When restricting to serous histology (n=6,500), the magnitude of association strengthened for rs185455523 (OR=0.60, P=1.0x10-4). Gene-level analyses revealed that variation in ADAR was associated (P<0.05) with EOC susceptibility, with PAML=0.022 and PSKAT-CR=0.020. Expression quantitative trait locus analysis in EOC tissue revealed significant associations (P<0.05) with ADAR expression for several SNPs in ADAR, including rs1127313 (G/A), a SNP in the 3' untranslated region. In summary, germline variation involving RNA editing genes may influence EOC susceptibility, warranting further investigation of inherited and acquired alterations affecting RNA editing.
EVALuna2:33315

Inherited variants in the inner centromere protein (INCENP) gene of the chromosomal passenger complex contribute to the susceptibility of ER-negative breast cancer - Kabisch, Maria; Bermejo, Justo Lorenzo; Duennebier, Thomas; Ying, Shibo; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Shah, Mitul; Perkins, Barbara J.; Czene, Kamila; Darabi, Hatef; et al. (Carcinogenesis, 2015)
The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encoding key CPC components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB, BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control studies of the Breast Cancer Association Consortium. Possible associations were investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon 7 of INCENP was associated with overall breast cancer risk [per A allele odds ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR 0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed based on 1000 Genomes. The SNPs rs1047739 in the 3' untranslated region and rs144045115 downstream of INCENP showed the strongest association signals for overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest that INCENP in the CPC pathway contributes to ER-negative breast cancer susceptibility in the European population. In spite of a modest contribution of CPC-inherited variants to the total burden of sporadic and familial breast cancer, their potential as novel targets for breast cancer treatment should be further investigated.
EVALuna2:9268

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses - Chiappinelli, Katherine B.; Strissel, Pamela; Desrichard, Alexis; Li, Huili; Henke, Christine; Akman, Benjamin; Hein, Alexander; Rote, Neal S.; Cope, Leslie M.; Snyder, Alexandra; Makarov, Vladimir; Buhu, Sadna; et al. (Cell, 2015)
We show that DNA methyltransferase inhibitors (DNMTis) upregulate immune signaling in cancer through the viral defense pathway. In ovarian cancer (OC), DNMTis trigger cytosolic sensing of double-stranded RNA (dsRNA) causing a type I interferon response and apoptosis. Knocking down dsRNA sensors TLR3 and MAVS reduces this response 2-fold and blocking interferon beta or its receptor abrogates it. Upregulation of hypermethylated endogenous retrovirus (ERV) genes accompanies the response and ERV overexpression activates the response. Basal levels of ERV and viral defense gene expression significantly correlate in primary OC and the latter signature separates primary samples for multiple tumor types from The Cancer Genome Atlas into low versus high expression groups. In melanoma patients treated with an immune checkpoint therapy, high viral defense signature expression in tumors significantly associates with durable clinical response and DNMTi treatment sensitizes to anti-CTLA4 therapy in a pre-clinical melanoma model.
EVALuna2:17550

Inhibition of adhesion, proliferation, and invasion of primary endometriosis and endometrial stromal and ovarian carcinoma cells by a nonhyaluronan adhesion barrier gel - Renner, Stefan; Strissel, Pamela; Beckmann, Matthias; Lermann, Johannes; Burghaus, Stefanie; Hackl, Janina; Fasching, Peter; Strick, Reiner (BioMed Research International, 2015)
Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences.
EVALuna2:17548

Initial clinical results with a fusion prototype for mammography and three-dimensional ultrasound with a standard mammography system and a standard ultrasound probe - Emons, Julius; Wunderle, Marius; Hartmann, Arndt; Radicke, Marcus; Rauh, Claudia; Uder, Michael; Gaß, Paul; Fasching, Peter; Langemann, Hanna; Beckmann, Matthias; Schulz-Wendtland, Rüdiger; Jud, Sebastian (Acta Radiologica, 2018)
BACKGROUND: Combinations *Equal contributors. of different imaging techniques in fusion devices appear to be associated with improvements in diagnostic assessment. PURPOSE: The aim of this study was to test the feasibility of using an automated standard three-dimensional (3D) ultrasound (US) device fused with standard mammography for the first time in breast cancer patients. MATERIAL AND METHODS: Digital mammograms and 3D automated US images were obtained in 23 patients with highly suspicious breast lesions. A recently developed fusion machine consisting of an ABVS 3D US transducer from an Acuson S2000 machine and a conventional Mammomat Inspiration device (both Siemens Healthcare GmbH, Erlangen, Germany) were used for the purpose. The feasibility of the examinations, imaging coverage, and patients' experience of the procedure were examined. RESULTS: In 15 out of 19 patients, the region of interest (ROI) with the tumor marked in the mammogram was visible on US. The examination was experienced positively by the patients, with no unexpected pain or injury. The examination was time-saving and well tolerated. CONCLUSION: In conclusion, we have shown initial clinical feasibility of an US/radiography fusion prototype with good localization and evaluation of the ROIs. The combined examination was well tolerated. The simultaneous evaluation with mammography and US imaging may be able to improve detection and reduce examiner-related variability.
EVALuna2:34810

Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive, HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany - Schneeweiss, Andreas; Ettl, Johannes; Lüftner, Diana; Beckmann, Matthias; Belleville, Erik; Fasching, Peter; Fehm, Tanja N.; Geberth, Matthias; Häberle, Lothar; Hadji, Peyman; Hartkopf, Andreas D.; Hielscher, Carsten; et al. (BREAST, 2020)
Purpose: Treatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor–positive, HER2-negative (HR + HER2–) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported. Methods: The PRAEGNANT registry was used to identify advanced HR + HER2– BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed. Results: CDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy. Conclusions: In clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET.
CRIS-Team Scopus Importer:2020-10-02
Keywords: Abemaciclib; Advanced breast cancer; CDK4/6; Chemotherapy; Endocrine therapy; Metastatic; Palbociclib; Ribociclib

Initial Treatment of Patients with Primary Breast Cancer: Evidence, Controversies, Consensus: Spectrum of Opinion of German Specialists at the 15th International St. Gallen Breast Cancer Conference (Vienna 2017) - Untch, Michael; Huober, Jens; Jackisch, Christian; Schneeweiss, Andreas; Brucker, Sara Y.; Dall, Peter; Denkert, Carsten; Fasching, Peter; Fehm, Tanja; Gerber, Bernd; Janni, Wolfgang; Kuehn, Thorsten; et al. (Geburtshilfe und Frauenheilkunde, 2017)
The St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer has been held regularly (every second year in the last six years) for more than 30 years. This year, the findings of the International St. Gallen Consensus Panel and their implications for clinical practice were again discussed by a German working group of leading breast cancer specialists. Five of the breast cancer specialists from Germany were also members of this year's St. Gallen panel. A comparison between the St. Gallen recommendations and the annually updated treatment guidelines of the Gynecologic Oncology Group (AGO 2017) and the S3-guideline agreed upon in 2017 is useful. The recommendations of the St. Gallen panel represent an international cross-section of opinions of experts from different countries and different disciplines, while the S3-guideline and AGO guidelines are evidence-based. The motto of this year's 15th St. Gallen Conference was "Escalating and De-Escalating". The rationale behind this concept was to promote more individualized treatment and thereby reduce overtreatment as well as undertreatment.
EVALuna2:36191

Insufficient Angiogenesis: Cause of Abnormally Thin Endometrium in Subfertile Patients? - Alfer, Joachim; Happel, Lars; Dittrich, Ralf; Beckmann, Matthias; Hartmann, Arndt; Gaumann, Andreas; Buck, Volker U.; Classen-Linke, Irmgard (Geburtshilfe und Frauenheilkunde, 2017)
This study investigated subfertile patients with abnormally thin endometrium after infertility treatment. As they had adequate serum concentrations of hormones, an endometrial factor for subfertility was suspected.To elucidate the cause of subfertility, endometrial biopsies were taken in each patient in the late proliferative and mid-secretory phases of one menstrual cycle. Endometrial biopsies from women with normal menstrual cycles and confirmed fertility who were undergoing hysterectomy for benign uterine disease were used as positive controls. The tissue samples were investigated for steroid hormone receptor expression and for the proliferation marker Ki-67. Immunohistochemistry was performed with antibodies against the marker molecules for endometrial receptivity - ? 3 integrin, VEGF, LIF, and CD56 (large granular lymphocytes, LGLs).The steroid hormone receptors for estrogen (E2) and progesterone (P) were expressed normally (at the first biopsy) and were down-regulated (at the second biopsy) within the cycle. Strikingly, all of the marker molecules investigated showed negative or weak and inadequate expression in the mid-secretory phase. Numbers of LGLs remained as low as in the proliferative phase. In contrast, fertile patients were found to express these marker molecules distinctly in the mid-secretory phase.It may be hypothesized that a severe deficiency of these angiogenesis-related marker molecules leads to defective development of the endometrium, which remains thin. Deficient angiogenetic development may thus provide an explanation for the endometrial factor that causes infertility. Further investigations will need to focus on identifying the regulating factors that act between steroid receptor activation and the expression of these marker molecules.
EVALuna2:6870

Integrated Analysis of PTEN and p4EBP1 Protein Expression as Predictors for pCR in HER2-Positive Breast Cancer - Loibl, Sibylle; Darb-Esfahani, Silvia; Huober, Jens; Klimowicz, Alexander; Furlanetto, Jenny; Lederer, Bianca; Hartmann, Arndt; Eidtmann, Holger; Pfitzner, Berit; Fasching, Peter; Tiemann, Katharina; Jackisch, Christian; et al. (Clinical Cancer Research, 2016)
The PI3K/AKT pathway and phosphatase and tensin homolog (PTEN) aberrations are common in breast cancer. We investigated the correlation between phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), PTEN, p4EBP1 (phosphorylated E4 binding protein 1), and pathologic complete response (pCR) in patients receiving neoadjuvant therapy.We retrospectively evaluated PIK3CA, PTEN, and p4EBP1 protein expression in centrally HER2-positive patients (n = 181) who received epirubicin cyclophosphamide/trastuzumab followed by docetaxel/trastuzumab alone or concomitant/followed by capecitabine within the GeparQuattro study. PTEN was assessed using the automated quantitative immunofluorescence analysis and was analyzed as a dichotomic variable. p4EBP1 was assessed by immunohistochemistry and used as a continuous and dichotomic variable.p4EBP1 was available from 137, PTEN from 108, and PIK3CA genotype from 83 patients. Overall, the pCR rate in PTEN-low tumors was 27.6%, and in PTEN-high tumors, it was 57.1% (P = 0.010). pCR rates were not statistically different between PIK3CA wild-type and mutant (35% vs. 22%) or p4EBP1 IRS <= 4 and IRS > 4 (39% vs. 33%). pCR rate was 57.1% (8/14) in PTEN-high/PIK3CA wild-type and decreased to 15.4% in PTEN-low/PIK3CA-mutant tumors (P = 0.023). In multivariable analysis adjusted for baseline parameters, PTEN independently predicted pCR in the following cohorts: overall [OR, 7.54; 95% confidence interval (CI), 2.03-28.06; P = 0.003], PIK3CA wild-type (OR, 23.81; 95% CI, 1.75-324.05; P = 0.017), p4EBP1 IRS > 4 (OR, 11.53; 95% CI, 1.84-72.24; P = 0.009), and hormone receptor-positive (OR, 40.91; 95% CI, 2.93-570.44; P = 0.006). p4EBP1 was independently predictive for pCR in PIK3CA wild-type tumors (OR, 0.14; 95% CI, 0.03-0.78; P = 0.025).The study showed the potential role of PIK3CA genotype, PTEN, and p4EBP in predicting pCR after anthracycline-taxane-based chemotherapy and anti-HER2 treatment. Clin Cancer Res; 22(11); 2675-83. ©2016 AACR.
EVALuna2:6794

Intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for neoadjuvant treatment of high-risk early breast cancer (GeparOcto—GBG 84): A randomised phase III trial - Schneeweiss, Andreas; Moebus, Volker; Tesch, Hans; Hanusch, Claus; Denkert, Carsten; Luebbe, Kristina; Huober, Jens; Klare, Peter; Kuemmel, Sherko; Untch, Michael; Kast, Karin; Jackisch, Christian; et al. (European Journal of Cancer, 2019)
Background: GeparOcto compared efficacy and safety of two chemotherapy regimens in high-risk early breast cancer (BC): sequential treatment with intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly treatment with paclitaxel plus non-pegylated liposomal doxorubicin (M, Myocet®) with additional carboplatin (PM(Cb)) in triple-negative BC (TNBC). Patients and methods: Patients with cT1c-cT4a-d and centrally assessed human epidermal growth factor receptor (HER)2-positive BC or TNBC were eligible, irrespective of nodal status, luminal B-like tumours only if pN+. Patients were randomised (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m 2 ) followed by P (225 mg/m 2 ) followed by C (2000 mg/m 2 ), each q2w for 3 cycles or weekly P (80 mg/m 2 ) plus M (20 mg/m 2 ) plus, in TNBC, Cb (area under curve (AUC) 1.5). HER2-positive BC patients additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Primary end-point was pathological complete response (pCR, ypT0/is ypN0), secondary end-points included other pCR definitions, pCR in stratified subpopulations, tolerability and compliance. This trial is registered with ClinicalTrials.gov number NCT02125344. Results: 945/961 randomised patients started treatment. The median age was 48 years; 7.6% had cT3-4, 46% cN+, 66% G3, 40% HER2-positive, 43% TNBC. pCR rate with iddEPC was 48.3%, with PM(Cb) 48.0%, respectively (PM(Cb) versus iddEPC odds ratio 0.99; 95% confidence interval 0.77–1.28, P = 0.979) with no significant differences observed in TNBC, HER2-positive, luminal B-like subtypes. 16.4% with iddEPC and 34.1% with PM(Cb) discontinued treatment (P < 0.001), mainly due to adverse events; two patients on PM(Cb) died. Conclusions: In high-risk early BC there is no difference in pCR rates following neoadjuvant treatment with iddEPC or weekly PM(Cb), respectively. iddEPC is one of the effective dose-dense regimens feasible in daily practice.
CRIS-Team Scopus Importer:2019-06-04
Keywords: Carboplatin; Dose-dense; High-risk early breast cancer; Neoadjuvant

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Number 032/034-OL, April 2018) - Part 2 with Recommendations on the Therapy and Follow-up of Endometrial Cancer, Palliative Care, Psycho-oncological/Psychosocial Care/Rehabilitation/Patient Information and Healthcare Facilities - Emons, Guenter; Steiner, Eric; Vordermark, Dirk; Uleer, Christoph; Bock, Nina; Paradies, Kerstin; Ortmann, Olaf; Aretz, Stefan; Mallmann, Peter; Kurzeder, Christian; Hagen, Volker; Van Oorschot, Birgitt; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose Using evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal extent of surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy if required. An evidence-based optimal use of different therapeutic modalities should improve the survival rates and quality of life of these patients. This S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources included reviews of evidence, which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one part of the guideline. Identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then subsequently modified during structured consensus conferences and/or additionally amended online using the DELPHI method, with consent between members achieved online. The guideline report is freely available online. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of endometrial cancer including precancers and early endometrial cancer as well as recommendations on palliative medicine, psycho-oncology, rehabilitation, patient information and healthcare facilities to treat endometrial cancer. The management of precancers of early endometrial precancerous conditions including fertility-preserving strategies is presented. The concept used for surgical primary therapy of endometrial cancer is described. Radiotherapy and adjuvant medical therapy to treat endometrial cancer and uterine carcinosarcomas are described. Recommendations are given for the follow-up care of endometrial cancer, recurrence and metastasis. Palliative medicine, psycho-oncology including psychosocial care, and patient information and rehabilitation are presented. Finally, the care algorithm and quality assurance steps for the diagnosis, therapy and follow-up of patients with endometrial cancer are outlined.
EVALuna2:36537

Interdisciplinary Diagnosis, Therapy and Follow-up of Patients with Endometrial Cancer. Guideline (S3-Level, AWMF Registry Nummer 032/034-OL, April 2018) - Part 1 with Recommendations on the Epidemiology, Screening, Diagnosis and Hereditary Factors of Endometrial Cancer - Emons, Guenter; Steiner, Eric; Vordermark, Dirk; Uleer, Christoph; Bock, Nina; Paradiess, Kerstin; Ortmann, Olaf; Aretz, Stefan; Mallmann, Peter; Kurzeder, Christian; Hagen, Volker; Van Oorschot, Birgitt; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Summary The first German interdisciplinary S3-guideline on the diagnosis, therapy and follow-up of patients with endometrial cancer was published in April 2018. Funded by German Cancer Aid as part of an Oncology Guidelines Program, the lead coordinators of the guideline were the German Society of Gynecology and Obstetrics (DGGG) and the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG). Purpose The use of evidence-based, risk-adapted therapy to treat low-risk women with endometrial cancer avoids unnecessarily radical surgery and non-useful adjuvant radiotherapy and/or chemotherapy. This can significantly reduce therapy-induced morbidity and improve the patient's quality of life as well as avoiding unnecessary costs. For women with endometrial cancer and a high risk of recurrence, the guideline defines the optimal surgical radicality together with the appropriate chemotherapy and/or adjuvant radiotherapy where required. The evidence-based optimal use of different therapeutic modalities should improve survival rates and the quality of life of these patients. The S3-guideline on endometrial cancer is intended as a basis for certified gynecological cancer centers. The aim is that the quality indicators established in this guideline will be incorporated in the certification processes of these centers. Methods The guideline was compiled in accordance with the requirements for S3-level guidelines. This includes, in the first instance, the adaptation of source guidelines selected using the DELBI instrument for appraising guidelines. Other consulted sources include reviews of evidence which were compiled from literature selected during systematic searches of literature databases using the PICO scheme. In addition, an external biostatistics institute was commissioned to carry out a systematic search and assessment of the literature for one area of the guideline. The identified materials were used by the interdisciplinary working groups to develop suggestions for Recommendations and Statements, which were then modified during structured consensus conferences and/or additionally amended online using the DELPHI method with consent being reached online. The guideline report is freely available online. Recommendations Part 1 of this short version of the guideline presents recommendations on epidemiology, screening, diagnosis and hereditary factors, The epidemiology of endometrial cancer and the risk factors for developing endomentrial cancer are presented. The options for screening and the methods used to diagnose endometrial cancer including the pathology of the cancer are outlined. Recommendations are given for the prevention, diagnosis, and therapy of hereditary forms of endometrial cancer.
EVALuna2:36539

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 1 with Recommendations for the Screening, Diagnosis and Therapy of Breast Cancer - Woeckel, Achim; Festl, Jasmin; Stueber, Tanja; Brust, Katharina; Stangl, Stephanie; Heuschmann, Peter U.; Albert, Ute-Susann; Budach, Wilfried; Follmann, Markus; Janni, Wolfgang; Kopp, Ina; Kreienberg, Rolf; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure. Recommendations Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
EVALuna2:36235

Interdisciplinary Screening, Diagnosis, Therapy and Follow-up of Breast Cancer. Guideline of the DGGG and the DKG (S3-Level, AWMF Registry Number 032/045OL, December 2017) - Part 2 with Recommendations for the Therapy of Primary, Recurrent and Advanced Breast Cancer - Woeckel, Achim; Festl, Jasmin; Stueber, Tanja; Brust, Katharina; Krockenberger, Mathias; Heuschmann, Peter U.; Jiru-Hillmann, Steffi; Albert, Ute-Susann; Budach, Wilfried; Follmann, Markus; Janni, Wolfgang; Kopp, Ina; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of identified source guidelines. They were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and with the results of a systematic search of literature databases followed by the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point and used them to develop suggestions for recommendations and statements, which were then modified and graded in a structured consensus process procedure. Recommendations Part 2 of this short version of the guideline presents recommendations for the therapy of primary, recurrent and metastatic breast cancer. Loco-regional therapies are de-escalated in the current guideline. In addition to reducing the safety margins for surgical procedures, the guideline also recommends reducing the radicality of axillary surgery. The choice and extent of systemic therapy depends on the respective tumor biology. New substances are becoming available, particularly to treat metastatic breast cancer.
EVALuna2:36231

Interdisciplinary Treatment for Cutaneous Abdominal Wall Metastasis from Cervical Cancer with Resection and Reconstruction of the Abdominal Wall Using Free Latissimus Dorsi Muscle Flap: A Case Report - Boos, Anja; Beckmann, Matthias; Horch, Raymund E.; Beier, Justus (Geburtshilfe und Frauenheilkunde, 2014)
EVALuna2:15567

Interest in Integrative Medicine Among Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study - Hack, Carolin; Fasching, Peter; Fehm, Tanja; De Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; et al. (Integrative Cancer Therapies, 2017)
BACKGROUND: Breast cancer patients often use complementary and alternative medicine, but few prospectively collected data on the topic are available specifically for postmenopausal breast cancer patients. A large prospective study was therefore conducted within a noninterventional study in order to identify the characteristics of patients interested in integrative medicine. METHODS: The EvAluate-TM study is a prospective, multicenter noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive primary breast cancer. Between 2008 and 2009, 5045 postmenopausal patients were enrolled at 339 certified breast centers in Germany. As part of the data collection process, patients were asked at the baseline about their interest in and information needs relating to integrative medicine. RESULTS: Of the 5045 patients recruited, 3411 responded to the questionnaire on integrative medicine and took part in the analysis, 1583 patients expressed an interest in integrative medicine, and 1828 patients declared no interest. Relevant predictors of interest in integrative medicine were age, body mass index, tumor size, previous chemotherapy, and use of concomitant medications for other medical conditions. Interest in integrative medicine declined highly significantly ( P < .001) with age (<50 years, 74.1%; 50-60 years, 54.1%; >65 years, 38.0%). Patients in favor of integrative medicine were significantly less satisfied with the information received about individual treatments and antihormonal therapy. Patients with interest in integrative medicine were more often interested in rehabilitation and fitness, nutritional counseling, and additional support from self-help organizations. These women were mostly interested in receiving information about their disease and integrative medicine from a physician, rather than from other sources. CONCLUSIONS: This study shows that a considerable proportion of postmenopausal breast cancer patients are interested in integrative medicine. Information about integrative medicine should therefore be provided as part of patient care for this group. It was found that receiving concomitant medication for other medical conditions is one of the main predictors for women not being interested in integrative medicine. This group of patients may need special attention and individualized information about integrative medicine. Additionally, most patients were interested in obtaining the relevant information from their doctor.
EVALuna2:36142

Intermediate biopsies during neoadjuvant chemotherapy for breast cancer to predict patient outcome - Sinn, B. V.; Untch, M.; Karn, T.; Van Mackelenbergh, M.; Huober, J.; Sychra, K.; Schmitt, W. D.; Marme, F.; Schem, C.; Solbach, C.; Stickeler, E.; Tesch, H.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus - Assessment by a German Group of Experts - Thomssen, Christoph; Lüftner, Diana; Untch, Michael; Haidinger, Renate; Würstlein, Rachel; Harbeck, Nadia; Augustin, Doris; Briest, Susanne; Ettl, Johannes; Fasching, Peter; Förster, Frank; Kurbacher, Christian M.; et al. (Breast Care, 2020)
The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14-16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.
CRIS-Team Scopus Importer:2020-02-25

Intra- and Postoperative Blood Flow Monitoring in a Sheep Model of Uterus Transplantation - Kengelbach-Weigand, Annika; Lotz, Laura; Schmid, Rafael; Lang, Werner; Beckmann, Matthias; Hoffmann, Inge; Horch, Raymund E.; Renner, Stefan; Dittrich, Ralf; Boos, Anja; Hildebrandt, Thomas (In Vivo, 2019)
Background: The introduction of the opportunity to transplant a viable uterus into women for fulfilling their desire to have a child has awakened high expectations worldwide. Materials and Methods: A sheep model was used to evaluate tools for optimizing measurement of blood flow in uterine transplantation. Intraoperatively, blood flow was measured using unidirectional Doppler and indocyanine green (ICG) fluorescence imaging. Postoperatively, an implantable Doppler probe served as a tool for clinical monitoring the patency of anastomosed vessels. Results: ICG imaging showed complete vascularization of the uterus before and in short-term evaluation after surgery. The implantable Doppler probe proved to be highly suitable for assessing patency of vessels in a non-invasive way. Results of histology, and real-time polymerase chain reaction demonstrated viability of the transplanted uterus. Conclusion: Different methods to monitor vasculature patency have proven to be advantageous in supporting both surgeons and researchers in ensuring successful implementation of uterine transplantation.
CRIS-Team WoS Importer:2019-03-08

Intrapartum sonographic weight estimation - Faschingbauer, Florian; Dammer, U.; Raabe, E.; Schneider, M.; Faschingbauer, Cornelia; Schmid, M.; Schild, R. L.; Beckmann, Matthias; Kehl, Sven; Mayr, Andreas (Archives of Gynecology and Obstetrics, 2015)
To evaluate the accuracy of intrapartum sonographic weight estimation (WE).This retrospective, cross-sectional study included 1958 singleton pregnancies. Inclusion criteria were singleton pregnancy with cephalic presentation, vaginal delivery and ultrasound examination with complete biometric parameters performed on the day of delivery during the latent or active phase of labor, and absence of chromosomal or structural anomalies. The accuracy of intrapartum WE was compared to a control group of fetuses delivered by primary cesarean section at our perinatal center and an ultrasound examination with complete biometric parameters performed within 3 days before delivery (n = 392). Otherwise, the same inclusion criteria as in the study group were applied. The accuracy of WE was compared between five commonly applied formulas using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight.In the whole study group, all equations showed a systematic underestimation of fetal weight (negative MPEs). Overall, best MAPE and MPE values were found with the Hadlock II formula, using BPD, AC and FL as biometric parameters (Hadlock II, MPE: -1.28; MAPE: 6.52). MPEs differed significantly between WE in the study and control group for all evaluated formulas: in the control group, either no systematic error (Hadlock III, IV and V) or a significant overestimation (Hadlock I, II) was found. Regarding MAPEs, application of the Hadlock III (HC, AC, FL) and V (AC) formula resulted in significant lower values in the control group (Hadlock III, MAPE: 7.48 vs. 5.95, p = 0.0008 and Hadlock V, MAPE: 8.79 vs. 7.52, p = 0.0085). No significant differences were found for the other equations.A systematic underestimation of fetal weight has to be taken into account in sonographic WE performed intrapartum. Overall, the best results can be achieved with WE formulas using the BPD as the only head measurement.
EVALuna2:5506

Intrauterine Growth Restriction (IUGR) Induces Signs of Subclinical Atherosclerosis in 6-Year-Old Infants Despite Absence Of Excessive Growth - Tzschoppe, Anja; Von Kries, Ruediger; Struwe, Ellen; Rascher, Wolfgang; Dörr, Helmuth-Günther; Juengert, Joerg; Rauh, Manfred; Beckmann, Matthias; Schild, Ralf; Goecke, Tamme W.; Doetsch, Joerg (Klinische Pädiatrie, 2017)
Background Postnatal catch-up growth and rapid weight gain after intrauterine growth restriction (IUGR) seem to increase the risk for later disease. This study aimed to compare features of the metabolic syndrome early in life between IUGR and appropriate for gestational age (AGA) infants. Patients Data for 9 infants with IUGR defined by a birth weight<10th percentile and ultrasound-proven placental insufficiency and 11 AGA children were available. Method Postnatal growth, auxological, cardiovascular, and metabolic parameters up to a chronological age of 6 years were assessed: Fasting serum concentrations of LDL-cholesterol, insulin, leptin, IGF-I, DHEAS, skinfold thicknesses, blood pressure, and mean carotid intima-media thickness (cIMT). Results All IUGR infants showed catch-up growth, although mean BMI SDS and total subcutaneous fat mass at the age of 6 years were still slightly lower compared to the AGA cohort. Reduced serum leptin concentrations were observed in IUGR infants (p=0.02), whereas no significant difference was found for IGF-I, insulin, LDL-cholesterol and DHEAS concentrations. Mean cIMT was significantly higher in IUGR infants (p<0.05). Mean arterial pressure did no differ. Discussion and Conclusion In 6-year-old IUGR infants with catch-up growth, who still had a slightly reduced BMI SDS compared to the AGA group, signs of subclinical atherosclerosis were detectable suggesting that cardiovascular risk in IUGR may be present even in the absence of excessive growth.
EVALuna2:34095

Introducing a novel highly prognostic grading scheme based on tumour budding and cell nest size for squamous cell carcinoma of the uterine cervix - Jesinghaus, Moritz; Strehl, Johanna; Boxberg, Melanie; Bruehl, Frido; Wenzel, Adrian; Konukiewitz, Bjoern; Schlitter, Anna M.; Steiger, Katja; Warth, Arne; Schnelzer, Andreas; Kiechle, Marion; Beckmann, Matthias; et al. (Journal of Pathology: Clinical Research, 2018)
A novel histopathological grading system based on tumour budding and cell nest size has recently been shown to outperform conventional (WHO-based) grading algorithms in several tumour entities such as lung, oral, and oesophageal squamous cell carcinoma (SCC) in terms of prognostic patient stratification. Here, we tested the prognostic value of this innovative grading approach in two completely independent cohorts of SCC of the uterine cervix. To improve morphology-based grading, we investigated tumour budding activity and cell nest size as well as several other histomorphological factors (e.g., keratinization, nuclear size, mitotic activity) in a test cohort (n = 125) and an independent validation cohort (n = 122) of cervical SCC. All parameters were correlated with clinicopathological factors and patient outcome. Small cell nest size and high tumour budding activity were strongly associated with a dismal patient prognosis (p < 0.001 for overall survival [OS], disease-specific survival, and disease-free survival; test cohort) in both cohorts of cervical SCC. A novel grading algorithm combining these two parameters proved to be a highly effective, stage-independent prognosticator in both cohorts (OS: p < 0.001, test cohort; p = 0.001, validation cohort). In the test cohort, multivariate statistical analysis of the novel grade revealed that the hazard ratio (HR) for OS was 2.3 for G2 and 5.1 for G3 tumours compared to G1 neoplasms (p = 0.010). In the validation cohort, HR for OS was 3.0 for G2 and 7.2 for G3 tumours (p = 0.012). In conclusion, our novel grading algorithm incorporating cell nest size and tumour budding allows strongly prognostic histopathological grading of cervical SCC superior to WHO-based grading. Therefore, our data can be regarded as a cross-organ validation of previous results demonstrated for oesophageal, lung, and oral SCC. We suggest this grading algorithm as an additional morphology-based parameter for the routine diagnostic assessment of this tumour entity.
EVALuna2:35627

Introducing multiple-choice questions to promote learning for medical students: effect on exam performance in obstetrics and gynecology - Jud, Sebastian; Cupisti, Susanne; Frobenius, Wolfgang; Winkler, Andrea; Schultheis, Franziska; Antoniadis, Sophia; Beckmann, Matthias; Heindl, Felix (Archives of Gynecology and Obstetrics, 2020)
Purpose: Testing is required in medical education. The large number of exams that students face requires effective learning strategies. Various methods of improving knowledge retention and recall have been discussed, two of the most widely evaluated of which are test-enhanced learning and pause procedures. This study investigated the effect of voluntary multiple-choice questions on students’ performance. Methods: In a prospective study from April 2013 to March 2015, 721 students were randomly assigned to receive supplementary online material only (control group) or additional multiple-choice questions (investigative group) accompanying lectures. Their performance in the final exam was evaluated. Results: A total of 675 students were ultimately included, with 299 randomly assigned to the investigative group and 376 to the control group. Students in the investigative group scored significantly better in relation to grades and points (2.11 vs. 2.49; 33 vs 31.31; p < 0.05). The effect declined over time. Conclusion: This is the first study of the use of voluntary multiple-choice questions to improve medical students’ performance. The results support test-enhanced learning and the feasibility of implementing multiple-choice questions in lectures.
CRIS-Team Scopus Importer:2020-09-18
Keywords: Gynecology; Lecture; Multiple choice; Obstetrics; Teaching; Testing

Introduction of Inhaled Nitrous Oxide and Oxygen for Pain Management during Labour - Evaluation of Patients' and Midwives' Satisfaction - Dammer, U.; Weiss, C.; Raabe, E.; Heimrich, J.; Koch, Matthias; Winkler, Michael; Faschingbauer, F.; Beckmann, Matthias; Kehl, Sven (Geburtshilfe und Frauenheilkunde, 2014)
Aim: Effective pain management during labour is important because pain affects the birth experience. Epidural analgesia is effective but often it may not be possible; however, inhaled analgesia offers another option. Use of inhaled nitrous oxide and oxygen for pain management in labour is well established in obstetrics but is still not used much in Germany. This study aimed to investigate the acceptance of the inhaled analgesia of inhaled nitrous oxide and oxygen by midwives and pregnant women during labour. Material and Methods: In this observational study carried out between April and September 2013, a total of 66 pregnant women received inhaled nitrous oxide and oxygen during labour on request and after prior assessment of suitability. After the birth, all of the women and the responsible midwives were interviewed about their experience and satisfaction with the inhaled analgesia. Results: A statistically significant reduction of pain was achieved with nitrous oxide and oxygen. The inhaled analgesia was mostly used by women who refused epidural analgesia. The likelihood of using inhaled nitrous oxide and oxygen again was reported as higher for patients who tolerated it well (p = 0.0129) and used it in the second stage of labour (p = 0.0003) and when bearing down (p = 0.0008). Conclusion: Inhaled nitrous oxide and oxygen is an effective method for pain management during labour and is accepted well by women in labour and by midwives.
EVALuna2:17457

Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors - Rudolph, Anja; Milne, Roger L.; Truong, Therese; Knight, Julia A.; Seibold, Petra; Flesch-Janys, Dieter; Behrens, Sabine; Eilber, Ursula; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Dunning, Alison M.; et al. (International Journal of Cancer, 2015)
A large genotyping project within the Breast Cancer Association Consortium (BCAC) recently identified 41 associations between single nucleotide polymorphisms (SNPs) and overall breast cancer (BC) risk. We investigated whether the effects of these 41 SNPs, as well as six SNPs associated with estrogen receptor (ER) negative BC risk are modified by 13 environmental risk factors for BC. Data from 22 studies participating in BCAC were pooled, comprising up to 26,633 cases and 30,119 controls. Interactions between SNPs and environmental factors were evaluated using an empirical Bayes-type shrinkage estimator. Six SNPs showed interactions with associated p-values (pint ) <1.1 × 10(-3) . None of the observed interactions was significant after accounting for multiple testing. The Bayesian False Discovery Probability was used to rank the findings, which indicated three interactions as being noteworthy at 1% prior probability of interaction. SNP rs6828523 was associated with increased ER-negative BC risk in women >=170 cm (OR = 1.22, p = 0.017), but inversely associated with ER-negative BC risk in women <160 cm (OR = 0.83, p = 0.039, pint = 1.9 × 10(-4) ). The inverse association between rs4808801 and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies.
EVALuna2:9245

Is ovarian tissue transport at supra-zero temperatures compared to body temperature optimal for follicle survival? - Raffel, Nathalie; Dittrich, Ralf; Orlowski, Paul; Tischer, Hannah; Sӧder, Stephan; Erber, Ramona; Hoffmann, Inge; Beckmann, Matthias; Lotz, Laura (In Vivo, 2020)
Background/Aim: Transportation of ovarian cortex prior to freezing is used clinically; however, basic investigations of ovarian storage are limited and the question remains what temperature is optimal for transport over long distances and time periods. The aim of this study was to evaluate the rate of follicular loss over various time periods under two different temperatures and assess whether ovarian follicle viability is affected following cryopreservation and thawing subsequent to the transportation of ovarian tissue. Materials and Methods: Pig ovaries were transported at 4oC (n=10) or at 38oC (n=10) prior to cryopreservation. At 0, 4, 12 and 24 h tissues were fixed for histological examination and a LIVE/DEAD Assay. At the same time-points ovarian tissues were cryopreserved and analysed after thawing. Results: Histological evaluation and LIVE/DEAD Assay of freshly transported ovarian tissue showed significantly better follicle survival at 4oC during transportation duration. In cryopreserved ovarian tissues the LIVE/DEAD Assay showed a significant difference in the number of intact and dead follicles at 24 h in favor of 4oC (p<0.05). Conclusion: Ovarian tissue transportation should be kept at a minimum to prevent potential damage.
CRIS-Team Scopus Importer:2020-03-17
Keywords: Cryopreservation; Fertility preservation; Follicle loss; Ovarian follicle viability; Ovarian storage; Ovarian tissue transportation

Is Reduction Mammoplasty Cost-Effective? A Cost-Utility Analysis of Surgical Treatment for Macromastia in Germany - Lux, Michael P.; Brendle-Behnisch, Anne; Hack, Carolin; Preuss, Caroline; Arkudas, Andreas; Horch, Raymund E.; Beckmann, Matthias; Jud, Sebastian (Breast Care, 2021)
Background/Aims: Macromastia can cause physical and psychological problems. Conservative treatments such as physiotherapy and painkillers lead to substantial long-term costs, without any proven medical benefit. In contrast, surgical treatment with reduction mammoplasty leads to improvements in nearly all respects. This study analyzed the costs of reduction mammoplasty and calculated an incremental cost-utility ratio for the treatment. Patients and Methods: The data on 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative) as well as the patients' files. Topics examined besides demographic data included physician visits, medical imaging, integrative medical procedures, remedial procedures, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before and after surgery. The data were used to calculate costs per year after surgical treatment for symptomatic macromastia. Costs of surgery, including the process of obtaining insurance reimbursement and postoperative complications, were taken into account to calculate the one-time costs of reduction mammoplasty. Results: The patients' quality of life and satisfaction with the breasts improve after surgery. The one-time costs of reduction mammoplasty per patient amount to EUR 5,885, and the annual costs after surgery are EUR 200. The incremental cost-utility ratio for surgical treatments shows a saving of EUR 380 per quality-adjusted life-year (QALY) gained. Conclusions: These results show that reduction mammoplasty is a treatment that not only improves a patient's quality of life but also saves money in the longer term in comparison with expensive and ineffective conservative treatment for macromastia.
CRIS-Team WoS Importer:2021-02-19

Is there a benefit of lymphadenectomy for overall and recurrence-free survival in type I FIGO IB G1-2 endometrial carcinoma? A retrospective population-based cohort analysis - Papathemelis, Thomas; Hassas, Dunja; Gerken, Michael; Klinkhammer-Schalke, Monika; Scharl, Anton; Lux, Michael P.; Beckmann, Matthias; Scharl, Sophia (Journal of Cancer Research and Clinical Oncology, 2018)
The recommended therapy for type I FIGO IB endometrial cancer (EC) is hysterectomy and adnexectomy, but the therapeutic benefits of additional pelvic and paraaortic lymph node dissection (LND) are still under discussion. In this study, we retrospectively evaluated overall survival (OAS) and recurrence-free survival (RFS) among patients with type I FIGO IB EC who did undergo systematic or elective lymphadenectomy or none at all.We selected 299 individuals from the database of the German Tumor Centre Regensburg who were diagnosed between 1998 and 2015 with endometrial adenocarcinoma of the uterus type I FIGO IB. We applied multivariable Cox regression to the selected patient data and estimated hazard ratios for OAS and RFS against the performed intervention. Further, we carried out risk adjustments with respect to clinicopathological parameters, and performed model selection using conditional stepwise forward selection.We observed significant benefits of LND in the unadjusted survival analysis; however, we did not confirm this effect in multivariable regression analysis upon risk adjustment. In this case, hazard ratio (HR) for OAS in patients without LND versus patients with LND is reduced to 1.214 (95% CI 0.771-1.911; p = 0.402), HR for RFS is 1.059 (95% CI 0.689-1.626; p = 0.795). Similarly, we were also able to eliminate the statistical benefit of systematic versus elective LND by risk adjustment.In contrast to previous observations in high-grade EC, our study provides compelling evidence that LND, in particular systematic lymphadenectomy, is not beneficial for patients with type I FIGO IB EC in terms of long-term OAS and RFS.
EVALuna2:92113

Is there an Advantage of Lymphadenectomy for Overall and Recurrence-Free Survival in Endometrial Carcinoma Type I FIGO IB G1-2? A Retrospective Population-Based Cohort Analysis - Hassas, Dunja; Papathemelis, Thomas; Gerken, Michael; Scharl, Sophia; Scharl, Anton; Lux, Michael P.; Beckmann, Matthias; Ortmann, Olaf; Klinkhamtner-Schalke, Monika (ONCOLOGY RESEARCH AND TREATMENT, 2020)
CRIS-Team WoS Importer:2020-03-20

IT infrastructure components to support clinical care and translational research projects in a comprehensive cancer center - Prokosch, Hans-Ulrich; Ries, Markus; Beyer, Alexander; Schwenk, Martin; Seggewies, Christof; Köpcke, Felix; Mate, Sebastian; Martin, Marcus; Bärthlein, Barbara; Beckmann, Matthias; Stürzl, Michael; Croner, Roland; et al. (User Centred Networked Health Care, 2011)
This paper presents the concept of an integrated IT infrastructure framework established at the comprehensive cancer center at the University Hospital Erlangen. The framework is based on the single source concept where data from the electronic medical record are reused for clinical and translational research projects. The applicability of the approach is illustrated by two case studies from colon cancer and prostate cancer research projects. © 2011 European Federation for Medical Informatics. All rights reserved.
UnivIS-Import:2015-04-14:Pub.2011.tech.IMMD.infome.itinfr
Keywords: Cancer documentation; Center; Comprehensive cancer; IT infrastructure framework; Single source concept; Translational research

Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk - Vachon, Celine M.; Scott, Christopher G.; Tamimi, Rulla M.; Thompson, Deborah J.; Fasching, Peter; Stone, Jennifer; Southey, Melissa C.; Winham, Stacey; Lindstrom, Sara; Lilyquist, Jenna; Giles, Graham G.; Milne, Roger L.; et al. (Breast Cancer Research, 2019)
Background: Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk.
CRIS-Team WoS Importer:2019-06-07

Joint associations of a polygenic risk score and environmental risk factors for breast cancer in the Breast Cancer Association Consortium - Rudolph, Anja; Song, Minsun; Brook, Mark N.; Milne, Roger L.; Mavaddat, Nasim; Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Wilcox, Amber N.; Hopper, John L.; Southey, Melissa C.; et al. (International Journal of Epidemiology, 2018)
Background: Polygenic risk scores (PRS) for breast cancer can be used to stratify the population into groups at substantially different levels of risk. Combining PRS and environmental risk factors will improve risk prediction; however, integrating PRS into risk prediction models requires evaluation of their joint association with known environmental risk factors. Methods: Analyses were based on data from 20 studies; datasets analysed ranged from 3453 to 23 104 invasive breast cancer cases and similar numbers of controls, depending on the analysed environmental risk factor. We evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS with reproductive history, alcohol consumption, menopausal hormone therapy (MHT), height and body mass index (BMI). We tested the null hypothesis of multiplicative joint associations for PRS and each of the environmental factors, and performed global and tail-based goodness-of-fit tests in logistic regression models. The outcomes were breast cancer overall and by estrogen receptor (ER) status. Results: The strongest evidence for a non-multiplicative joint associations with the 77-SNP PRS was for alcohol consumption (P-interaction = 0.009), adult height (P-interaction = 0.025) and current use of combined MHT (P-interaction = 0.038) in ER-positive disease. Risk associations for these factors by percentiles of PRS did not follow a clear dose-response. In addition, global and tail-based goodness of fit tests showed little evidence for departures from a multiplicative risk model, with alcohol consumption showing the strongest evidence for ER-positive disease (P = 0.013 for global and 0.18 for tail-based tests). Conclusions: The combined effects of the 77-SNP PRS and environmental risk factors for breast cancer are generally well described by a multiplicative model. Larger studies are required to confirm possible departures from the multiplicative model for individual risk factors, and assess models specific for ER-negative disease.
EVALuna2:209951

Joint genome-wide association study of endometrial cancer and ovarian cancer identifies a novel genetic risk region at 14q23.3 - O'Mara, Tracy A.; Glubb, Dylan M.; Buchanan, Daniel D.; Lambrechts, Diether; Hall, Per; Tham, Emma; Trovik, Jone; Goode, Ellen L.; Fasching, Peter; Doerk, Thilo; Scott, Rodney J.; Auer, Paul L.; et al. (CANCER RESEARCH, 2018)
CRIS-Team WoS Importer:2019-06-18

KATHERINE: Trastuzumab emtansine vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer - Mamounas, Eleftherios P.; Geyer, Charles E.; Huang, Chiun-Sheng; Mano, Max S.; Loibl, Sibylle; Untch, Michael; Wolmark, Norman; Rastogi, Priya; Schneeweiss, Andreas; Redondo, Andres; Fischer, Hans H.; Jacot, William; et al. (SWISS MEDICAL WEEKLY, 2019)
CRIS-Team WoS Importer:2019-07-19

KEYNOTE-522 Asian subgroup: Phase III study of neoadjuvant pembrolizumab (pembro) vs placebo (pbo) plus chemotherapy (chemo) followed by adjuvant pembro vs pbo for early triple-negative breast cancer (TNBC) - Dent, R.; Cortes, J.; Pusztai, L.; Mcarthur, H. L.; Kuemmel, S.; Bergh, J.; Denkert, C.; Park, Y. H.; Hui, R.; Harbeck, N.; Takahashi, M.; Foukakis, T.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2021-01-15

KEYNOTE-522: Neoadjuvant Pembrolizumab plus Chemotherapy vs Placebo plus Chemotherapy Followed by Adjuvant Pembrolizumab vs Placebo for Early-stage Triple Negative Breast Cancer - Mcarthur, Heather; Cortes, Javier; Dent, Rebecca; Pusztai, Lajos; Kuemmel, Sherko; Bergh, Jonas; Denkert, Carsten; Park, Yeon Hee; Hui, Rina; Harbeck, Nadia; Takahashi, Masato; Untch, Michael; et al. (ANNALS OF SURGICAL ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-05-20

KEYNOTE-522: Phase III study of neoadjuvant pembrolizumab D chemotherapy vs. placebo D chemotherapy, followed by adjuvant pembrolizumab vs. placebo for earlystage TNBC - Schmid, P.; Cortes, J.; Dent, R.; Pusztai, L.; Mcarthur, H.; Kummel, S.; Bergh, J.; Denkert, C.; Park, Y. H.; Hui, R.; Harbeck, N.; Takahashi, M.; et al. (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-09-03

KEYNOTE-522: Phase III study of pembrolizumab (pembro) plus chemotherapy (chemo) vs placebo (pbo) plus chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC) - Schmid, P.; Cortes, J.; Dent, R.; Pusztai, L.; Mcarthur, H. L.; Kuemmel, S.; Bergh, J.; Denkert, C.; Park, Y. H.; Hui, R.; Harbeck, N.; Takahashi, M.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Ki67, chemotherapy response, and prognosis in breast cancer patients receiving neoadjuvant treatment - Fasching, Peter A.; Heusinger, Katharina; Haeberle, Lothar; Niklos, Melitta; Hein, Alexander; Bayer, Christian M.; Rauh, Claudia; Schulz-Wendtland, Rüdiger; Bani, Mayada; Schrauder, Michael; Kahmann, Laura; Lux, Michael P.; et al. (BMC Cancer, 2011)
Background: The pathological complete response (pCR) after neoadjuvant chemotherapy is a surrogate marker for a favorable prognosis in breast cancer patients. Factors capable of predicting a pCR, such as the proliferation marker Ki67, may therefore help improve our understanding of the drug response and its effect on the prognosis. This study investigated the predictive and prognostic value of Ki67 in patients with invasive breast cancer receiving neoadjuvant treatment for breast cancer.Methods: Ki67 was stained routinely from core biopsies in 552 patients directly after the fixation and embedding process. HER2/neu, estrogen and progesterone receptors, and grading were also assessed before treatment. These data were used to construct univariate and multivariate models for predicting pCR and prognosis. The tumors were also classified by molecular phenotype to identify subgroups in which predicting pCR and prognosis with Ki67 might be feasible.Results: Using a cut-off value of > 13% positively stained cancer cells, Ki67 was found to be an independent predictor for pCR (OR 3.5; 95% CI, 1.4, 10.1) and for overall survival (HR 8.1; 95% CI, 3.3 to 20.4) and distant disease-free survival (HR 3.2; 95% CI, 1.8 to 5.9). The mean Ki67 value was 50.6 ± 23.4% in patients with pCR. Patients without a pCR had an average of 26.7 ± 22.9% positively stained cancer cells.Conclusions: Ki67 has predictive and prognostic value and is a feasible marker for clinical practice. It independently improved the prediction of treatment response and prognosis in a group of breast cancer patients receiving neoadjuvant treatment. As mean Ki67 values in patients with a pCR were very high, cut-off values in a high range above which the prognosis may be better than in patients with lower Ki67 values may be hypothesized. Larger studies will be needed in order to investigate these findings further. © 2011 Fasching et al; licensee BioMed Central Ltd.
CRIS-Team Scopus Importer:2021-07-19

Klinische Endpunkte in Real-World-Register-Studien - Hartkopf, Andreas D.; Emons, Julius; Lux, Michael P.; Taran, Florin Andrei; Overkamp, Friedrich; Tesch, Hans; Titzmann, Adriana; Pöschke, Patrik; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Beckmann, Matthias; et al. (Onkologe, 2020)
Background: The therapeutic options for the individual patient with metastatic breast cancer are becoming more and more specific. Evidence for therapeutic recommendations from clinical trials is not available for all treatment situations and patient subgroups. This makes the collection and evaluation of real-world data meaningful. Methods and aims: To provide recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research Network (PREAGNANT) has been established to optimize the oncological quality of care in the advanced therapeutic setting. The main aim is to systematically record medical care of patients with metastatic breast cancer in real life including the therapeutic effects and side effects of the different treatment strategies, to monitor the quality of life changes during therapy, to identify patients who could participate in a clinical drug study and to enable a targeted therapy based on molecular structures of breast cancer patients. Conclusion: This article presents a summary of the PRAEGNANT network and sheds light on the question of the portability of the various endpoints from clinical trials into the real world treatment situation.
CRIS-Team Scopus Importer:2020-05-08
Keywords: Artificial intelligence; Big data; Clinical decision-making; Evidence-based medicine; Information systems

KNOCK-OUT OF THE HUMAN ENDOGENOUS RETROVIRUS ERV3 USING CRISPR/CAS9 TECHNOLOGY - Hübner, Hanna; Fahlbusch, Fabian B.; Ekici, Arif Bülent; Vasileiou, Georgia; Beckmann, Matthias; Strick, Reiner; Rübner, Matthias (2016)
EVALuna2:9327

Knowledge and attitudes regarding medical research studies among patients with breast cancer and gynecological diseases - Lux, Michael P.; Hildebrandt, Thomas; Knetzger, Sandra-Maria; Schrauder, Michael G.; Jud, Sebastian; Hein, Alexander; Rauh, Claudia; Fasching, Peter; Beckmann, Matthias; Thiel, Falk (BMC Cancer, 2015)
Medical research studies are becoming increasingly important for optimizing the prevention, diagnosis and treatment of illnesses. Participation in research studies can have many benefits for patients. In randomized and controlled clinical studies, they can receive the best possible medical care currently available. However, only a small proportion of patients nowadays are treated within the framework of medical research. The primary endpoint of this study was to discover what level of knowledge patients have about clinical studies and how they currently perceive them, in order to identify ways of optimizing the information provided about studies from the patients' point of view.The study included 2546 patients (breast cancer 21.6%, gynecological cancer 8.3%, obstetrics 32.7%, endometriosis 7.8%, fertility treatment 3.2%, other benign gynecological illnesses 19.2%, no information for 7.2%) in the outpatient clinic (45.2%) and in the in-patient sector (54.8%) at the Department of Gynecology at Erlangen University Hospital and associated centers. In the single-center study, conducted between January 2011 and January 2012, the patients were asked about their level of knowledge regarding the background to medical research studies and the ways in which they are carried out and used. The patients were also asked how they perceived medical studies and how they thought study conditions might be optimized. The three-page questionnaire was included in the feedback sheet received by patients as part of the hospital's quality management system.As a whole, the group only had moderate knowledge about clinical studies. A majority of the respondents considered that studies were valuable (91.6%), but only a few were also willing to take part in them (58.4%). Knowledge and willingness to participate strongly depended on age (P < 0.001), educational level (P < 0.001) and patient group (P < 0.001). Most patients would prefer to decide about participating in studies through a discussion with their outpatient physicians.The information that patients have about clinical studies affects whether they participate in them. It is therefore extremely important for patients to be well informed, for their anxieties about participation to be relieved, and for the benefits of participation to be explained to them.
EVALuna2:17441

Korrelate der Depressivität von Müttern von Grundschulkindern - Zalan, Vera; Ziegler, Clara; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (50. Jahreskongress der Deutschen Gesellschaft für Psychologie, 2016)

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use? - Kehl, Sven; Weiss, Christel; Rath, Werner; Schneider, Michael; Stumpfe, Florian; Faschingbauer, Florian; Beckmann, Matthias; Stelzl, Patrick (Geburtshilfe und Frauenheilkunde, 2021)
Subject While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice.
CRIS-Team WoS Importer:2021-09-03

Lack of evidence for effects of lockdowns on stillbirth rates during the SARS-CoV-2 pandemic in Bavaria: analysis of the Bavarian perinatal survey from 2010 to 2020 - Stumpfe, Florian; Schneider, Michael; Antoniadis, Sophia; Mayr, Andreas; Fleckenstein, Tobias; Staerk, Christian; Kehl, Sven; Hermanek, Peter; Boehm, Julian; Scharl, Anton; Beckmann, Matthias; Hein, Alexander (Archives of Gynecology and Obstetrics, 2022)
Background: Internationally, potential effects of national SARS-CoV-2-related lockdowns on stillbirth rates have been reported, but data for Germany, including risk factors for fetal pregnancy outcome, are lacking. The aim of this study is to compare the stillbirth rates during the two first lockdown periods in 2020 with previous years from 2010 to 2019 in a large Bavarian cohort. Methods: This study is a secondary analysis of the Bavarian perinatal data from 2010 to 2020, including 349,245 births. Univariate and multivariable regression analyses were performed to investigate the effect of two Bavarian lockdowns on the stillbirth rate in 2020 compared to the corresponding periods from 2010 to 2019. Results: During the first lockdown, the stillbirth rate was significantly higher compared to the reference period (4.04 vs. 3.03 stillbirths per 1000 births; P = 0.03). After adjustment for seasonal and long-term trends, this effect can no longer be observed (P = 0.2). During the second lockdown, the stillbirth rate did not differ in univariate (3.46 vs. 2.93 stillbirths per 1000 births; P = 0.22) as well as in multivariable analyses (P = 0.68), compared to the years 2010 to 2019. Conclusion: After adjustment for known long-term effects, in this study we did not find evidence that the two Bavarian lockdowns had an effect on the rate of stillbirths.
CRIS-Team Scopus Importer:2022-11-25
Keywords: COVID-19; Stillbirths; Stillborn

Large-scale evaluation of common variation in regulatory T cell-related genes and ovarian cancer outcome - Charbonneau, Bridget; Moysich, Kirsten B.; Kalli, Kimberly R.; Oberg, Ann L.; Vierkant, Robert A.; Fogarty, Zachary C.; Block, Matthew S.; Maurer, Matthew J.; Goergen, Krista M.; Fridley, Brooke L.; Cunningham, Julie M.; Rider, David N.; et al. (Cancer Immunology Research, 2014)
The presence of regulatory T cells (Treg) in solid tumors is known to play a role in patient survival in ovarian cancer and other malignancies. We assessed inherited genetic variations via 749 tag single-nucleotide polymorphisms (SNP) in 25 Treg-associated genes (CD28, CTLA4, FOXP3, IDO1, IL10, IL10RA, IL15, 1L17RA, IL23A, IL23R, IL2RA, IL6, IL6R, IL8, LGALS1, LGALS9, MAP3K8, STAT5A, STAT5B, TGFB1, TGFB2, TGFB3, TGFBR1, TGRBR2, and TGFBR3) in relation to ovarian cancer survival. We analyzed genotype and overall survival in 10,084 women with invasive epithelial ovarian cancer, including 5,248 high-grade serous, 1,452 endometrioid, 795 clear cell, and 661 mucinous carcinoma cases of European descent across 28 studies from the Ovarian Cancer Association Consortium (OCAC). The strongest associations were found for endometrioid carcinoma and IL2RA SNPs rs11256497 [HR, 1.42; 95% confidence interval (CI), 1.22-1.64; P = 5.7 × 10(-6)], rs791587 (HR, 1.36; 95% CI, 1.17-1.57; P = 6.2 × 10(-5)), rs2476491 (HR, = 1.40; 95% CI, 1.19-1.64; P = 5.6 × 10(-5)), and rs10795763 (HR, 1.35; 95% CI, 1.17-1.57; P = 7.9 × 10(-5)), and for clear cell carcinoma and CTLA4 SNP rs231775 (HR, 0.67; 95% CI, 0.54-0.82; P = 9.3 × 10(-5)) after adjustment for age, study site, population stratification, stage, grade, and oral contraceptive use. The rs231775 allele associated with improved survival in our study also results in an amino acid change in CTLA4 and previously has been reported to be associated with autoimmune conditions. Thus, we found evidence that SNPs in genes related to Tregs seem to play a role in ovarian cancer survival, particularly in patients with clear cell and endometrioid epithelial ovarian cance
EVALuna2:9223

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair - Day, Felix R.; Ruth, Katherine S.; Thompson, Deborah J.; Lunetta, Kathryn L.; Pervjakova, Natalia; Chasman, Daniel I.; Stolk, Lisette; Finucane, Hilary K.; Sulem, Patrick; Bulik-Sullivan, Brendan; Esko, Tonu; Johnson, Andrew D.; et al. (Nature Genetics, 2015)
Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in 70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk ( 6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
EVALuna2:17562

Learning laparoscopic hysterectomy: analysis of different surgeons' individual learning curves - Schutzenduebel, Malte; Boosz, Alexander; Baev, Evgeni; Häberle, Lothar; Muller, Andreas (Archives of Gynecology and Obstetrics, 2022)
ObjectiveThe aim of this study was to examine the development of surgical skills among surgeons learning total laparoscopic hysterectomy (TLH), using differences in complication rates between surgeons with different levels of experience and analyzing the development of individual operating times. Study designThis retrospective, single-center cohort study included 576 total laparoscopic hysterectomy procedures conducted between January 2015 and December 2019 at the municipal hospital in Karlsruhe, Germany. All TLHs were performed by eight surgeons, two of whom were experienced and six inexperienced. Complications were graded using the Clavien-Dindo classification. ResultsNo differences in complication rates were seen between experienced and inexperienced surgeons. With growing numbers of procedures, most surgeons quickly became faster, leading to reduced operating times. However, experienced surgeons who had performed more than 100 procedures also became faster, not reaching a time plateau after adjustment for weight of the uterus, presurgery score, and adnexal score. ConclusionsLearning laparoscopic hysterectomy in routine practice is safe for patients, and surgeons rapidly become faster as growing numbers of procedures are performed. Operating times for experienced surgeons who have carried out more than 100 operations also improve, and a time plateau is not reached.
CRIS-Team WoS Importer:2023-01-27

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery - Phung, Minh Tung; Webb, Penelope M.; DeFazio, Anna; Fereday, Sian; Lee, Alice W.; Bowtell, David D.L.; Fasching, Peter; Goode, Ellen L.; Goodman, Marc T.; Karlan, Beth Y.; Lester, Jenny; Matsuo, Keitaro; et al. (Gynecologic Oncology, 2023)
Objective: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. Methods: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. Results: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46–0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43–0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65–1.25, p = 0.53). Conclusions: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.
CRIS-Team Scopus Importer:2022-11-25
Keywords: Lifestyle; Ovarian cancer; Primary cytoreductive surgery; Residual disease

Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis - Fu, Zhuxuan; Brooks, Maria Mori; Irvin, Sarah; Jordan, Susan; Aben, Katja K. H.; Anton-Culver, Hoda; Bandera, Elisa; Beckmann, Matthias; Berchuck, Andrew; Brooks-Wilson, Angela; Chang-Claude, Jenny; Cook, Linda S.; et al. (Journal of the National Cancer Institute, 2023)
Background The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC. Methods LOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source. Results LOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes. Conclusions LOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
CRIS-Team WoS Importer:2023-04-21

Limited Effects of SARS-CoV-2 Pandemic-related Lockdowns and Reduced Population Mobility on Preterm Birth Rates: A Secondary Analysis of Bavarian Obstetric Quality Parameters from 2010 to 2020 - Stumpfe, Florian; Schneider, Michael Oliver; Hein, Alexander; Faschingbauer, Florian; Kehl, Sven; Hermanek, Peter; Boehm, Julian; Scharl, Anton; Beckmann, Matthias; Staerk, Christian; Mayr, Andreas (Geburtshilfe und Frauenheilkunde, 2022)
Introduction International studies on preterm birth rates during COVID-19 lockdowns report different results. This study examines preterm birth rates during lockdown periods and the impact of the mobility changes of the population in Bavaria, Germany. Material and Methods This is a secondary analysis of centrally collected data on preterm births in Bavaria from 2010 to 2020. Preterm births (< 37 weeks) in singleton and twin pregnancies during two lockdowns were compared with corresponding periods in 2010 - 2019. Fisher & apos;s exact test was used to compare raw prevalence between groups. Potential effects of two fixed lockdown periods and of variable changes in population mobility on preterm birth rates in 2020 were examined using additive logistic regression models, adjusting for long-term and seasonal trends. Results Unadjusted preterm birth rates in 2020 were significantly lower for singleton pregnancies during the two lockdown periods (Lockdown 1: 5.71% vs. 6.41%; OR 0.88; p < 0.001; Lockdown 2: 5.71% vs. 6.60%; OR = 0.86; p < 0.001). However, these effects could not be confirmed after adjusting for long-term trends (Lockdown 1: adj. OR = 0.99; p = 0.73; Lockdown 2: adj. OR = 0.96; p = 0.24). For twin pregnancies, differences during lockdown were less marked (Lockdown 1: 52.99% vs. 56.26%; OR = 0.88; p = 0.15; Lockdown 2: 58.06% vs. 58.91%; OR = 0.97; p = 0.70). Reduced population mobility had no significant impact on preterm birth rates in singleton pregnancies (p = 0.14) but did have an impact on twin pregnancies (p = 0.02). Conclusions Reduced preterm birth rates during both lockdown periods in 2020 were observed for singleton and twin pregnancies. However, these effects are reduced when adjusting for long-term and seasonal trends. Reduced population mobility was associated with lower preterm birth rates in twin pregnancies.
CRIS-Team WoS Importer:2022-07-29

Local and Systemic Therapies for Breast Cancer Patients: Reducing Short-term Symptoms with the Methods of Integrative Medicine - Hack, Carolin; Voiss, P.; Lange, S.; Paul, A. E.; Conrad, S.; Dobos, G. J.; Beckmann, Matthias; Kuemmel, S. (Geburtshilfe und Frauenheilkunde, 2015)
With improved prognosis due to advances in the diagnosis and therapy of breast cancer, physicians and therapists now focus on aspects such as quality of life and the management of side effects from breast cancer treatment. Therapy- and disease-related side effects often reduce the patient's quality of life and can place a further burden on patients, with non-compliance or discontinuation of therapy a potential consequence. Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patients' wellbeing and quality of life, reducing stress, and improving patients' mood, sleeping patterns and capacity to cope with disease. Examining the impact of integrative medicine on the side effects of cancer treatment would be beyond the scope of this review. This article therefore looks at short-term side effects of cancer treatment which are usually temporary and occur during or after local and systemic therapy. The focus is on mind-body medicine, acupuncture and classic naturopathic treatments developed by Sebastian Kneipp as complementary therapies. The latter includes hydrotherapy, phytotherapy, nutritional therapy, exercise therapy and a balanced lifestyle.
EVALuna2:17601

Logbooks alone are not enough: initial experience with implementing a logbook for medical students in a clinical internship in gynecology and obstetrics - Jud, Sebastian; Cupisti, Susanne; Frobenius, Wolfgang; Benn, Sigrid; Winkler, Andrea; Antoniadis, Sophia; Beckmann, Matthias; Heindl, Felix (European Journal of Medical Research, 2020)
BACKGROUND: Logbooks are being increasingly widely used as a means of improving medical education and further training. They will in all probability continue to be mandatory in the Practical Year (PJ) in Germany even after the upcoming amendment of the Medical Licensing Regulations (ÄAppO). However, there are different approaches to their design and use, and these are also currently undergoing considerable change. This study for the first time examines and discusses the influence of logbooks on students' evaluation of a gynecology internship. METHODS: The study was based on a well-established two-part 1-week internship course, with initially unstructured morning classes on wards and duty areas, along with precisely planned afternoon classes with skills training by peer teachers and seminars supervised by duty-exempted physicians. The postgraduate lecturers were prepared for the introduction of the logbook in a special course, and the aim was to optimize morning classes by introducing learning objectives adapted to the respective locations. The effects over 38 weeks of practical training were examined in evaluations by 235 prospectively group-randomized students with and without logbooks (n = 166 and n = 66, respectively; three datasets were not evaluable). RESULTS: In the cohort comparison, the logbook group responded significantly more positively toward the internship at the start of the course (P = 0.046). In the final evaluation, however, medical supervision during the entire internship was rated significantly more poorly (P = 0.007). The logbook cohort also considered that guidance based on learning objectives was significantly worse, as was the extent to which wards and duty areas were prepared for the students (P = 0.001 and P = 0.029). CONCLUSIONS: Introducing a logbook to optimize clinical teaching in internships may raise expectations that cannot always be met. In addition to adapting the learning objectives to a general framework that is less favorable in comparison with the Practical Year, the least that is required appears to be simultaneous and continuous mentoring of the lecturers, as well as an increase in staffing resources.
CRIS-Team Scopus Importer:2020-05-26
Keywords: Gynecology; Internship; Logbook; Teaching

Longitudinal Assessment of Examiner Experience and the Accuracy of Sonographic Fetal Weight Estimation at Term - Faschingbauer, Florian; Heimrich, Jutta; Raabe, Eva; Kehl, Sven; Schneider, Michael; Schmid, Matthias; Beckmann, Matthias; Hepp, Tobias; Luebke, Anika; Mayr, Andreas; Schild, Ralf L. (Journal of Ultrasound in Medicine, 2017)
OBJECTIVES: To evaluate the influence of examiner experience on the accuracy of sonographic weight estimation and to further analyze examiners' individual learning curves. METHODS: In this multicenter study, 4613 sonographic weight estimations performed by 18 examiners at the beginning of their ultrasound training were included. To assess the effect of experience on the accuracy of weight estimation, a multivariable mixed regression model analysis was performed, with percentage error and absolute percentage error as outcome variables and the examiner, the examiner's experience (number of examinations), birth weight, gestational age, scan-to-delivery interval, and maternal body mass index as fixed effects and the perinatal center as random intercepts. To further analyze the individual learning curves of the examiners, the cumulative summation technique was used. RESULTS: Regression analyses showed a significant influence of the number of examinations on the accuracy of sonographic weight estimation after adjustment for the above-mentioned parameters (P < .001). A typical learning curve with improving accuracy was found until approximately 200 examinations. Between 200 and 300 examinations, the diagnostic performance started to deteriorate again, with a continuous decrease until the end of the study period. Cumulative summation charts representing individual learning curves varied greatly between different examiners. CONCLUSIONS: These findings indicate the great importance of continuous quality control systems in sonographic weight estimation.
EVALuna2:34214

Longitudinal Course of Short-Term Variation and Doppler Parameters in Early Onset Growth Restricted Fetuses - Baier, Friederike; Weinhold, Leonie; Stumpfe, Florian; Kehl, Sven; Pretscher, Jutta; Bayer, Christian M.; Topal, Nalan; Pontones, Constanza; Mayr, Andreas; Schild, Ralf Lothar; Schmid, Matthias; Beckmann, Matthias; et al. (Ultraschall in der Medizin, 2019)
PURPOSE: To evaluate the longitudinal pattern of fetal heart rate short term variation (STV) and Doppler indices and their correlation to each other in severe growth restricted (IUGR) fetuses. MATERIALS AND METHODS: In this retrospective study, pregnancies with a birth weight below the 10th percentile, born between 24 and 34 gestational weeks with serial Doppler measurements in combination with a computerized CTG (cCTG) with calculated STV were included. Longitudinal changes of both Doppler indices and STV values were evaluated with generalized additive models, adjusted for gestational age and the individual. For all measurements the frequency of abnormal values with regard to the time interval before delivery and Pearson correlations between Doppler indices and STV values were calculated. RESULTS: 41 fetuses with a total of 1413 observations were included. Over the course of the whole study period, regression analyses showed no significant change of STV values (p = 0.38). Only on the day of delivery, a prominent decrease was observed (mean STV d28-22: 7.97 vs. mean STV on day 0: 6.8). Doppler indices of UA and MCA showed a continuous, significant deterioration starting about three weeks prior to delivery (p = 0.007; UA and p < 0.001, MCA). Correlation between any Doppler index and STV values was poor. CONCLUSION: Fetal heart rate STV does not deteriorate continuously. Therefore, cCTG monitoring should be performed at least daily in these high-risk fetuses. Doppler indices of umbilical artery (UA) and middle cerebral artery (MCA), however, showed continuous deterioration starting about 3 weeks prior to delivery.
EVALuna2:212318

Longitudinal z Score Distribution in Sonographic Fetal Biometry: Influence of Examiner and Experience - Faschingbauer, Florian; Heimrich, Jutta; Raabe, Eva; Kehl, Sven; Schneider, Michael; Schmid, Matthias; Beckmann, Matthias; Schild, Ralf L.; Mayr, Andreas (Journal of Ultrasound in Medicine, 2017)
OBJECTIVES: To analyze the influence of examiners and their experience on the quality of biometric measurements via the evolution of z scores in a longitudinal multicenter study. METHODS: This retrospective study included 4607 sonographic fetal biometric examinations performed by 18 examiners at the beginning of their sonography training. To analyze the quality of biometric measurements, z scores comparing the individual measurements with the expected values from a standard population were computed. To investigate the effect of examiners and their experience, we applied a multivariable regression analysis via generalized additive mixed models. RESULTS: Mean z scores for biparietal diameter, abdominal circumference, and femur length were statistically different from the expected value of 0 (P < .001); no significant differences were found for head circumference measurements. Regression analyses showed a significant effect of the number of examinations on the distribution of z scores for each type of measurement. This effect yielded z score values close to the expected value of 0 at 100 to 200 examinations for all biometric measurements, indicating good consistency with the distribution of values in the reference population. Near the end of the study period, an increasing tendency toward either overestimation (head circumference) or underestimation (biparietal diameter, abdominal circumference, and femur length) was observed. CONCLUSIONS: A longitudinal analysis of the z score distribution for quality control of biometry is feasible. A prospective and automatized use of this technique could help identify potential systematic errors and therefore improve the detection rate for high-risk pregnancies.
EVALuna2:34191

Long-Term Endurance Exercise in Humans Stimulates Cell Fusion of Myoblasts along with Fusogenic Endogenous Retroviral Genes In Vivo - Frese, Sebastian; Rübner, Matthias; Suhr, Frank; Konou, Thierry M.; Tappe, Kim A.; Toigo, Marco; Jung, Hans H.; Henke, Christine; Steigleder, Ruth; Strissel, Pamela; Hübner, Hanna; Beckmann, Matthias; et al. (PLoS ONE, 2015)
Myogenesis is defined as growth, differentiation and repair of muscles where cell fusion of myoblasts to multinucleated myofibers is one major characteristic. Other cell fusion events in humans are found with bone resorbing osteoclasts and placental syncytiotrophoblasts. No unifying gene regulation for natural cell fusions has been found. We analyzed skeletal muscle biopsies of competitive cyclists for muscle-specific attributes and expression of human endogenous retrovirus (ERV) envelope genes due to their involvement in cell fusion of osteoclasts and syncytiotrophoblasts. Comparing muscle biopsies from post- with the pre-competitive seasons a significant 2.25-fold increase of myonuclei/mm fiber, a 2.38-fold decrease of fiber area/nucleus and a 3.1-fold decrease of satellite cells (SCs) occurred. We propose that during the pre-competitive season SC proliferation occurred following with increased cell fusion during the competitive season. Expression of twenty-two envelope genes of muscle biopsies demonstrated a significant increase of putative muscle-cell fusogenic genes Syncytin-1 and Syncytin-3, but also for the non-fusogenic erv3. Immunohistochemistry analyses showed that Syncytin-1 mainly localized to the sarcolemma of myofibers positive for myosin heavy-chain isotypes. Cellular receptors SLC1A4 and SLC1A5 of Syncytin-1 showed significant decrease of expression in post-competitive muscles compared with the pre-competitive season, but only SLC1A4 protein expression localized throughout the myofiber. Erv3 protein was strongly expressed throughout the myofiber, whereas envK1-7 localized to SC nuclei and myonuclei. Syncytin-1 transcription factors, PPAR? and RXR?, showed no protein expression in the myofiber, whereas the pCREB-Ser133 activator of Syncytin-1 was enriched to SC nuclei and myonuclei. Syncytin-1, Syncytin-3, SLC1A4 and PAX7 gene regulations along with MyoD1 and myogenin were verified during proliferating or actively-fusing human primary myoblast cell cultures, resembling muscle biopsies of cyclists. Myoblast treatment with anti-Synycytin-1 abrogated cell fusion in vitro. Our findings support functional roles for ERV envelope proteins, especially Syncytin-1, contributing to cell fusion of myotubes.
EVALuna2:17549

Long-term outcome of patients with intermediate- and high-risk endometrial cancer after pelvic and paraaortic lymph node dissection: a comparison of laparoscopic vs. open procedure - Papathemelis, Thomas; Oppermann, Helen; Grafl, Stella; Gerken, Michael; Pauer, Armin; Scharl, Sophia; Scharl, Anton; Inwald, Elisabeth; Ignatov, Atanas; Ortmann, Olaf; Klinkhammer-Schalke, Monika; Hein, Alexander; et al. (Journal of Cancer Research and Clinical Oncology, 2020)
Objective: The primary therapy for intermediate- and high-risk endometrial cancer includes pelvic and paraaortic lymph node evaluation. Laparoscopic surgery is an increasingly popular intervention due to decreased risk and better short-term morbidity; however, a recent study casts doubt on the benefit of this approach in terms of oncological safety. In this cancer registry study, we sought to evaluate the benefit of laparoscopy versus laparotomy and retrospectively compared overall survival, recurrence rates, and recurrence-free survival among patients with intermediate- and high-risk endometrial cancer who underwent either laparoscopic or open surgery. Methods: This observational study included 419 patients who have been treated from 2011 to 2017. We employed Kaplan–Meier method, and univariable and multivariable Cox-regression to compare overall survival, recurrence rates, and recurrence-free survival in 110 patients, who underwent laparoscopic, with 309 patients, who underwent open surgery. To address the confounding bias in this retrospective study, we also performed a propensity score matching (PSM) analysis including 357 patients (laparoscopy: n = 107; open surgery: n = 250). Results: We found a benefit for laparoscopic over open surgery in patients with intermediate- and high-risk endometrial cancer for overall survival in both univariable (p = 0.002; PSM: p = 0.016) and multivariable analyses (p = 0.019; PSM: p = 0.007). In contrast, there was no statistically significant difference between both patient groups regarding the cumulative recurrence rates. A univariable analysis identified a significant benefit for laparoscopy regarding recurrence-free survival (p = 0.003; PSM: p = 0.029) but a multivariable analysis failed to confirm this finding (p = 0.108; PSM: p = 0.118). Conclusions: Our study provides evidence that laparoscopic systematic lymphadenectomy does not present a lower oncological efficacy than open surgery in the treatment of patients with endometrial cancer.
CRIS-Team Scopus Importer:2020-01-10
Keywords: Cancer registry study; Endometrial cancer; Laparoscopy; Laparotomy; Observational study; Overall survival; Pelvic and paraaortic lymphadenectomy

Long-term survival analysis of the randomized phase II trial investigating the addition of carboplatin to neoadjuvant therapy for triple-negative (TNBC) and HER2-positive early breast cancer (GeparSixto) - Untch, M.; Schneeweiss, A.; Salat, C.; Rezai, M.; Zahm, D-M.; Klare, P.; Blohmer, J-U.; Tesch, H.; Khandan, F.; Fasching, Peter; Jackisch, C.; Nekljudova, V.; et al. (2017)
EVALuna2:36186

Long-term survival of HER2-positive breast cancer patients with brain metastases: subanalysis of the BMBC Registry - Laakmann, E.; Riecke, K.; Neunhoeffer, T.; Park-Simon, T-Wp; Weide, R.; Polasik, A.; Schmidt, M.; Puppe, J.; Fasching, Peter; Hesse, T.; Decker, T.; Denkert, C.; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

Low-dose methotrexate treatment in ectopic pregnancy: a retrospective analysis of 164 ectopic pregnancies treated between 2000 and 2008 - Lermann, Johannes; Segl, Petra; Jud, Sebastian; Beckmann, Matthias; Oppelt, Peter; Thiel, Falk; Renner, Stefan; Mueller, Andreas (Archives of Gynecology and Obstetrics, 2014)
Ectopic pregnancy is an acute, potentially life-threatening condition. The aim of this study was to compare the results of surgery and methotrexate treatment in women with ectopic pregnancy, along with a review of the literature.164 women with ectopic pregnancy, treated from 2000 to 2008 at the university gynecology department, were examined in a retrospective analysis. Patients with diagnosed ectopic pregnancy underwent one of the following treatments: Salpingotomy, salpingectomy or administration of a single dose of 30 mg methotrexate. The main outcome measures were treatment success rate, rate of patients wishing to have children after the ectopic pregnancy, and rates of pregnancy, live births, recurrent ectopic pregnancy, miscarriage, use of assisted reproduction and side effects.There were no significant differences in success rates between the groups (methotrexate 83.9 %, salpingotomy 88.2 %, salpingectomy 96.8 %). Significantly more patients in the salpingotomy group wished to become pregnant afterward than in the salpingectomy group. No significant differences were observed between the groups in the rates of intrauterine pregnancy, live births, recurrences, miscarriages, or side effects.With defined inclusion criteria, similar results can be achieved with low-dose single administration of 30 mg methotrexate in comparison with surgical treatment for ectopic pregnancy. On the basis of the data presented here, further research to establish optimal dosages for methotrexate is needed.
EVALuna2:17460

Low-Risk Women with Suspicious Microcalcifications in Mammography-Can an Additional Breast MRI Reduce the Biopsy Rate? - Pöschke, Patrik; Wenkel, Evelyn; Hack, Caroline; Beckmann, Matthias; Uder, Michael; Ohlmeyer, Sabine (Diagnostics, 2023)
Background: In the German Mammography Screening Program, 62% of ductal carcinoma in situ (DCIS) and 38% of invasive breast cancers are associated with microcalcifications (MCs). Vacuum-assisted stereotactic breast biopsies are necessary to distinguish precancerous lesions from benign calcifications because mammographic discrimination is not possible. The aim of this study was to investigate if breast magnetic resonance imaging (MRM) could assist the evaluation of MCs and thus help reduce biopsy rates. Methods: In this IRB-approved study, 58 women (mean age 58 +/- 24 years) with 59 suspicious MC clusters in the MG were eligible for this prospective single-center trial. Additional breast magnetic resonance imaging (MRI) was conducted before biopsy. Results: The breast MRI showed a sensitivity of 86%, a specificity of 84%, a positive predictive value (PPV) of 75% and a negative predictive value (NPV) of 91% for the differentiation between benign and malignant in these 59 MCs found with MG. Breast MRI in addition to MG could increase the PPV from 36% to 75% compared to MG alone. The MRI examination led to nine additional suspicious classified lesions in the study cohort. A total of 55% (5/9) of them turned out to be malignant. A total of 32 of 59 (54 %) women with suspicious MCs and benign histology were classified as non-suspicious by MRI. Conclusion: An additionally performed breast MRI could have increased the diagnostic reliability in the assessment of MCs. Further, in our small cohort, a considerable number of malignant lesions without mammographically visible MCs were revealed.
CRIS-Team WoS Importer:2023-04-14

Machine Learning-based Detection of In-Utero Fetal Presentation from Non-Invasive Fetal ECG - Jäger, Katharina; Nissen, Michael; Richer, Robert; Rahm, Simone; Titzmann, Adriana; Fasching, Peter; Eskofier, Björn; Leutheuser, Heike (2022 IEEE-EMBS International Conference on Biomedical and Health Informatics (BHI), 2022)
Preterm births account for more than 10 % of all newborns. An adverse fetal presentation is a risk factor for intrapartum and neonatal mortality. To date, no technology enables a longitudinal, ubiquitous, and unobtrusive monitoring of fetal presentation. This study presents a first approach to fetal orientation detection based on non-invasive fetal electrocardiography (NI-fECG) using the non-invasive multi-modal foetal ECG-Doppler data set for antenatal cardiology research. The data set contains 60 recordings from 39 pregnant women (21–27 weeks), including NI-fECG and ultrasound position ground truth. We evaluated both handcrafted and generic features for five different classifiers (k-Nearest-Neighbor, Decision Tree Classifier, Support Vector Classification, AdaBoost Classifier, and Multilayer Perceptron) using cross-validation on subject splits on a cleaned subset. Best results for the distinction between vertex (head down) and breech (head up) were achieved using an AdaBoost classifier with a balanced accuracy of 86.5 ± 15.0 %. With this work, we take a first step towards longitudinal fetal presentation monitoring, which contributes to a better understanding of reduced fetal movements and extends the potential applications of NI-fECG in prenatal care. In future work, we will expand our classification system to detect more detailed fetal presentations using a newly created data set.<br

Macromastia: an economic burden? A disease cost analysis based on real-world data in Germany - Jud, Sebastian; Brendle-Behnisch, Anne; Hack, Carolin; Preuss, Caroline; Arkudas, Andreas; Horch, Raymund E.; Beckmann, Matthias; Lux, Michael P. (Archives of Gynecology and Obstetrics, 2020)
Purpose: Symptomatic macromastia causes physical and psychological problems that can lead to restrictions in the patients’ social and working lives and a reduced quality of life. Associated medical treatments also have a considerable impact on health-care costs. Several studies have assessed these costs, but the total disease costs of macromastia have never been evaluated on the basis of real-world data. Methods: The data for 76 patients who underwent reduction mammoplasty between 2008 and 2016 were collected using a two-part questionnaire (preoperative and postoperative), as well as the patient files. Topics surveyed, besides demographic data, included physician visits, medical imaging, medical procedures, medical treatments, rehabilitation and convalescent measures, drug intake, medical aids, exercise activity, and sick leave days before surgery, to calculate the costs per year of conservative treatment of symptomatic macromastia. Results: The mean time from start of symptoms to surgery was 11.82 years. The data for this group of patients with symptomatic macromastia show that costs per patient amount to €1677.55 per year. These costs include medical consultation, radiological imaging, medical treatments and procedures, physical therapy and rehabilitation, medication, special brassieres, exercise classes costs for sick leave due to problems with macromastia, and travel expenses. Conclusions: These results show that considerable health-care costs arise due to macromastia with conservative treatment. Overall, macromastia costs €1677.55 per patient/year. In particular, lost productivity due to sick days and the costs of physiotherapy are factors driving the high costs.
CRIS-Team Scopus Importer:2020-11-06
Keywords: Breast reduction mammoplasty; Conservative treatment; Disease costs; Gigantomastia; Health care; Macromastia

Maillard Reaction Products Inhibit Oxidation of Human Low-Density Lipoproteins in Vitro - Dittrich, Ralf; El-Massry, Khaled Farouk; Kunz, Katrin; Rinaldi, Francesco; Peich, Carlo; Beckmann, Matthias; Pischetsrieder, Monika (Journal of Agricultural and Food Chemistry, 2003)
Dietary intake of antioxidants has been associated with a reduced risk of cardiovascular diseases, which is very likely caused by their capability of prevent oxidation of low-density lipoproteins (LDL). During food processing and storage, substances with antioxidative properties are formed by Maillard reactions. In this study, the activity of Maillard products to inhibit copper-induced oxidation of human LDL in vitro was investigated. D-Glucose was heated with an equimolar amount of glycine, L-lysine, or L-arginine, for 1 h under reflux. The increase of the antioxidative activity (AOA) of the Maillard mixtures was highly significant compared to the control mixtures. Additionally, two defined Maillard products with amino reductone structure were tested. 3-Hydroxy-4-(morpholino)-3-buten-2-one (1) and amino hexose reductone (2) showed a significant and dose dependent AOA. Compound 1 was about half as active as ascorbic acid, which served as positive control. Thus, it can be concluded that Maillard products, particularly those with amino reductone structure, have the strong potential to inhibit LDL oxidation.
UnivIS-Import:2015-03-09:Pub.2003.nat.dchph.llmch.mailla_0
Keywords: Amino hexose reductone; Amino reductones; LDL oxidation; Low-density lipoprotein; Maillard reaction

Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial - González-Martín, Antonio; Desauw, Christophe; Heitz, Florian; Cropet, Claire; Gargiulo, Piera; Berger, Regina; Ochi, Hiroyuki; Vergote, Ignace; Colombo, Nicoletta; Mirza, Mansoor R.; Tazi, Youssef; Canzler, Ulrich; et al. (European Journal of Cancer, 2022)
Background: PAOLA-1/ENGOT-ov25 (NCT02477644) demonstrated a significant progression-free survival (PFS) benefit with maintenance olaparib plus bevacizumab versus placebo plus bevacizumab in newly diagnosed, advanced ovarian cancer. We report the prespecified main second progression-free survival (PFS2) analysis for PAOLA-1. Methods: This randomised, double-blind, phase III trial was conducted in 11 countries. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were in response after first-line platinum-based chemotherapy plus bevacizumab. Patients were randomised 2:1 to olaparib (300 mg twice daily) or placebo for up to 24 months; all patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months. Primary PFS end-point was reported previously. Time from randomisation to second disease progression or death was a key secondary end-point included in the hierarchical-testing procedure. Results: After a median follow-up of 35.5 months and 36.5 months, respectively, median PFS2 was 36.5 months (olaparib plus bevacizumab) and 32.6 months (placebo plus bevacizumab), hazard ratio 0.78; 95% confidence interval (CI) 0.64–0.95; P = 0.0125. Median time to second subsequent therapy or death was 38.2 months (olaparib plus bevacizumab) and 31.5 months (placebo plus bevacizumab), hazard ratio 0.78; 95% CI 0.64–0.95; P = 0.0115. Seventy-two (27%) patients in the placebo plus bevacizumab group received a poly(ADP-ribose) polymerase inhibitor as first subsequent therapy. No new safety signals were observed for olaparib plus bevacizumab. Conclusion: In newly diagnosed, advanced ovarian cancer, maintenance olaparib plus bevacizumab provided continued benefit beyond first progression, with a significant PFS2 improvement and a time to second subsequent therapy or death delay versus placebo plus bevacizumab.
CRIS-Team Scopus Importer:2022-09-16
Keywords: Antiangiogenic agent; Bevacizumab; Olaparib; Ovarian cancer; PARP inhibitor; Second progression-free survival

Maintenance tocolysis: a reappraisal of clinical evidence - Stelzl, Patrick; Kehl, Sven; Rath, Werner (Archives of Gynecology and Obstetrics, 2019)
Introduction: Maintenance tocolysis, mostly defined as the continuation of tocolytic treatment beyond 48 h, remains a matter of debate. There is no sufficient evidence from randomized controlled trials, that maintenance tocolysis is able to prolong pregnancy significantly and to reduce severe neonatal morbidity and mortality. Hence, it is not recommended in current guidelines. On the contrary, maintenance tocolysis is commonly used in clinical practice and subject of current clinical-scientific investigations. Tocolytics for maintenance treatment: None of the conventional tocolytics (beta-sympathomimetics, calcium-channel blockers, magnesium, cyclooxygenase inhibitors, and oxytocin receptor antagonists) have proven to be appropriate for maintenance treatment. Progesterone and 17-α-hydroxyprogesterone caproate have shown promising results in low-quality randomized trials, but not in high-quality studies. Discussion: Basically, the value of studies regarding maintenance tocolysis is limited by a considerable heterogeneity, its mostly low quality, significant differences in methodology as well as the inadequate statistical power due to the small number of women studied. So far, maintenance tocolysis is a case-by-case decision outweighing the benefits and harms of tocolytic treatment.
CRIS-Team Scopus Importer:2019-11-05
Keywords: Efficacy; Maintenance tocolysis; Progesterone; Recommendations; Threatened preterm birth; Tocolytic agents

Major and minor complications after anterior rectal resection for deeply infiltrating endometriosis - Renner, Stefan; Kessler, Hermann; Topal, Nalan; Proske, Kim; Adler, Werner; Burghaus, Stefanie; Haupt, Werner; Beckmann, Matthias; Lermann, Johannes (Archives of Gynecology and Obstetrics, 2017)
The aim of the present study was to analyze major and minor complications-including long-term impairment of intestinal, bladder, and sexual function-following surgery for deeply infiltrating endometriosis using anterior rectal resection.Patients who had undergone anterior rectal resection due to endometriosis between 2001 and 2011 were included (n = 113). Clinical and surgical data, as well as minor and major complications, were recorded. A questionnaire was sent to the patients and also to a healthy control group (n = 100).Major complications occurred in 15.9% of cases and minor complications in 15%. Patients with postoperative ileostomies (n = 8) initially had ultralow anastomoses significantly more often. The questionnaire response rate was 77%, with a mean follow-up period of 85.9 months. Weak urinary flow was reported by 22.4% of the patients: a feeling of residual urine by 18.4%; more than one bowel movement/day by 57.5%; and insufficient lubrication during intercourse by 36.5%. These results differed significantly from the control group. Subgroup analysis showed no statistical associations between questionnaire responses and major or minor complications, ultralow anastomoses, bilateral dissection of the sacrouterine ligaments, or dissection of the vagina and rectovaginal space.The major complication rate was consistent with the literature, but there were fewer minor complications. Patients with bowel anastomoses below 6 cm (ultralow) should receive information postoperatively about the high risk of insufficiency and should be closely monitored. The high rate of bladder, bowel, and sexual function impairment, and inadequate data make further prospective studies on this topic necessary.
EVALuna2:15312

Major and minor complications after resection without bowel resection for deeply infiltrating endometriosis - Lermann, Johannes; Topal, Nalan; Adler, Werner; Hildebrandt, Thomas; Renner, Stefan P.; Beckmann, Matthias; Burghaus, Stefanie (Archives of Gynecology and Obstetrics, 2018)
PURPOSE: To analyze major and minor complications following surgery for deeply infiltrating endometriosis including long-term impairment of intestinal, bladder, and sexual function. METHODS: Patients who had undergone resection for deeply infiltrating endometriosis without anterior rectal resection between 2001 and 2011 were included (n = 134). Clinical and surgical data, as well as minor and major complications, were recorded. A questionnaire was sent to the patients and to a healthy control group (n = 100). RESULTS: Major complications occurred in 3.7% and minor complications in 12.7% of the patients. Surgical revision was necessary in five cases. The questionnaire response rate was 66.4%, with a mean follow-up period of 75.6 months. Weak urinary flow was reported by 26.4% of the patients; a feeling of residual urine by 16.1%; constipation by 13.5%; more than one bowel movement/day by 16.9%; insufficient lubrication during intercourse by 30.3%. The findings for weak urinary flow, feeling of residual urine, and insufficient lubrication differed significantly from the control group. Subgroup analysis did not identify any statistical associations between questionnaire responses and dyspareunia or dysmenorrhea as reasons for surgery, or previous endometriosis surgery in the patient's history. CONCLUSIONS: The major and minor complication rates were consistent with or lower than the literature data. Few studies have investigated complication rates associated with treatment for endometriosis in the sacrouterine ligaments and/or the rectovaginal septum. The high rates of impaired bladder function and sexual function after endometriosis surgery, as well as inadequate data, make further prospective studies on this topic necessary.
EVALuna2:35657

Mammary carcinoma in men - Preuss, Caroline; Wunderle, Marius; Hack, Carolin; Beckmann, Matthias; Wenkel, Evelyn; Jud, Sebastian; Heindl, Felix (Deutsche Medizinische Wochenschrift, 2023)
CRIS-Team WoS Importer:2023-03-31

Mammographic Density and Prediction of Nodal Status in Breast Cancer Patients - Hack, Carolin; Häberle, Lothar; Geisler, K.; Schulz-Wendtland, Rüdiger; Hartmann, Arndt; Fasching, Peter; Uder, Michael; Wachter, David; Jud, Sebastian; Löhberg, Christian; Lux, Michael P.; Rauh, Claudia; et al. (Geburtshilfe und Frauenheilkunde, 2013)
Aim: Nodal status remains one of the most important prognostic factors in breast cancer. The cellular and molecular reasons for the spread of tumor cells to the lymph nodes are not well understood and there are only few predictors in addition to tumor size and multifocality that give an insight into additional mechanisms of lymphatic spread. Aim of our study was therefore to investigate whether breast characteristics such as mammographic density (MD) add to the predictive value of the presence of lymph node metastases in patients with primary breast cancer. Methods: In this retrospective study we analyzed primary, metastasis-free breast cancer patients from one breast center for whom data on MD and staging information were available. A total of 1831 patients were included into this study. MD was assessed as percentage MD (PMD) using a semiautomated method and two readers for every patient. Multiple logistic regression analyses with nodal status as outcome were used to investigate the predictive value of PMD in addition to age, tumor size, Ki-67, estrogen receptor (ER), progesterone receptor (PR), grading, histology, and multi-focality. Results: Multifocality, tumor size, Ki-67 and grading were relevant predictors for nodal status. Adding PMD to a prediction model which included these factors did not significantly improve the prediction of nodal status (p = 0.24, likelihood ratio test). Conclusion: Nodal status could be predicted quite well with the factors multifocality, tumor size, Ki-67 and grading. PMD does not seem to play a role in the lymphatic spread of tumor cells. It could be concluded that the amount of extracellular matrix and stromal cell content of the breast which is reflected by MD does not influence the probability of malignant breast cells spreading from the primary tumor to the lymph nodes. © Georg Thieme Verlag KG Stuttgart · New York.
CRIS-Team Scopus Importer:2023-03-08
Keywords: breast cancer; estrogen receptor; Ki-67; mammographic density; nodal status; progesterone receptor

Mammographic Density and Prognosis in Patients with primary Breast Cancer - Loss of Risk with increasing Age - Heindl, Felix; Fasching, Peter; Hein, Alexander; Hack, Caroline; Heusinger, K.; Gaß, Paul; Schulz-Wendtland, Rüdiger; Hartmann, Arndt; Erber, Ramona; Beckmann, Matthias; Meyer, J.; Häberle, Lothar; et al. (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Mammographic density and prognosis in primary breast cancer patients - Heindl, Felix; Fasching, Peter; Hein, Alexander; Hack, Carolin; Heusinger, Katharina; Gaß, Paul; Pöschke, Patrik; Stübs, Frederik; Schulz-Wendtland, Rüdiger; Hartmann, Arndt; Erber, Ramona; Beckmann, Matthias; et al. (BREAST, 2021)
Purpose: Mammographic density (MD) is one of the strongest risk factors for breast cancer (BC). However, the influence of MD on the BC prognosis is unclear. The objective of this study was therefore to investigate whether percentage MD (PMD) is associated with a difference in disease-free or overall survival in primary BC patients. Methods: A total of 2525 patients with primary, metastasis-free BC were followed up retrospectively for this analysis. For all patients, PMD was evaluated by two readers using a semi-automated method. The association between PMD and prognosis was evaluated using Cox regression models with disease-free survival (DFS) and overall survival (OS) as the outcome, and the following adjustments: age at diagnosis, year of diagnosis, body mass index, tumor stage, grading, lymph node status, hormone receptor and HER2 status. Results: After median observation periods of 9.5 and 10.0 years, no influence of PMD on DFS (p = 0.46, likelihood ratio test (LRT)) or OS (p = 0.22, LRT), respectively, was found. In the initial unadjusted analysis higher PMD was associated with longer DFS and OS. The effect of PMD on DFS and OS disappeared after adjustment for age and was caused by the underlying age effect. Conclusions: Although MD is one of the strongest independent risk factors for BC, in our collective PMD is not associated with disease-free and overall survival in patients with BC.
CRIS-Team Scopus Importer:2021-07-16
Keywords: Breast cancer; Breast cancer risk; Mammographic breast density; Mammographic density; Prognosis

Mammographic density as a risk factor for breast cancer in a German case-control study - Heusinger, Katharina; Löhberg, Christian; Häberle, Lothar; Jud, Sebastian; Klingsiek, Peter; Hein, Alexander; Bayer, Christian M.; Rauh, Claudia; Uder, Michael; May, Matthias; Adamietz, Boris; Schulz-Wendtland, Rüdiger; et al. (European Journal of Cancer Prevention, 2011)
Mammographic percent density (MD) is recognized as one of the strongest risk factors associated with breast cancer. This matched case-control study investigated whether MD represents an independent risk factor. Mammograms were obtained from 1025 breast cancer patients and from 520 healthy controls. MD was measured using a quantitative computer-based threshold method (0-100%). Breast cancer patients had a higher MD than healthy controls (38 vs. 32%, P<0.01). MD was significantly higher in association with factors such as age over 60 years, body mass index (BMI) of 25-30 kg/m, nulliparity or low parity (one to two births). Average MD was inversely associated with age, BMI, parity and positively associated with age at first full-term pregnancy. MD was higher in women with at least one first-degree relative affected, but only among patients and not in the group of healthy controls (P<0.01/P=0.61). In women with an MD of 25% or more, the risk of breast cancer was doubled compared with women with an MD of less than 10% (odds ratio: 2.1; 95% confidence interval: 1.3-3.4; P<0.01); in the postmenopausal subgroup, the risk was nearly tripled (odds ratio: 2.7; 95% confidence interval: 1.6-4.7; P<0.001). This study provides further evidence that MD is an important risk factor for breast cancer. These results indicate strong associations between MD and the risk of breast cancer in a matched case-control study in Germany © 2010 Wolters Kluwer Health.
CRIS-Team Scopus Importer:2021-07-19

Mammographic density is the main correlate of tumors detected on ultrasound but not on mammography - Haeberle, Lothar; Fasching, Peter; Brehm, Barbara; Heusinger, Katharina; Jud, Sebastian; Löhberg, Christian; Hack, Carolin; Preuss, Caroline; Lux, Michael P.; Hartmann, Arndt; Vachon, Celine M.; Meier-Meitinger, Martina; et al. (International Journal of Cancer, 2016)
Although mammography screening programs do not include ultrasound examinations, some diagnostic units do provide women with both mammography and ultrasonography. This article is concerned with estimating the risk of a breast cancer patient diagnosed in a hospital-based mammography unit having a tumor that is visible on ultrasound but not on mammography. A total of 1,399 women with invasive breast cancer from a hospital-based diagnostic mammography unit were included in this retrospective study. For inclusion, mammograms from the time of the primary diagnosis had to be available for computer-assisted assessment of percentage mammographic density (PMD), as well as Breast Imaging Reporting and Data System (BIRADS) assessment of mammography. In addition, ultrasound findings were available for the complete cohort as part of routine diagnostic procedures, regardless of any patient or imaging characteristics. Logistic regression analyses were conducted to identify predictors of mammography failure, defined as BIRADS assessment 1 or 2. The probability that the visibility of a tumor might be masked at diagnosis was estimated using a regression model with the identified predictors. Tumors were only visible on ultrasound in 107 cases (7.6%). PMD was the strongest predictor for mammography failure, but age, body mass index and previous breast surgery also influenced the risk, independently of the PMD. Risk probabilities ranged from 1% for a defined low-risk group up to 40% for a high-risk group. These findings might help identify women who should be offered ultrasound examinations in addition to mammography.
EVALuna2:6818

Management of Cervical Intraepithelial Neoplasia in Pregnant Women - Stübs, Frederik; Koch, Martin C.; Dietl, Anna; Schulmeyer, Carla; Behrens, Annika; Seibold, Anja; Adler, Werner; Geppert, Carol-Immanuel; Hartmann, Arndt; Knöll, Antje; Beckmann, Matthias; Gaß, Paul; et al. (Anticancer Research, 2023)
BACKGROUND/AIM: The aims of the present study were to evaluate the accuracy of colposcopic findings, investigate the way in which untreated cervical intraepithelial neoplasia (CIN) 2/3 develops during pregnancy, and identify factors associated with regression, persistence, or progression rates. PATIENTS AND METHODS: In a tertiary gynecology and obstetrics department, 655 pregnant women were seen for colposcopy. The most common reason for referral was abnormal cytology findings. The follow-up findings were analyzed retrospectively on the basis of colposcopic findings and cytological and histological tests. RESULTS: The rate of accuracy for major colposcopic findings was 89.2%. Among the colposcopic findings considered "suspicious for invasion" were invasive carcinoma in 42.9% and CIN 3 in 57.1%. The persistence of CIN 3 postpartum was 80% and the rate of progression 4.1%. The rate of regression for CIN 3 was 21.9%. For CIN 2, the rate of persistence was 37.5%, with a regression rate of 31.3%. The rate of regression was higher after vaginal delivery in comparison with caesarean section. CONCLUSION: The accuracy rate of colposcopy is comparatively high, at 89.2%. This might be because pregnant women are seen by more experienced examiners in our dysplasia unit. The rate of progression is comparable with that in other studies. Vaginal delivery increases the regression rate. The newborns' birth weight or birth week did not affect the rates of regression or persistence.
CRIS-Team Scopus Importer:2023-07-07
Keywords: cervical dysplasia; High-grade squamous intraepithelial lesion (HSIL); mode of delivery; pregnancy; treatment

Management of Uterus bicornis unicollis with a right-sided Outflow Obstruction in a 13-year-old Girl - Lubrich, Hannah; Pontones, Constanza; Koch, Matthias; Fahlbusch, C.; Oppelt, Patricia; Beckmann, Matthias (GEBURTSHILFE UND FRAUENHEILKUNDE, 2020)
CRIS-Team WoS Importer:2020-10-30

Management operations- und karzinombedingter Blutungen - Emons, Julius; Heindl, Felix; Hein, Alexander; Beckmann, Matthias (Gynäkologe, 2016)
Background: Bleeding is a symptom in many gynecologic and obstetric diseases. Perioperative hemorrhage and bleeding in cancer patients are extraordinary situations in gynecological patients. An acute abdomen in oncological patients also requires differential diagnosis of symptoms caused by advanced cancers. Perioperative hemorrhage: Perioperative gynecologic hemorrhage is still an acute emergency requiring immediate action. Preoperative identification of patients with increased bleeding risk by thorough anamnesis is essential. Local hemostasis and, if needed, systemic treatment for underlying coagulopathies are essential to treat acute intraabdominal bleeding. Postoperative bleeding is diagnosed by clinical and instrument-based techniques and demands immediate treatment. Tumor bleeding: Bleeding occurs in patients with early and end-stage gynecologic cancers and requires – depending on the underlying cancer and clinical stage – surgical, conservative, interventional, or radiotherapeutic treatment. Acute abdomen in cancer patients: For gynecologic oncologic patients, both tumor-associated and classic causes for acute abdomen must be taken into account.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Acute abdomen; Blood coagulation factors; Blood transfusion; Hemostasis; Postoperative hemorrhage

Margetuximab Versus Trastuzumab in Patients With Previously Treated HER2-Positive Advanced Breast Cancer (SOPHIA): Final Overall Survival Results From a Randomized Phase 3 Trial - Rugo, Hope S.; Im, Seock Ah; Cardoso, Fatima; Cortes, Javier; Curigliano, Giuseppe; Musolino, Antonino; Pegram, Mark D.; Bachelot, Thomas; Wright, Gail S.; Saura, Cristina; Escrivá-de-Romaní, Santiago; De Laurentiis, Michelino; et al. (Journal of Clinical Oncology, 2023)
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Final overall survival (OS) in SOPHIA (ClinicalTrials.gov identifier: NCT02492711), a study of margetuximab versus trastuzumab, both with chemotherapy, in patients with previously treated human epidermal growth factor receptor 2-positive advanced breast cancer, is reported with updated safety. Overall, 536 patients in the intention-to-treat population were randomly assigned to margetuximab (15 mg/kg intravenously once every 3 weeks; n = 266) plus chemotherapy or trastuzumab (6 mg/kg intravenously once every 3 weeks after a loading dose of 8 mg/kg; n = 270) plus chemotherapy. Primary end points were progression-free survival, previously reported, and OS. Final OS analysis was triggered by 385 prespecified events. The median OS was 21.6 months (95% CI, 18.89 to 25.07) with margetuximab versus 21.9 months (95% CI, 18.69 to 24.18) with trastuzumab (hazard ratio [HR], 0.95; 95% CI, 0.77 to 1.17; P = .620). Preplanned, exploratory analysis of CD16A genotyping suggested a possible improvement in OS for margetuximab in CD16A-158FF patients versus trastuzumab (median OS, 23.6 v 19.2 months; HR, 0.72; 95% CI, 0.52 to 1.00) and a possible improvement in OS for trastuzumab in CD16A-158VV patients versus margetuximab (median OS, 31.1 v 22.0 months; HR, 1.77; 95% CI, 1.01 to 3.12). Margetuximab safety was comparable with trastuzumab. Final overall OS analysis did not demonstrate margetuximab advantage over trastuzumab. Margetuximab studies in patients with human epidermal growth factor receptor 2-positive breast cancer with different CD16A allelic variants are warranted.
CRIS-Team Scopus Importer:2023-01-13

Matching adjusted indirect comparison of PFS & OS comparing ribociclib plus letrozole vs palbociclib plus letrozole as first-line treatment of HR+/HER2-ABC: Analysis based on updated PFS & final OS results of MONALEESA-2 & PALOMA-2 - Jhaveri, K.; O'Shaughnessy, J.; Fasching, Peter; Cardoso, F.; Tolaney, S.; Hamilton, E.; Sharma, V. K.; Biswas, C.; Haftchenary, S.; Pathak, P.; Rugo, H. (EUROPEAN JOURNAL OF CANCER, 2022)
CRIS-Team WoS Importer:2023-03-10

Matching-Adjusted Indirect Comparison of Ribociclib Plus Fulvestrant versus Palbociclib Plus Letrozole as First-Line Treatment of HR+/HER2-Advanced Breast Cancer - Fasching, Peter; Delea, Thomas E.; Lu, Yen-Shen; De Boer, Richard; Hurvitz, Sara A.; Moynahan, Aaron; Chandiwana, David; Lanoue, Brad; Hu, Huilin; Thuerigen, Astrid; O'Shaughnessy, Joyce (Cancer Management and Research, 2021)
Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy are recommended for first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, not all CDK4/6i trials have reported significant overall survival (OS) benefit, and there have been no head-to-head trials. Two trials have reported OS outcomes in first-line patients: MONALEESA-3 reported significant OS benefit with first-or second-line ribociclib plus fulvestrant (RIB+FUL) versus placebo plus fulvestrant (PBO+FUL), while PALOMA-1 reported no significant OS benefit for palbociclib plus letrozole (PAL+LET) versus LET in first-line postmenopausal patients. Matched-adjusted indirect comparisons (MAICs) are an established method for comparing efficacy of treatments from different trials. We used an MAIC to compare first-line patients from MONALEESA-3 and PALOMA-1. Patients and Methods: An unanchored MAIC of progression-free survival (PFS) and OS in first-line patients with HR+/HER2- ABC treated with RIB+FUL versus PAL+LET was con-ducted using individual patient data from MONALEESA-3 and aggregated data from PALOMA-1. To match patients in PALOMA-1, patients in MONALEESA-3 were limited to those with no prior endocrine therapy for ABC and no (neo) adjuvant LET <= 12 months before enrollment. PFS and OS were compared using Kaplan-Meier estimators and Cox regression. Results: A total of 329 and 178 patients from RIB+FUL and PBO+FUL arms, respectively, of MONALEESA-3 were matched to 84 and 81 patients from PAL+LET and LET arms of PALOMA-1. After weighting, OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32-0.77; p = 0.0020). PFS favored RIB+FUL versus PAL+LET, although the difference was not statistically significant (HR, 0.77; 95% CI, 0.54-1.10; p = 0.1553). Conclusion: Using MAIC to adjust for trial differences, OS comparisons favored RIB+FUL over PAL+LET as first-line treatment in postmenopausal patients with HR+/HER2- ABC. These exploratory results suggest a significant increase in OS benefit with RIB treatment compared with PAL.
CRIS-Team WoS Importer:2021-11-26

Maternal Attachment Style and her Perinatal Wellbeing Influence Early Childhood Development - Goecke, Tamme W.; Schoeberl, Gudrun; Beckmann, Matthias; Beetz, Andrea M. (Zeitschrift für Geburtshilfe und Neonatologie, 2022)
An increasing number of children show signs of behavioral problems and dysregulation in early childhood. It is assumed that maternal depression and her attachment representations affect child development. This was investigated in a prospective study with 161 primiparae women. Via standardized questionnaires during the third trimester, 3 weeks, 6 months and 18 months postpartum, prenatal attachment of the mother to the unborn child, her general attachment style and postpartum depression as well as the child's dysregulation at 18 months were assessed. In the GLM, longer-lasting pre- and postpartum depressivity and insecure partnership attachment representation were associated with child dysregulation. Therefore, early detection of pre- and postpartum depression is important in order to support both the affected women and the children for better child development.
CRIS-Team WoS Importer:2022-07-29

Maternal C-reactive protein and in vitro fertilization (IVF) cycles - Diba-Bagtash, Fatemeh; Farshbaf-Khalili, Azizeh; Ghasemzadeh, Alyeh; Lotz, Laura; Fattahi, Amir; Shahnazi, Mahnaz; Dittrich, Ralf (Journal of Assisted Reproduction and Genetics, 2020)
Embryo implantation is accompanied by a potent inflammatory response, and a gradient of cytokines and chemokines produced by endometrial cells supports the embryo-endometrial interaction. C-reactive protein (CRP) serves as an early marker of inflammation and recent studies have illustrated that controlled ovarian hyperstimulation (COH) could increase its levels. Interestingly, a high chance of pregnancy has been reported in women who had an elevated CRP level on the day of embryo transfer. It seems an elevated systemic inflammation in the in vitro fertilization (IVF) cycle can increase the implantation and pregnancy rates. However, the results regarding the association of CRP with ART outcomes are controversial. Therefore, in this review, we aimed to describe how CRP levels change during a cycle of IVF treatment and which factors can potentially affect this pattern of change. Furthermore, the association of CRP with ART outcomes has been discussed.
CRIS-Team Scopus Importer:2020-08-28
Keywords: ART; Biomarker; CRP; Embryo implantation; Reproductive

Maternal depression and child development: A prospective analysis of consequences, risk and protective factors - Roetner, Jakob; Petry, Janna; Niekamp, Julia; Maschkel, Janina; Goecke, Tamme W.; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Kratz, Oliver; Moll, Gunther; Eichler, Anna (Zeitschrift für Kinder- und Jugendpsychiatrie und Psychotherapie, 2022)
Maternal depression and child development: A prospective analysis of consequences, risk and protective factors Abstract. Objective: Maternal stress, specifically maternal mental health problems, are considered risk factors for child development. The literature suggests that prenatal depressive symptoms as well as depressive symptoms are a widespread phenomenon during the further development of the child and have repeatedly been shown to have adverse effects on child mental health outcomes. The present study examined the longitudinal relationships between maternal depression (prenatal, postnatal, during childhood and adolescence) and child mental health from childhood to adolescence. Possible risk and protective factors were also considered. Method: N = 112 mothers were assessed for depressive symptoms via a questionnaire at four different timepoints (prenatal, T1; postnatal, T2; during childhood, T3; during adolescence, T4). Children's externalizing and internalizing symptoms (50.9 % girls) were assessed by their mothers both during childhood (M = 7.68, SD = 0.76 years) and during adolescence (M = 13.23, SD = 0.27 years). We evaluated the relationships between maternal depressive symptoms and children's externalizing/internalizing symptoms using multiple regression models and analyzed possible risk and protective factors using moderation analysis. Results: Externalizing/Internalizing symptoms were not directly associated with maternal depressive symptoms, while associations between such symptoms and maladaptive behavior were found in adolescents. The socioeconomic status of families showed a different risk profile for prenatal and postnatal depressive symptoms. The IQ of the children proved to be a risk factor for internalizing symptoms. Conclusions: Maternal depressive symptoms at any time during child development - in combination with further risk factors - have an impact on child mental health. The early identification of maternal symptoms followed by interventions to differentiate between prenatal and postnatal depression - especially in the context of socioeconomic status - are highly relevant for child development.
CRIS-Team WoS Importer:2022-04-08
Keywords: Pränatale Depressivität; kindliche Erlebens- und Verhaltensauffälligkeiten; Risiko- und Schutzfaktoren; sozioökonomischer Status; Intelligenzquotient; Prenatal depression; child behavior; risk and protective factors; socioeconomic status; intelligence quotient

Maternal perinatal or current depressive symptoms and parenting behavior in middle childhood - Zalan, Vera; Ziegler, Clara; Eichler, Anna; Heinrich, Hartmut; Moll, Gunther; Fasching, Peter; Beckmann, Matthias; Kornhuber, Johannes; Lenz, Bernd; Spangler, Gottfried (International Attachment Conference, 2017)

MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma - Kang, Eun Young; Millstein, Joshua; Popovic, Gordana; Meagher, Nicola S.; Bolithon, Adelyn; Talhouk, Aline; Chiu, Derek S.; Anglesio, Michael S.; Leung, Betty; Tang, Katrina; Lambie, Neil; Pavanello, Marina; et al. (Virchows Archiv, 2021)
Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naive HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naive tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naive HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.
CRIS-Team WoS Importer:2021-11-26

Me2SO perfusion time for whole-organ cryopreservation can be shortened: Results of micro-computed tomography monitoring during Me2SO perfusion of rat hearts - Bleisinger, Nathalie; Dittrich, Ralf; Strahl, Olga; Brauweiler, Robert; Hoffmann, Inge; Beckmann, Matthias; Volk, Tilmann (PLoS ONE, 2020)
Cryopreservation of whole organs and specific tissues is an important and continually expanding field of medicine. The protocols currently used for organ preservation do not ensure survivability and functionality; the protocols for ovarian tissue lead to acceptable outcomes, but these are still capable of further improvement. In general, cryopreservation protocols need to be optimized. One important approach to improving cryopreservation protocols in general involves reducing exposure to cytotoxic cryoprotective agents prior to freezing. This study, therefore, evaluated the real-time tissue penetration of dimethyl sulfoxide, a cryoprotective agent that is widely used in cryopreservation. Dimethyl sulfoxide penetration in rat hearts perfused with a 15% (v/v) dimethyl sulfoxide solution was examined in real-time using dynamic contrast-enhanced micro-computed tomography imaging. Viability of cardiomyocytes was not significantly affected by the dimethyl sulfoxide perfusion procedure. Two different perfusion rates were evaluated and compared with perfusion using a common iodine-based contrast agent (iomeprol). The dynamic contrast-enhanced micro-computed tomography imaging data showed that dimethyl sulfoxide flushes both the extracellular and intracellular spaces in rat heart tissue to 95% equilibration after ≈ 35 s via perfusion. Subsequent wash-out via perfusion is completed to 95% within ≈ 49 s. The equilibration duration routinely used in dimethyl sulfoxide-based protocols for cryopreservation should therefore be questioned. Shorter incubation duration would perhaps be sufficient, as well as being beneficial in relation to cell survivability. It would be helpful to have techniques for non-invasive real-time monitoring of the penetration of cryoprotective agents and such techniques should be used to revise cryopreservation protocols. Switching to perfusion-based equilibration procedures might be beneficial, if feasible.
CRIS-Team Scopus Importer:2020-09-11

Meconium indicators of maternal alcohol abuse during pregnancy and association with patient characteristics - Goecke, Tamme W.; Burger, Pascal; Fasching, Peter; Bakdash, Abdulsallam; Engel, Anne; Haeberle, Lothar; Voigt, Franziska; Faschingbauer, Florian; Raabe, Eva; Maass, Nicolai; Rothe, Michael; Beckmann, Matthias; et al. (BioMed Research International, 2014)
Identification of women with moderate alcohol abuse during pregnancy is difficult. We correlated self-reported alcohol consumption during pregnancy and patient characteristics with objective alcohol indicators measured in fetal meconium.A total of 557 women singleton births and available psychological tests, obstetric data and meconium samples were included in statistical analysis. Alcohol metabolites (fatty acid ethyl esters (FAEEs) and ethyl glucuronide (EtG)), were determined from meconium and correlated with patient characteristics.We found that 21.2% of the 557 participants admitted low-to-moderate alcohol consumption during pregnancy. Of the parameters analyzed from meconium, only EtG showed an association with alcohol history (P < 0.01). This association was inverse in cases with EtG value above 120 ng/g. These values indicate women with most severe alcohol consumption, who obviously denied having consumed alcohol during pregnancy. No other associations between socioeconomic or psychological characteristics and the drinking status (via meconium alcohol metabolites) could be found.Women who drink higher doses of ethanol during pregnancy, according to metabolite measures in meconium, might be less likely to admit alcohol consumption. No profile of socioeconomic or psychological characteristics of those women positively tested via meconium could be established.
EVALuna2:17357

Medication safety in patients treated with new oral antitumor agents: A prospective, randomized investigation on the impact of intensified clinical pharmaceutical/clinical pharmacological care on patient safety, patient knowledge and patient well-being (AMBORA). Supported by the German Cancer Aid within the Comprehensive Cancer Center Erlangen-EMN - Schlichtig, Katja; Lechner, P.; Grafe, Carolin; Ferstl, B.; Fuchs, F.; Hein, Alexander; Meidenbauer, N.; Sell, C.; Semrau, S.; Pavel, Marianne Ellen; Wullich, Bernd; Neurath, Markus; et al. (2018)
EVALuna2:33795

Medikamentöse Therapie der Endometriose - Burghaus, Stefanie; Beckmann, Matthias (Die Gynäkologie, 2024)
In Germany, the progestin dienogest, the gonadotropin-releasing hormone (GnRH) agonists leuprorelin, goserelin, and nafarelin, and, since November 2023, the GnRH antagonist relugolix combination therapy (relugolix-CT) have been approved for hormonal drug therapy of endometriosis. In the first-line treatment of endometriosis, oral progestin preparations have proven effective. In second-line treatment, oral estrogen–progestin combination preparations, alternative forms of progestin administration such as the hormone coil, and GnRH agonists have proven effective. GnRH agonists have low compliance due to their range of side effects and their administration should be supplemented by add-back therapy. Another option is now treatment with the GnRH antagonist relugolix-CT following previous pharmaco- or surgical therapy. Non-hormonal drug therapy can be carried out symptomatically with analgesics such as nonsteroidal anti-inflammatory drugs.
CRIS-Team Scopus Importer:2024-02-09
Keywords: Dienogest; Estrogens; GnRH analoga; Progestins; Relugolix

Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer - Kho, Pik Fang; Amant, Frederic; Annibali, Daniela; Ashton, Katie; Attia, John; Auer, Paul L.; Beckmann, Matthias; Black, Amanda; Brinton, Louise; Buchanan, Daniel D.; Chanock, Stephen J.; Chen, Chu; et al. (International Journal of Cancer, 2020)
Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10−8) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.
CRIS-Team Scopus Importer:2020-08-14
Keywords: endometrial cancer risk; HDL cholesterol; LDL cholesterol; Mendelian randomization; triglycerides

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1 - Cheng, Timothy H. T.; Thompson, Deborah; Painter, Jodie; O'Mara, Tracy; Gorman, Maggie; Martin, Lynn; Palles, Claire; Jones, Angela; Buchanan, Daniel D.; Win, Aung Ko; Hopper, John; Jenkins, Mark; et al. (Scientific Reports, 2015)
High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10(-9)) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10(-8)), with the alleles showing opposite effects on the risks of the two cancers.
EVALuna2:9303

Meta-analysis on association of pathological complete response with long-term survival outcomes in triple-negative breast cancer - Fasching, Peter; Huang, M.; Cortes, J.; Zhao, J.; O'Shaughnessy, J.; Hu, P.; Haiderali, A.; Karantza, V.; Aktan, G.; Briggs, A.; Ramsey, S.; Qi, C. Z.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Methodological Establishment of an in-vitro ADCC Assay by using patient-specific Immune Cells - Lehle, Sarah; Völkl, Simon; Rübner, Matthias; Emons, Julius; Seitz, Katharina; Beckmann, Matthias; Fasching, Peter; Hübner, Hanna (GEBURTSHILFE UND FRAUENHEILKUNDE, 2022)
CRIS-Team WoS Importer:2022-11-04

MGMT promoter methylation in triple negative breast cancer of the GeparSixto trial - Jank, Paul; Gehlhaar, Claire; Bianca, Lederer; Caterina, Fontanella; Andreas, Schneeweiss; Karn, Thomas; Marmé, Frederik; Sinn, Hans Peter; van Mackelenbergh, Marion; Sinn, Bruno; Zahm, Dirk Michael; Ingold-Heppner, Barbara; et al. (PLoS ONE, 2020)
Triple-negative breast cancer (TNBC) is typically treated with chemotherapeutic agents, including carboplatin (Cb), an DNA platinating agent. The O6-methylguanine-DNA-methyltransferase gene (MGMT) encodes for the protein O6-alkylguanine-DNA-alkyltransferase (MGMT protein). MGMT protein is involved in DNA repair mechanisms to remove mutagenic and cytotoxic adducts from O6-guanine in DNA. In glioblastoma multiforme, MGMT methylation status is a predictive biomarker for increased response to temozolomide therapy. It has been suggested, that MGMT protein may have relevance for cellular adaptation and could have an influence on resistance to carboplatin therapy. We investigated the influence of MGMT promoter methylation on pathologic complete response and survival of patients with TNBC treated in the neoadjuvant GeparSixto trial. In 174 of 210 available TNBC tumors a valid MGMT promoter methylation status was determined by pyrosequencing of 5 CpG islands. In 21.8%, we detected a mean MGMT promoter methylation >10%. Overall, MGMT promoter methylation was not significantly associated with pathological complete response (pCR) rate. After stratification for the two therapy arms with and without Cb no statistically significant differences in therapy response rates between the two MGMT promoter methylation groups could be observed. Our results show that different MGMT promoter methylation status is not related to different chemotherapy response rates in the TNBC setting in GeparSixto.
CRIS-Team Scopus Importer:2020-09-04

MicroRNA in diagnosis and therapy monitoring of early-stage triple-negative breast cancer - Kahraman, Mustafa; Roeske, Anne; Laufer, Thomas; Fehlmann, Tobias; Backes, Christina; Kern, Fabian; Kohlhaas, Jochen; Schroers, Hannah; Saiz, Anna; Zabler, Cassandra; Ludwig, Nicole; Fasching, Peter; et al. (Scientific Reports, 2018)
Breast cancer is a heterogeneous disease with distinct molecular subtypes including the aggressive subtype triple-negative breast cancer (TNBC). We compared blood-borne miRNA signatures of early-stage basal-like (cytokeratin-CK5-positive) TNBC patients to age-matched controls. The miRNAs of TNBC patients were assessed prior to and following platinum-based neoadjuvant chemotherapy (NCT). After an exploratory genome-wide study on 21 cases and 21 controls using microarrays, the identified signatures were verified independently in two laboratories on the same and a new cohort by RT-qPCR. We differentiated the blood of TNBC patients before NCT from controls with 84% sensitivity. The most significant miRNA for this diagnostic classification was miR-126-5p (two tailed t-test p-value of 1.4 × 10-5). Validation confirmed the microarray results for all tested miRNAs. Comparing cancer patients prior to and post NCT highlighted 321 significant miRNAs (among them miR-34a, p-value of 1.2 × 10-23). Our results also suggest that changes in miRNA expression during NCT may have predictive potential to predict pathological complete response (pCR). In conclusion we report that miRNA expression measured from blood facilitates early and minimally-invasive diagnosis of basal-like TNBC. We also demonstrate that NCT has a significant influence on miRNA expression. Finally, we show that blood-borne miRNA profiles monitored over time have potential to predict pCR.
EVALuna2:209952

MicroRNA Related Polymorphisms and Breast Cancer Risk - Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L.; Muranen, Taru A.; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K.; Liu, Jianjun; Hall, Per; Irwanto, Astrid; et al. (PLoS ONE, 2014)
Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.
EVALuna2:9235

microRNAs in the pathogenesis of non-obstructive azoospermia: the underlying mechanisms and therapeutic potentials - Rezaei, Yeganeh Rastgar; Zarezadeh, Reza; Nikanfar, Saba; Oghbaei, Hajar; Nazdikbin, Nahideh; Bahrami-Asl, Zahra; Zarghami, Nosratollah; Ahmadi, Yadollah; Fattahi, Amir; Nouri, Mohammad; Dittrich, Ralf (Systems Biology in Reproductive Medicine, 2021)
miRNAs are involved in different biological processes, including proliferation, differentiation, and apoptosis. Interestingly, 38% of the X chromosome-linked miRNAs are testis-specific and have crucial roles in regulating the renewal and cell cycle of spermatogonial stem cells. Previous studies demonstrated that abnormal expression of spermatogenesis-related miRNAs could lead to nonobstructive azoospermia (NOA). Moreover, differential miRNAs expression in seminal plasma of NOA patients has been reported compared to normozoospermic men. However, the role of miRNAs in NOA pathogenesis and the underlying mechanisms have not been comprehensively studied. Therefore, the aim of this review is to mechanistically describe the role of miRNAs in the pathogenesis of NOA and discuss the possibility of using the miRNAs as therapeutic targets.
CRIS-Team WoS Importer:2021-08-20

Mindfulness-based Stress Reduction in Pregnancy: an App-Based Programme to Improve the Health of Mothers and Children (MINDFUL/PMI Study) - Lenz, Bernd; Eichler, Anna; Schwenke, Eva; Buchholz, Verena N.; Hartwig, Charlotte; Moll, Gunther; Reich, Karin; Mühle, Christiane; Volz, Bernhard; Titzmann, Adriana; Beckmann, Matthias; Heinrich, Hartmut; et al. (Geburtshilfe und Frauenheilkunde, 2018)
Unfavourable intrauterine environmental factors increase the risk of delivery complications as well as postpartum developmental and behavioural problems in children and adolescents with ongoing effects into older age. Biomarker studies show that maternal stress and the use of alcohol and tobacco during pregnancy are associated with a higher intrauterine testosterone exposure of the child. The antenatal testosterone load, in turn, is a risk factor for lasting adverse health effects which extend into adulthood. A 15-week, mindfulness-oriented, app-based programme for the reduction of stress as well as for the reduction of alcohol and tobacco use in pregnant women is established. In the monocentre, prospective, controlled, and investigator-blinded MINDFUL/PMI (Maternal Health and Infant Development in the Follow-up after Pregnancy and a Mindfulness Intervention) study, pregnant women carry out the programme. Its effect on antenatal testosterone exposure of the child is examined by assessing the index/ring finger length ratio and other biomarkers in the 1-year-old children. In addition, the programme's effects on self-regulation, the developmental status and the mental health of the children at the age of one year will be investigated. Additional aspects of the course of the pregnancy and delivery represent exploratory study objectives. This longitudinal study project is intended to improve the understanding of the impact of intrauterine environmental factors on early childhood development and health. Maternal stress as well as alcohol and tobacco use during pregnancy are modifiable factors and represent potential preventive targets.
EVALuna2:36366

miRNAs can be generally associated with human pathologies as exemplified for miR-144 - Keller, Andreas; Leidinger, Petra; Vogel, Britta; Backes, Christina; Elsharawy, Abdou; Galata, Valentina; Mueller, Sabine C.; Marquart, Sabine; Schrauder, Michael G.; Strick, Reiner; Bauer, Andrea; Wischhusen, Joerg; et al. (BMC Medicine, 2014)
miRNA profiles are promising biomarker candidates for a manifold of human pathologies, opening new avenues for diagnosis and prognosis. Beyond studies that describe miRNAs frequently as markers for specific traits, we asked whether a general pattern for miRNAs across many diseases exists.We evaluated genome-wide circulating profiles of 1,049 patients suffering from 19 different cancer and non-cancer diseases as well as unaffected controls. The results were validated on 319 individuals using qRT-PCR.We discovered 34 miRNAs with strong disease association. Among those, we found substantially decreased levels of hsa-miR-144* and hsa-miR-20b with AUC of 0.751 (95% CI: 0.703-0.799), respectively. We also discovered a set of miRNAs, including hsa-miR-155*, as rather stable markers, offering reasonable control miRNAs for future studies. The strong downregulation of hsa-miR-144* and the less variable pattern of hsa-miR-155* has been validated in a cohort of 319 samples in three different centers. Here, breast cancer as an additional disease phenotype not included in the screening phase has been included as the 20th trait.Our study on 1,368 patients including 1,049 genome-wide miRNA profiles and 319 qRT-PCR validations further underscores the high potential of specific blood-borne miRNA patterns as molecular biomarkers. Importantly, we highlight 34 miRNAs that are generally dysregulated in human pathologies. Although these markers are not specific to certain diseases they may add to the diagnosis in combination with other markers, building a specific signature. Besides these dysregulated miRNAs, we propose a set of constant miRNAs that may be used as control markers.
EVALuna2:17492

Mitomycin C and Capecitabine (MiX Trial) for Therapy of Patients with Metastasized, Breast Cancer Pretreated with Anthracycline - Almstedt, Katrin; Fasching, Peter; Scharl, Anton; Rauh, Claudia; Rack, Brigitte; Hein, Alexander; Hack, Carolin; Bayer, Christian M.; Jud, Sebastian; Schrauder, Michael G.; Beckmann, Matthias; Lux, Michael P. (Anticancer Research, 2016)
BACKGROUND/AIM: The aim of this single-arm, prospective, multicenter phase II trial (MiX) was to increase treatment options for women with metastatic breast cancer pretreated with anthracycline and taxane by evaluation of the efficacy and toxicity of the combination of mitomycin C and capecitabine. PATIENTS AND METHODS: From 03/2004 to 06/2007, a total of 39 patients were recruited and received mitomycin C in combination with capecitabine. The primary end-point was to determinate the tumor response according to Response Evaluation Criteria in Solid Tumors and the rate of toxicities (safety). The secondary study objective was the evaluation of the time to progression (i.e. efficacy). RESULTS: The median time to progression was 9.3 months (95% confidence interval=6.6-12.0 months) and the median survival was 12.8 months (95% confidence interval=6.8-18.8 months). Most treatment-related adverse events were mild to moderate. CONCLUSION: Mitomycin C and capecitabine is a good taxane-free option in patients with metastatic breast cancer previously treated with anthracycline.
EVALuna2:33006

Modern systemic therapy concepts in cervical cancer. Innovations from the S3 guideline: "Diagnosis, treatment and after care of the patient with cervical cancer" - Koch, Martin; Mehlhorn, Grit; Beckmann, Matthias (Onkologe, 2016)
The problems of uncertain treatment, mortality and morbidity rates that have not declined over the last 15 years, and the current wide variations in treatment, made necessary an upgrade from the existing Level 2k consensus-based guideline from 2008 to a Level 3 guideline. These factors also induced the current Level 3 guideline on diagnosis, treatment, and follow-up of patients with cervical carcinoma (AWMF register no. 032-033OL) since 2014. This overview describes the current standard of cervical cancer treatment. Therefore, it focusses on the drug therapy of patients suffering from cervical cancer. This is in line with the focus of the journal. A further topic is the diagnostic chain that is essential for therapeutic decision-making. Based on the recommendations of the S3 guideline, the current algorithms for treating cervical cancer are shown and discussed. Surgical procedures are mainly carried out in the early stages. From stage IIB, a simultaneous cisplatin-containing radiochemotherapy is recommended. The therapy of choice for non-operable local recurrence or metastasic situation consists of palliative chemotherapy regimens. Since 2014 the addition of a targeted therapy with bevacizumab has been integrated to the treatment approach. Therapy for patients with cervical cancer has changed significantly over the last decades. There are various new therapeutic options, which are applied according to tumour stage and on an individual basis. The decision of which therapeutic method has to be applied is based on the interdisciplinary consultation and is individualized. The patient has to be involved in the decision process. Age and life situation have to be considered as well as the stage of the disease, risk factors and the side effects of the different therapies. The aim is to provide the best quality of life and the best outcome.
EVALuna2:32954

Molecular profiling of single circulating tumor cells with diagnostic intention - Polzer, Bernhard; Medoro, Gianni; Pasch, Sophie; Fontana, Francesca; Zorzino, Laura; Pestka, Aurelia; Andergassen, Ulrich; Meier-Stiegen, Franziska; Czyz, Zbigniew T.; Alberter, Barbara; Treitschke, Steffi; Schamberger, Thomas; et al. (Embo Molecular Medicine, 2014)
Several hundred clinical trials currently explore the role of circulating tumor cell (CTC) analysis for therapy decisions, but assays are lacking for comprehensive molecular characterization of CTCs with diagnostic precision. We therefore combined a workflow for enrichment and isolation of pure CTCs with a non-random whole genome amplification method for single cells and applied it to 510 single CTCs and 189 leukocytes of 66 CTC-positive breast cancer patients. We defined a genome integrity index (GII) to identify single cells suited for molecular characterization by different molecular assays, such as diagnostic profiling of point mutations, gene amplifications and whole genomes of single cells. The reliability of > 90% for successful molecular analysis of high-quality clinical samples selected by the GII enabled assessing the molecular heterogeneity of single CTCs of metastatic breast cancer patients. We readily identified genomic disparity of potentially high relevance between primary tumors and CTCs. Microheterogeneity analysis among individual CTCs uncovered pre-existing cells resistant to ERBB2-targeted therapies suggesting ongoing microevolution at late-stage disease whose exploration may provide essential information for personalized treatment decisions and shed light into mechanisms of acquired drug resistance.
EVALuna2:6669

Molecular Subtyping of Invasive Breast Cancer Using a PAM50-Based Multigene Expression Test-Comparison with Molecular-Like Subtyping by Tumor Grade/Immunohistochemistry and Influence on Oncologist's Decision on Systemic Therapy in a Real-World Setting - Erber, Ramona; Angeloni, Miriam; Stöhr, Robert; Lux, Michael P.; Ulbrich-Gebauer, Daniel; Pelz, Enrico; Bankfalvi, Agnes; Schmid, Kurt W.; Walter, Robert F. H.; Vetter, Martina; Thomssen, Christoph; Mayr, Doris; et al. (International Journal of Molecular Sciences, 2022)
In intermediate risk hormone receptor (HR) positive, HER2 negative breast cancer (BC), the decision regarding adjuvant chemotherapy might be facilitated by multigene expression tests. In all, 142 intermediate risk BCs were investigated using the PAM50-based multigene expression test Prosigna (R) in a prospective multicentric study. In 119/142 cases, Prosigna (R) molecular subtyping was compared with local and two central (C1 and C6) molecular-like subtypes relying on both immunohistochemistry (IHC; HRs, HER2, Ki-67) and IHC + tumor grade (IHC+G) subtyping. According to local IHC, 35.4% were Luminal A-like and 64.6% Luminal B-like subtypes (local IHC+G subtype: 31.9% Luminal A-like; 68.1% Luminal B-like). In contrast to local and C1 subtyping, C6 classified >2/3 of cases as Luminal A-like. Pairwise agreement between Prosigna (R) subtyping and molecular-like subtypes was fair to moderate depending on molecular-like subtyping method and center. The best agreement was observed between Prosigna (R) (53.8% Luminal A; 44.5% Luminal B) and C1 surrogate subtyping (Cohen's kappa = 0.455). Adjuvant chemotherapy was suggested to 44.2% and 88.6% of Prosigna (R) Luminal A and Luminal B cases, respectively. Out of all Luminal A-like cases (locally IHC/IHC+G subtyping), adjuvant chemotherapy was recommended if Prosigna (R) testing classified as Prosigna (R) Luminal A at high / intermediate risk or upgraded to Prosigna (R) Luminal B.
CRIS-Team WoS Importer:2022-08-26

MUC1 (CA27.29) before and after Chemotherapy and Prognosis in High-Risk Early Breast Cancer Patients - Hübner, Hanna; Häberle, Lothar; Müller, Volkmar; Schrader, Iris; Lorenz, Ralf; Forstbauer, Helmut; Fink, Visnja; Schochter, Fabienne; Bekes, Inga; Mahner, Sven; Jückstock, Julia; Nabieva, Naiba; et al. (Cancers, 2022)
Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.
CRIS-Team Scopus Importer:2022-04-08
Keywords: anthracycline; CA15-3; CA27.29; chemotherapy; early breast cancer; MUC1; taxane; tumor marker

Multicenter evaluation of blood-based biomarkers for the detection of endometriosis and adenomyosis: A prospective non-interventional study - Burghaus, Stefanie; Drazic, Predrag; Wölfler, Monika; Mechsner, Sylvia; Zeppernick, Magdalena; Meinhold-Heerlein, Ivo; Mueller, Michael D.; Rothmund, Ralf; Vigano, Paola; Becker, Christian M.; Zondervan, Krina T.; Beckmann, Matthias; et al. (International Journal of Gynecology & Obstetrics, 2023)
Objective: To evaluate blood-based biomarkers to detect endometriosis and/or adenomyosis across nine European centers (June 2014–April 2018). Methods: This prospective, non-interventional study assessed the diagnostic accuracy of 54 blood-based biomarker immunoassays in samples from 919 women (aged 18–45 years) with suspicion of endometriosis and/or adenomyosis versus symptomatic controls. Endometriosis was stratified by revised American Society for Reproductive Medicine stage. Symptomatic controls were “pathologic symptomatic controls” or “pathology-free symptomatic controls”. The main outcome measure was receiver operating characteristic-area under the curve (ROC-AUC) and Wilcoxon P values corrected for multiple testing (q values). Results: CA-125 performed best in “all endometriosis cases” versus “all symptomatic controls” (AUC 0.645, 95% confidence interval [CI] 0.600–0.690, q < 0.001) and increased (P < 0.001) with disease stage. In “all endometriosis cases” versus “pathology-free symptomatic controls”, S100-A12 performed best (AUC 0.692, 95% CI 0.614–0.769, q = 0.001) followed by CA-125 (AUC 0.649, 95% CI 0.569–0.729, q = 0.021). In “adenomyosis only cases” versus “symptomatic controls” or “pathology-free symptomatic controls”, respectively, the top-performing biomarkers were sFRP-4 (AUC 0.615, 95% CI 0.551–0.678, q = 0.045) and S100-A12 (AUC 0.701, 95% CI 0.611–0.792, q = 0.004). Conclusion: This study concluded that no biomarkers tested could diagnose or rule out endometriosis/adenomyosis with high certainty.
CRIS-Team Scopus Importer:2023-09-29
Keywords: adenomyosis; blood-based biomarkers; CA-125; diagnosis; endometriosis; S100-A12; sFRP-4

Mutational diversity and therapy response in breast cancer-a sequencing analysis in the neoadjuvant GeparSepto trial - Loibl, Sibylle; Treue, Denise; Budczies, Jan; Weber, Karsten; Stenzinger, Albrecht; Schmitt, Wolfgang D.; Weichert, Wilko; Jank, Paul; Furlanetto, Jenny; Klauschen, Frederick; Karn, Thomas; Pfarr, Nicole; et al. (CANCER RESEARCH, 2018)
CRIS-Team WoS Importer:2019-06-18

Mutational diversity and therapy response in breast cancer: A sequencing analysis in the neoadjuvant geparsepto trial - Loibl, Sibylle; Treue, Denise; Budczies, Jan; Weber, Karsten; Stenzinger, Albrecht; Schmitt, Wolfgang D.; Weichert, Wilko; Jank, Paul; Furlanetto, Jenny; Klauschen, Frederick; Karn, Thomas; Pfarr, Nicole; et al. (Clinical Cancer Research, 2019)
Purpose: Next-generation sequencing (NGS) can be used for comprehensive investigation of molecular events in breast cancer. We evaluated the relevance of genomic alterations for response to neoadjuvant chemotherapy (NACT) in the GeparSepto trial. Experimental Design: Eight hundred fifty-one pretherapeutic formalin-fixed paraffin-embedded (FFPE) core biopsies from GeparSepto study were sequenced. The panel included 16 genes for mutational (AKT1, BRAF, CDH1, EGFR, ERBB2, ESR1, FBXW7, FGFR2, HRAS, KRAS, NRAS, SF3B1, TP53, HNF1A, PIK3CA, and PTEN) and 8 genes for copy-number alteration analysis (CCND1, ERBB2, FGFR1, PAK1, PIK3CA, TOP2A, TP53, and ZNF703). Results: The most common genomic alterations were mutations of TP53 (38.4%) and PIK3CA (21.5%), and 8 different amplifications (TOP2A 34.9%; ERBB2 30.6%; ZNF703 30.1%; TP53 21.9%; PIK3CA 24.1%; CCND1 17.7%; PAK1 14.9%; FGFR 12.6%). All other alterations had a prevalence of less than 5%. The genetic heterogeneity in different breast cancer subtypes [lum/HER2neg vs. HER2pos vs. triple-negative breast cancer (TNBC)] was significantly linked to differences in NACT response. A significantly reduced pathologic complete response rate was observed in PIK3CAmutated breast cancer [PIK3CAmut: 23.0% vs. wild-type (wt) 38.8%, P < 0.0001] in particular in the HER2pos subcohort [multivariate OR = 0.43 (95% CI, 0.24-0.79), P = 0.006]. An increased response to nab-paclitaxel was observed only in PIK3CAwt breast cancer, with univariate significance for the complete cohort (P = 0.009) and the TNBC (P = 0.013) and multivariate significance in the HER2pos subcohort (test for interaction P = 0.0074). Conclusions: High genetic heterogeneity was observed in different breast cancer subtypes. Our study shows that FFPE-based NGS can be used to identify markers of therapy resistance in clinical study cohorts. PIK3CA mutations could be a major mediator of therapy resistance in breast cancer.
CRIS-Team Scopus Importer:2019-07-12

Mutations in BRCA1/2 and Other Panel Genes in Patients With Metastatic Breast Cancer -Association With Patient and Disease Characteristics and Effect on Prognosis - Fasching, Peter; Yadav, Siddhartha; Hu, Chunling; Wunderle, Marius; Häberle, Lothar; Hart, Steven N.; Rübner, Matthias; Polley, Eric C.; Lee, Kun Y.; Gnanaolivu, Rohan D.; Hadji, Peyman; Hübner, Hanna; et al. (Journal of Clinical Oncology, 2021)
PURPOSE: Among patients with metastatic breast cancer (mBC), the frequency of germline mutations in cancer susceptibility genes and the clinical relevance of these mutations are unclear. In this study, a prospective cohort of patients with mBC was used to determine mutation rates for breast cancer (BC) predisposition genes, to evaluate the clinical characteristics of patients with mutations, and to assess the influence of mutations on patient outcome. PATIENTS AND METHODS: Germline DNA from 2,595 patients with mBC enrolled in the prospective PRAEGNANT registry was evaluated for mutations in cancer predisposition genes. The frequencies of mutations in known BC predisposition genes were compared with results from a prospective registry of patients with nonmetastatic BC sequenced using the same QIAseq method and with public reference controls. Associations between mutation status and tumor characteristics, progression-free survival, and overall survival were assessed. RESULTS: Germline mutations in 12 established BC predisposition genes (including BRCA1 and BRCA2) were detected in 271 (10.4%) patients. A mutation in BRCA1 or BRCA2 was seen in 129 patients (5.0%). BRCA1 mutation carriers had a higher proportion of brain metastasis (27.1%) compared with nonmutation carriers (12.8%). Mutations were significantly enriched in PRAEGNANT patients with mBC compared with patients with nonmetastatic BC (10.4% v 6.6%, P < .01). Mutations did not significantly modify progression-free survival or overall survival for patients with mBC. CONCLUSION: Multigene panel testing may be considered in all patients with mBC because of the high frequency of germline mutations in BRCA1/2 and other BC predisposition genes. Although the prognosis of mutation carriers and nonmutation carriers with mBC was similar, differences observed in tumor characteristics have implications for treatment and for future studies of targeted therapies.
CRIS-Team Scopus Importer:2021-06-04

Mutation status of the mediator complex subunit 12 (MED12) in uterine leiomyomas and concurrent/metachronous multifocal peritoneal smooth muscle nodules (leiomyomatosis peritonealis disseminata) - Rieker, Ralf; Agaimy, Abbas; Moskalev, Evgeny; Hebele, Simone; Hein, Alexander; Mehlhorn, Grit; Beckmann, Matthias; Hartmann, Arndt; Haller, Florian (Pathology, 2013)
Aims: The pathogenesis and classification of multicentric smooth muscle tumours with benign appearance and concurrent/metachronous uterine and peritoneal involvement is controversial and may on occasion be diagnostically challenging. Leiomyomatosis peritonealis disseminata (LPD) is a rare condition affecting women of reproductive age, characterised by the occurrence of multiple small peritoneal smooth muscle nodules with bland histology. Methods: We investigated a total of 12 uterine and seven concurrent/metachronous peritoneal smooth muscle nodules with benign appearance from two females for mutations in the mediator complex subunit 12 (MED12), which has recently been identified as the most frequent genetic aberration in uterine leiomyomas. Results: The first case harboured different MED12 mutations in the peritoneal nodules. Mutational status of peritoneal nodules was discordant with that of the uterine leiomyomas. The second case displayed the same MED12 mutation in all five peritoneal nodules, but this mutation was not detected in her current uterine leiomyomas. Conclusions: Our results suggest that smooth muscle neoplasms with benign appearance of the primary and secondary mü llerian system share a similar genetic background of MED12 mutation in combination with oestrogen dependency. Analysis of MED12 mutation status might be a valuable adjunct tool for the future classification of these sometimes diagnostically challenging multicentric tumours. © 2013 Royal College of Pathologists of Australasia.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Leiomyomatosis peritonealis disseminata; MED12; Uterine leiomyoma

MyD88 and TLR4 Expression in Epithelial Ovarian Cancer - Block, Matthew S.; Vierkant, Robert A.; Rambau, Peter F.; Winham, Stacey J.; Wagner, Philipp; Traficante, Nadia; Toloczko, Aleksandra; Tiezzi, Daniel G.; Taran, Florin Andrei; Sinn, Peter; Sieh, Weiva; Sharma, Raghwa; et al. (Mayo Clinic Proceedings, 2018)
To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival.We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong).Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P<.001 for both). In HGSOC, strong MyD88 expression was modestly associated with shortened overall survival (hazard ratio [HR], 1.13; 95% CI, 1.01-1.26; P=.04) but was also associated with advanced stage (P<.001). The expression of TLR4 was not associated with survival. In low-grade serous ovarian cancer (LGSOC), strong expression of both MyD88 and TLR4 was associated with favorable survival (HR [95% CI], 0.49 [0.29-0.84] and 0.44 [0.21-0.89], respectively; P=.009 and P=.02, respectively).Results are consistent with an association between strong MyD88 staining and advanced stage and poorer survival in HGSOC and demonstrate correlation between strong MyD88 and TLR4 staining and improved survival in LGSOC, highlighting the biological differences between the 2 serous histotypes.
EVALuna2:50245

Nab-paclitaxel improves disease-free survival in early breast cancer: GBG 69–Geparsepto - Untch, Michael; Jackisch, Christian; Schneeweiss, Andreas; Schmatloch, Sabine; Aktas, Bahriye; Denkert, Carsten; Schem, Christian; Wiebringhaus, Hermann; Kümmel, Sherko; Warm, Mathias; Fasching, Peter; Just, Marianne; et al. (Journal of Clinical Oncology, 2019)
PURPOSE The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)–paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes. METHODS Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m2 (after study amendment, 125 mg/m2) or weekly sb-paclitaxel 80 mg/m2 followed in both arms by four times epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year. RESULTS A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease–free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2. CONCLUSION The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2.
CRIS-Team Scopus Importer:2019-09-03

Nachsorge bei Patientinnen mit Zervixkarzinom - Schulmeyer, Carla; Stuebs, Frederik A.; Beckmann, Matthias (Gynäkologe, 2020)
Follow-up of patients who underwent treatment for cervical cancer starts after completion of the primary treatment. It is important in aftercare to provide the patient with care both medically, in order to detect a recurrence as soon as possible and also as psychological guidance in order to record the effects of treatment, sexuality and relationship as well as the quality of life of the patient. It is also important to provide information about offers of assistance and psycho-oncological treatment options. The type of educational procedure and the approach for special collectives, such as patients after chemo(radio)therapy or after trachelectomy, are currently under discussion.
CRIS-Team Scopus Importer:2020-12-18
Keywords: Counselling; Diagnostic imaging; Human papillomaviruses; Quality of life; Sonography

(Neo-)Adjuvant and first-line therapy: Prognostic and predictive factors (Neo-)Adjuvanten und First-Line-Therapie: Prognostische und prädiktive Faktoren - Lux, Michael P.; Oenuegoeren, Onur; Wunderle, Marius; Hein, Alexander; Rauh, Claudia; Schrauder, Michael G.; Fasching, Peter; Beckmann, Matthias (Gynäkologe, 2015)
The number of cancer cases is increasing steadily. In Germany, 97,480 women are diagnosed with a gynecological malignancy each year, which represents 43 % of all cancer cases in women. Furthermore, gynecological malignancies are responsible for 28 % of cancer deaths. These numbers highlight the need for optimal, individualized treatment decisions in order to achieve maximum effectiveness, prevent recurrence and metastatic progression, and avoid overtreatment. Reliable and validated prognostic and predictive factors are required for the therapy decision of (neo-)adjuvant or first-line treatment of patients with gynecological cancers or breast cancer. In the era of individualized and targeted therapy there are fewer predictive factors available than originally thought. Nevertheless, future perspectives for various tumor entities present promising approaches which can support therapeutic decisions for adjuvant systemic therapy, e.g. gene expression analyses, studies of gene copy variations or the detection of single mutations which play an important role in signaling pathways of tumor cells.
CRIS-Team Scopus Importer:2021-07-19
Keywords: Antineoplastic agents; Biomarkers; Breast neoplasms; Decision making; Gene expression

Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial - Von Minckwitz, Gunter; Schneeweiss, Andreas; Loibl, Sibylle; Salat, Christoph; Denkert, Carsten; Rezai, Mahdi; Blohmer, Jens U.; Jackisch, Christian; Paepke, Stefan; Gerber, Bernd; Zahm, Dirk M.; Kummel, Sherko; et al. (Lancet Oncology, 2014)
Preclinical data suggest that triple-negative breast cancers are sensitive to interstrand crosslinking agents, and that synergy may exist for the combination of a taxane, trastuzumab, and a platinum salt for HER2-positive breast cancer. We therefore aimed to assess the efficacy of the addition of carboplatin to neoadjuvant therapy for triple-negative and HER2-positive breast cancer.Patients with previously untreated, non-metastatic, stage II-III, triple-negative breast cancer and HER2-positive breast cancer were enrolled. Patients were treated for 18 weeks with paclitaxel (80 mg/m(2) once a week) and non-pegylated liposomal doxorubicin (20 mg/m(2) once a week). Patients with triple-negative breast cancer received simultaneous bevacizumab (15 mg/kg intravenously every 3 weeks). Patients with HER2-positive disease received simultaneous trastuzumab (8 mg/kg initial dose with subsequent doses of 6 mg/kg intravenously every 3 weeks) and lapatinib (750 mg daily). Patients were randomly assigned in a 1:1 ratio with dynamic allocation and minimisation, stratified by biological subtype and Ki-67 level to receive, at the same time as the backbone regimens, either carboplatin (AUC 1·5 [2·0 for the first 329 patients] once a week) or no carboplatin. The primary endpoint the proportion of patients who achieved a pathological complete response (defined as ypT0 ypN0), analysed for all patients who started treatment; a p value of less than 0·2 was deemed significant for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT01426880.296 patients were randomly assigned to receive carboplatin and 299 to no additional carboplatin, of whom 295 and 293 started treatment, respectively. In this final analysis, 129 patients (43·7%, 95% CI 38·1-49·4) in the carboplatin group achieved a pathological complete response, compared with 108 patients (36·9%, 31·3-42·4) without carboplatin (odds ratio 1·33, 95% CI 0·96-1·85; p=0·107). Of the patients with triple-negative breast cancer, 84 (53·2%, 54·4-60·9) of 158 patients achieved a pathological complete response with carboplatin, compared with 58 (36·9%, 29·4-44·5) of 157 without (p=0·005). Of the patients with HER2-positive tumours, 45 (32·8%, 25·0-40·7) of 137 patients achieved a pathological complete response with carboplatin compared with 50 (36·8%, 28·7-44·9) of 136 without (p=0·581; test for interaction p=0·015). Haematological and non-haematological toxic effects that were significantly more common in the carboplatin group than in the no-carboplatin group included grade 3 or 4 neutropenia (192 [65%] vs 79 [27%]), grade 3 or 4 anaemia (45 [15%] vs one [<1%]), grade 3 or 4 thrombocytopenia (42 [14%] vs one [<1%]), and grade 3 or 4 diarrhoea (51 [17%] vs 32 [11%]); carboplatin was more often associated with dose discontinuations (141 [48%] with carboplatin and 114 [39%] without carboplatin; p=0·031). The frequency of grade 3 or 4 haematological events decreased from 82% (n=135) to 70% (n=92) and grade 3 or 4 non-haematological events from 78% (n=128) to 59% (n=77) in the carboplatin arm when the dose of carboplatin was reduced from AUC 2·0 to 1·5.The addition of neoadjuvant carboplatin to a regimen of a taxane, an anthracycline, and targeted therapy significantly increases the proportion of patients achieving a pathological complete response. This regimen seems to increase responses in patients with triple-negative breast cancer, but not in those with HER2-positive breast cancer.GlaxoSmithKline, Roche, and Tev
EVALuna2:17513

Neoadjuvant chemotherapy in breast cancer: Which diagnostic procedures can be used? - Löhberg, Christian; Lux, Michael P.; Ackermann, Sven; Pöhls, Uwe G.; Bani, Mayada; Schulz-Wendtland, Rüdiger; Papadopoulos, Thomas; Schmucker, Martin; Beckmann, Matthias; Fasching, Peter (Anticancer Research, 2005)
BACKGROUND To improve breast cancer treatment, the evaluation of predictive factors is in the focus of clinical research. Significant discrepancies between the clinical assessment of response to neoadjuvant chemotherapy (NACT) and the pathological assessment of response from post-therapy surgical specimens have been demonstrated. We focused on comparing the value of various diagnostic methods used in medical routine. PATIENTS AND METHODS A clinical evaluation of the primary tumour and regional lymph nodes before and after NACT was performed in 139 patients by physical examination, sonography and mammography. RESULTS Mammography and physical examination correlated best with pathological findings in the measurement of the tumour, whereas sonography was the most accurate predictor of the status for axillary lymph nodes. CONCLUSION Mammography and physical examination are the best non-invasive predictors of the real size of the primary breast cancer, whereas sonography correlates better with the proven status of axillary lymph nodes.
Keywords: Neoadjuvant chemotherapy; breast cancer; mammography; sonography

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response - Loibl, S.; Schneeweiss, A.; Huober, J.; Braun, M.; Rey, J.; Blohmer, J. U.; Furlanetto, J.; Zahm, D. M.; Hanusch, C.; Thomalla, J.; Jackisch, C.; Staib, P.; et al. (Annals of Oncology, 2022)
BACKGROUND: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287). PATIENTS AND METHODS: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS). RESULTS: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred. CONCLUSIONS: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.
CRIS-Team Scopus Importer:2022-11-11
Keywords: checkpoint inhibitor; durvalumab; early triple-negative breast cancer; neoadjuvant chemotherapy; survival

Neoadjuvante Therapiekonzepte beim Zervixkarzinom - Stübs, Frederik A.; Koch, Martin; Beckmann, Matthias (Gynäkologe, 2019)
Background: The neoadjuvant treatment concept is nowadays the standard of care for many different organ entities. The neoadjuvant treatment also seems to be of interest in special situations for cervical cancer. Objective: This article gives an overview of the currently discussed fields of application of neoadjuvant therapy in treating patients with cervical cancer and the various options are discussed. Material and methods: This article is based on the national S3 guidelines for diagnostics, treatment and follow-up of patients with cervical cancer of the Association of the Scientific Medical Societies of Germany (AWMF, register number 032/033OL in the version from 2014). Additionally, this was extended by the literature for the update research of the new version of the guidelines. Results: The response rate to neoadjuvant therapy is 84%. The 5‑year progression-free survival and overall survival are 61.9% and 72.8%, respectively. Women responding to neoadjuvant therapy have a better long-term survival than non-responders. In a Cochrane meta-analysis from 2012 neoadjuvant chemotherapy before the planned operation improved the progression-free survival (hazard ratio, HR 0.75, 95% confidence interval, CI 0.61–0.93, P = 0.008) and the overall survival (HR 0.77, 95% CI 0.62–0.96, P = 0.02). The results were no longer significant when the random effects model was used (odds ratio, OR 0.60, 95% CI 0.32–1.12, P = 0.11). In macroinvasive cervical cancer during pregnancy neoadjuvant therapy is an established component of treatment. Discussion: The data on the use of neoadjuvant therapy in treating cervical cancer is unclear. The neoadjuvant therapy is currently not a standard of care in the treatment of cervical cancer. The roles of operative staging and positive lymph nodes after neoadjuvant therapy are also unresolved. Various meta-analyses could show that neoadjuvant therapy improves progression-free and overall survival. This is especially true for women who respond to this treatment.
CRIS-Team Scopus Importer:2019-05-21
Keywords: Disease progression; Disease progression; Disease-free survival; Pregnancy; Standard of care

Neoadjuvant giredestrant (GDC-9545) + palbociclib (palbo) vs anastrozole (A) plus palbo in post-menopausal women with oestrogen receptor-positive, HER2-negative, untreated early breast cancer (ER+/HER2-eBC): Interim analysis of the randomised, open-label, phase II coopERA BC study - Hurvitz, S. A.; Park, Y. H.; Bardia, A.; Quiroga, V.; Lopez-Valverde, V.; Steinseifer, J.; Moore, H. M.; Spera, G.; Xue, C.; Fasching, Peter (ANNALS OF ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-10-15

Neoadjuvant immunotherapy and chemotherapy regimens for the treatment of high-risk, early-stage triple-negative breast cancer: a systematic review and network meta-analysis - Cortes, Javier; Haiderali, Amin; Huang, Min; Pan, Wilbur; Schmid, Peter; Akers, Katherine G.; Park, Julie E.; Frederickson, Andrew M.; Fasching, Peter; O’Shaughnessy, Joyce (BMC Cancer, 2023)
Background: Patients with triple-negative breast cancer (TNBC) are generally younger and more likely to experience disease recurrence and have the shortest survival among all breast cancer patients. Recently, neoadjuvant delivery of the programmed cell death protein-1 inhibitor pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab was approved for patients with high-risk, early-stage TNBC, but this treatment regimen has not been evaluated in head-to-head trials with other neoadjuvant treatment regimens. Therefore, the objective of this study was to estimate the relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab versus other neoadjuvant treatments for early-stage TNBC through a systematic review and network meta-analysis (NMA). Methods: EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, conference abstracts, and clinical trial registries were searched for randomized controlled trials evaluating neoadjuvant treatments for early-stage TNBC. NMA was performed to estimate relative treatment effects among evaluated interventions. Results: Five trials met the inclusion criteria and were included in the NMA. The relative efficacy of neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab was favorable to paclitaxel followed by anthracycline + cyclophosphamide in terms of pathologic complete response (pCR), event-free survival (EFS), and overall survival; paclitaxel + carboplatin followed by anthracycline + cyclophosphamide in terms of pCR and EFS; paclitaxel + bevacizumab followed by anthracycline + cyclophosphamide + bevacizumab in terms of pCR; and paclitaxel + carboplatin + veliparib followed by anthracycline + cyclophosphamide in terms of EFS. Conclusions: Neoadjuvant pembrolizumab + chemotherapy followed by adjuvant pembrolizumab confers benefits in response and survival outcomes versus alternative neoadjuvant treatments for early-stage TNBC.
CRIS-Team Scopus Importer:2023-09-01
Keywords: Chemotherapy; Immunotherapy; Neoadjuvant therapy; Network meta-analysis; PD-1; PD-L1; Triple-negative breast cancer

Neoadjuvant paclitaxel/olaparib in comparison to paclitaxel/carboplatinum in patients with HER2-negative breast cancer and homologous recombination deficiency (GeparOLA study) - Fasching, Peter; Link, T.; Hauke, J.; Seither, F.; Jackisch, C.; Klare, P.; Schmatloch, S.; Hanusch, C.; Huober, J.; Stefek, A.; Seiler, S.; Schmitt, W. D.; et al. (Annals of Oncology, 2020)
Background: The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTrials.gov, NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. Patients and methods: Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN+ or pNSLN+ or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m2 weekly plus olaparib (O) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR+ versus HR−) and age (<40 versus ≥40 years). The primary endpoint was pathological complete response (pCR; ypT0/is ypN0). A two-sided one-group χ2-test was planned to exclude a pCR rate of ≤55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/imaging response, tolerability and safety. Results: A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed gBRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR+ patients. Conclusion: GeparOLA could not exclude a pCR rate of ≤55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation.
CRIS-Team Scopus Importer:2020-11-27
Keywords: carboplatinum; HER2-negative breast cancer; HRD; neoadjuvant therapy; olaparib; PARP inhibitor

Neoadjuvant palbociclib plus either giredestrant or anastrozole in oestrogen receptor-positive, HER2-negative, early breast cancer (coopERA Breast Cancer): an open-label, randomised, controlled, phase 2 study - Hurvitz, Sara A.; Bardia, Aditya; Quiroga, Vanesa; Park, Yeon Hee; Blancas, Isabel; Alonso-Romero, José Luis; Vasiliev, Aleksandr; Adamchuk, Hryhoriy; Salgado, Marcelo; Yardley, Denise A.; Berzoy, Oleksandr; Zamora-Auñón, Pilar; et al. (Lancet Oncology, 2023)
BACKGROUND: The development of more potent selective oestrogen receptor antagonists and degraders (SERDs) that can be orally administered could help to address the limitations of current endocrine therapies. We report the primary and final analyses of the coopERA Breast Cancer study, designed to test whether giredestrant, a highly potent, non-steroidal, oral SERD, would show a stronger anti-proliferative effect than anastrozole after 2 weeks for oestrogen receptor-positive, HER2-negative, untreated early breast cancer. METHODS: In this open-label, randomised, controlled, phase 2 study, postmenopausal women were eligible if they were aged 18 years or older; had clinical T stage (cT)1c to cT4a-c (≥1·5 cm within cT1c) oestrogen receptor-positive, HER2-negative, untreated early breast cancer; an Eastern Cooperative Oncology Group performance status of 0-1; and baseline Ki67 score of at least 5%. The study was conducted at 59 hospital or clinic sites in 11 countries globally. Participants were randomly assigned (1:1) to giredestrant 30 mg oral daily or anastrozole 1 mg oral daily on days 1-14 (window-of-opportunity phase) via an interactive web-based system with permuted-block randomisation with block size of four. Randomisation was stratified by cT stage, baseline Ki67 score, and progesterone receptor status. A 16-week neoadjuvant phase comprised the same regimen plus palbociclib 125 mg oral daily on days 1-21 of a 28-day cycle, for four cycles. The primary endpoint was geometric mean relative Ki67 score change from baseline to week 2 in patients with complete central Ki67 scores at baseline and week 2 (window-of-opportunity phase). Safety was assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov (NCT04436744) and is complete. FINDINGS: Between Sept 4, 2020, and June 22, 2021, 221 patients were enrolled and randomly assigned to the giredestrant plus palbociclib group (n=112; median age 62·0 years [IQR 57·0-68·5]) or anastrozole plus palbociclib group (n=109; median age 62·0 [57·0-67·0] years). 15 (7%) of 221 patients were Asian, three (1%) were Black or African American, 194 (88%) were White, and nine (4%) were unknown races. At data cutoff for the primary analysis (July 19, 2021), the geometric mean relative reduction of Ki67 from baseline to week 2 was -75% (95% CI -80 to -70) with giredestrant and -67% (-73 to -59) with anastrozole (p=0·043), meeting the primary endpoint. At the final analysis (data cutoff Nov 24, 2021), the most common grade 3-4 adverse events were neutropenia (29 [26%] of 112 in the giredestrant plus palbociclib group vs 29 [27%] of 109 in the anastrozole plus palbociclib group) and decreased neutrophil count (17 [15%] vs 16 [15%]). Serious adverse events occurred in five (4%) patients in the giredestrant plus palbociclib group and in two (2%) patients in the anastrozole plus palbociclib group. There were no treatment-related deaths. One patient died due to an adverse event in the giredestrant plus palbociclib group (myocardial infarction). INTERPRETATION: Giredestrant offers encouraging anti-proliferative and anti-tumour activity and was well tolerated, both as a single agent and in combination with palbociclib. Results justify further investigation in ongoing trials. FUNDING: F Hoffmann-La Roche.
CRIS-Team Scopus Importer:2023-09-08

Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab for treatment of high-risk, early-stage triple-negative breast cancer: A network meta-analysis - Cortes, J.; Haiderali, A.; Huang, M.; Pan, W.; Fox, G. E.; Park, J.; Frederickson, A. M.; Fasching, Peter; O'Shaughnessy, J. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-12-23

Neoadjuvant pembrolizumab plus chemotherapy versus placebo plus chemotherapy, followed by adjuvant pembrolizumab versus placebo for early-stage TNBC: Event-free survival sensitivity and subgroup analyses from KEYNOTE-522 - Schmid, Peter; Cortes, Javier; Dent, Rebecca; Pusztai, Lajos; Mcarthur, Heather; Kuemmel, Sherko; Bergh, Jonas; Denkert, Carsten; Park, Yeon Hee; Hui, Rina; Harbeck, Nadia; Takahashi, Masato; et al. (ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-11-11

Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2–positive breast cancer: Three-year outcomes from the phase III KristinE study - Hurvitz, Sara A.; Martin, Miguel; Jung, Kyung Hae; Huang, Chiun Sheng; Harbeck, Nadia; Valero, Vicente; Stroyakovskiy, Daniil; Wildiers, Hans; Campone, Mario; Boileau, Jean François; Fasching, Peter; Afenjar, Karen; et al. (Journal of Clinical Oncology, 2019)
PURPOSE The KRISTINE study compared neoadjuvant trastuzumab emtansine plus pertuzumab (T-DM1+P) with docetaxel, carboplatin, trastuzumab plus P (TCH+P) for the treatment human epidermal growth factor receptor 2–positive stage II to III breast cancer. T-DM1+P led to a lower pathologic complete response rate (44.4% v 55.7%; P = .016), but fewer grade 3 or greater and serious adverse events (AEs). Here, we present 3-year outcomes from KRISTINE. METHODS Patients were randomly assigned to neoadjuvant T-DM1+P or TCH+P every 3 weeks for six cycles. Patients who received T-DM1+P continued adjuvant T-DM1+P, and patients who received TCH+P received adjuvant trastuzumab plus pertuzumab. Secondary end points included event-free survival (EFS), overall survival, patient-reported outcomes (measured from random assignment), and invasive disease-free survival (IDFS; measured from surgery). RESULTS Of patients, 444 were randomly assigned (T-DM1+P, n = 223; TCH+P, n = 221). Median follow-up was 37 months. Risk of an EFS event was higher with TDM-1+P (hazard ratio [HR], 2.61 [95% CI, 1.36 to 4.98]) with more locoregional progression events before surgery (15 [6.7%] v 0). Risk of an IDFS event after surgery was similar between arms (HR, 1.11 [95% CI, 0.52 to 2.40]). Pathologic complete response was associated with a reduced risk of an IDFS event (HR, 0.24 [95% CI, 0.09 to 0.60]) regardless of treatment arm. Overall, grade 3 or greater AEs (31.8% v 67.7%) were less common with T-DM1+P. During adjuvant treatment, grade 3 or greater AEs (24.5% v 9.9%) and AEs leading to treatment discontinuation (18.4% v 3.8%) were more common with T-DM1+P. Patient-reported outcomes favored T-DM1+P during neoadjuvant treatment and were similar to trastuzumab plus pertuzumab during adjuvant treatment. CONCLUSION Compared with TCH+P, T-DM1+P resulted in a higher risk of an EFS event owing to locoregional progression events before surgery, a similar risk of an IDFS event, fewer grade 3 or greater AEs during neoadjuvant treatment, and more AEs leading to treatment discontinuation during adjuvant treatment.
CRIS-Team Scopus Importer:2019-09-03

Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial - Hurvitz, Sara A.; Martin, Miguel; Symmans, W. Fraser; Jung, Kyung Hae; Huang, Chiun-Sheng; Thompson, Alastair M.; Harbeck, Nadia; Valero, Vicente; Stroyakovskiy, Daniil; Wildiers, Hans; Campone, Mario; Boileau, Jean-Francois; et al. (Lancet Oncology, 2018)
BACKGROUND: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment. METHODS: We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0-1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m2; carboplatin area under the concentration-time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing. FINDINGS: Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11·3 percentage points, 95% CI -20·5 to -2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment. INTERPRETATION: Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3-4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted. FUNDING: F Hoffmann-La Roche and Genentech.
EVALuna2:36439

Neoadjuvant Treatment of Breast Cancer - Advances and Limitations - Fasching, Peter; Gaß, Paul; Hein, Alexander (Breast Care, 2016)
EVALuna2:33102

Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk - Kar, Siddhartha P.; Tyrer, Jonathan P.; Li, Qiyuan; Lawrenson, Kate; Aben, Katja K. H.; Anton-Culver, Hoda; Antonenkova, Natalia; Chenevix-Trench, Georgia; Baker, Helen; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias; et al. (Cancer Epidemiology Biomarkers & Prevention, 2015)
Genome-wide association studies (GWAS) have so far reported 12 loci associated with serous epithelial ovarian cancer (EOC) risk. We hypothesized that some of these loci function through nearby transcription factor (TF) genes and that putative target genes of these TFs as identified by coexpression may also be enriched for additional EOC risk associations.We selected TF genes within 1 Mb of the top signal at the 12 genome-wide significant risk loci. Mutual information, a form of correlation, was used to build networks of genes strongly coexpressed with each selected TF gene in the unified microarray dataset of 489 serous EOC tumors from The Cancer Genome Atlas. Genes represented in this dataset were subsequently ranked using a gene-level test based on results for germline SNPs from a serous EOC GWAS meta-analysis (2,196 cases/4,396 controls).Gene set enrichment analysis identified six networks centered on TF genes (HOXB2, HOXB5, HOXB6, HOXB7 at 17q21.32 and HOXD1, HOXD3 at 2q31) that were significantly enriched for genes from the risk-associated end of the ranked list (P < 0.05 and FDR < 0.05). These results were replicated (P < 0.05) using an independent association study (7,035 cases/21,693 controls). Genes underlying enrichment in the six networks were pooled into a combined network.We identified a HOX-centric network associated with serous EOC risk containing several genes with known or emerging roles in serous EOC development.Network analysis integrating large, context-specific datasets has the potential to offer mechanistic insights into cancer susceptibility and prioritize genes for experimental characterization. Cancer Epidemiol Biomarkers Prev; 24(10); 1574-84. ©2015 AACR.
EVALuna2:9287

Neurovascular compression of medulla oblongata - Association for gestation-induced hypertension - Tanrikulu, Levent; Naraghi, Ramin; Ernst, Veronika; Voigt, Franziska; Hastreiter, Peter; Dörfler, Arnd; Buchfelder, Michael; Beckmann, Matthias; Goecke, Tamme W. (Medical Hypotheses, 2015)
Patients with essential hypertension may show neurovascular compression (NVC) at the rostral ventrolateral medulla oblongata (RVLM). Ectatic loops of the vertebral artery (VA) or the inferior posterior cerebellar artery (PICA) cause NVC. This study aims to show the existence and morphology of NVC in patients with gestation-induced hypertension. 17 females were prospectively examined between 19. +. 0 and 35. +. 6. weeks of gestation. 3 patients with chronic hypertension (group A), 10 patients with preeclampsia (group B), 3 patients with superimposed preeclampsia (chronic hypertension with preeclampsia; group C) and one normotensive patient were included. Groups B and C represented patients with gestation-induced hypertension. All 17 patients underwent imaging by high resolution magnetic resonance imaging (MR-CISS, constructive interference in the steady state). Image processing was done with segmentation and three-dimensional (3D)-visualization was implemented with direct volume rendering of the individual neurovascular details of each patient. 9 of 17 patients (53%) showed NVC of the RVLM. Right-sided NVC was seen in 7 patients (41%). Left-sided NVC was seen in 6 patients (35%). Bilateral NVC was seen in 4 patients (24%). NVC was missing in 8 of the examined 17 patients (47%). The existence of NVC with high-resolution MRI was analyzed in gestation-induced hypertensive pregnant females for the first time. Neurovascular conflicts were seen in hypertensive pregnants. It is possible that NVC is potentially associated in patients with gestation-induced hypertension.
CRIS-Team Scopus Importer:2022-08-05

New Screening Proposals: the Federal Joint Commission Defines the Parameters for Cervical Cancer Screening from 2018 Statement of the Gynecology Oncology Working Group (AGO) - Hillemanns, P.; Mallmann, P.; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2016)
The Gynecology Oncology Working Group (AGO e.V.) unequivocally welcomes the decision taken by the German Federal Joint Commission (Gemeinsamer Bundesausschuss, G-BA) on March 19, 2015 regarding screening for cervical cancer. AGO is convinced that, in view of recent medical advances, this evidence-based decision will improve screening for cervical cancer.
EVALuna2:32998

New WHO Classification of Endometrial Hyperplasias - Emons, G.; Beckmann, Matthias; Schmidt, D.; Mallmann, P. (Geburtshilfe und Frauenheilkunde, 2015)
EVALuna2:17599

Next-generation DNA sequencing (NGS) results for tumours from phase II ABRAZO study of talazoparib after platinum or cytotoxic non-platinum regimens in patients (pts) with advanced breast cancer (ABC) and germline BRCA1/2 (gBRCA) mutations - Turner, N. C.; Laird, A. D.; Telli, M. L.; Rugo, H. S.; Mailliez, A.; Ettl, J.; Grischke, E. -M.; Mina, L. A.; Balmana, J.; Fasching, Peter; Hurvitz, S. A.; Albacker, L. A.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

NGS zur Selektion innovativer Therapien – Was bringt das? - Schulmeyer, Carla; Bader, Simon; Hübner, Hanna; Rübner, Matthias; Fasching, Peter (Gynäkologe, 2021)
Next generation sequencing (NGS) describes a technology for sequencing the entire human genome, exome and transcriptome and has revolutionized genomic research. In comparison to Sanger sequencing NGS is able to sequence a whole human genome within 1 day. The results can be aligned with reference human genomes. Through DNA fragmentation, ligation of adaptors on the ends of fragments and amplification of the fragments a bioinformatics analysis is carried out, which is stored in the form of a chip and sequenced. The NGS can be used in multiple applications, especially in genetic, microbiological and oncologic research and has not yet become comprehensively established within the clinical routine. In obstetrics and gynecology, NGS is especially used in noninvasive prenatal testing (NIPT), reproductive medicine and oncology.
CRIS-Team Scopus Importer:2021-03-19
Keywords: Breast cancer; DNA fragmentation; Genome; human; Genomics; Prenatal diagnostics

Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates - Van Der Ven, H.; Liebenthron, J.; Beckmann, Matthias; Toth, B.; Korell, M.; Kruessel, J.; Frambach, T.; Kupka, M.; Hohl, M. K.; Winkler-Crepaz, K.; Seitz, S.; Dogan, A.; et al. (Human Reproduction, 2016)
STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None.
EVALuna2:33464

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer - Hollestelle, Antoinette; Van Der Baan, Frederieke H.; Berchuck, Andrew; Johnatty, Sharon E.; Aben, Katja K.; Agnarsson, Bjarni A.; Aittomaki, Kristiina; Alducci, Elisa; Andrulis, Irene L.; Anton-Culver, Hoda; Antonenkova, Natalia N.; Antoniou, Antonis C.; et al. (Gynecologic Oncology, 2016)
Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370.Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers).We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations.rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
EVALuna2:9251

No Evidence That Genetic Variation in the Myeloid-Derived Suppressor Cell Pathway Influences Ovarian Cancer Survival - Sucheston-Campbell, Lara E.; Cannioto, Rikki; Clay, Alyssa I.; Etter, John Lewis; Eng, Kevin H.; Liu, Song; Battaglia, Sebastiano; Hu, Qiang; Szender, J. Brian; Minlikeeva, Albina; Joseph, Janine M.; Mayor, Paul; et al. (Cancer Epidemiology Biomarkers & Prevention, 2017)
Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses.Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival.Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival.Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes.Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR.
EVALuna2:36152

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing - Easton, Douglas F.; Lesueur, Fabienne; Decker, Brennan; Michailidou, Kyriaki; Li, Jun; Allen, Jamie; Luccarini, Craig; Pooley, Karen A.; Shah, Mitul; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; et al. (Journal of Medical Genetics, 2016)
BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.
EVALuna2:33328

Non-embryo-destructive Extraction of Pluripotent Embryonic Stem Cells: Implications for Regenerative Medicine and Reproductive Medicine - Dittrich, Ralf; Beckmann, Matthias; Wuerfel, W. (Geburtshilfe und Frauenheilkunde, 2015)
On August 1, 2013, the German Patent and Trademark Office issued a patent for the "Non-embryo-destructive extraction of pluripotent embryonic stem cells, stem cells obtained by this process and their uses" (DE 10 2004 062 184 B4). The patent document describes a non-embryo-destructive process to harvest embryonic stem cells from the inner cell mass (ICM) during the blastocyst development stage. The patent application was filed with the German Patent Office in Munich on December 23, 2004 and the patent claim was published in 2006. The patent was granted on August 1, 2013. Processing the patent application was a lengthy affair due to the fact that, for a long time, the prevailing opinion in Germany was that genetic screening of embryos (preimplantation genetic diagnosis) was prohibited under the German Embryo Protection Act (ESchG). A ruling by the German Federal Court in 2010 proved this opinion to be false. Animal studies have provided the evidence that the described procedure is technically feasible; healthy offspring were born after stem cells were harvested from the blastocyst and stored. We report here on a technique for the non-embryo-destructive extraction of pluripotent embryonic stem cells together with potential future applications for stem cells harvested in this manner.
EVALuna2:17552

Novel approach for the assessment of ovarian follicles infiltration in polymeric electrospun patterned scaffolds - Raffel, Nathalie; Dittrich, Ralf; Bäuerle, Tobias; Seyler, Lisa; Amir, Fattahi; Hoffmann, Inge; Leal-Egaña, Aldo; Beckmann, Matthias; Boccaccini, Aldo R.; Liverani, Liliana (PLoS ONE, 2019)
Reproductive tissue engineering (REPROTEN) has been recently defined as the application of the tissue engineering approach targeting reproductive organs and several research works are focusing on this novel strategy. Being still an innovative field, most of the scaffold characterization techniques suitable for other tissue targets give inappropriate results, and there is the need to evaluate and investigate novel approaches. In particular the focus of this paper is the evaluation of the infiltration of ovarian follicles inside patterned electrospun scaffolds. Beyond the standard techniques, for the first time the use of magnetic resonance imaging (MRI) for this purpose is proposed and specific protocols for scaffold preparation are reported. Positive results in terms of evaluation of scaffolds incorporating follicles confirm this technique as highly effective for further applications in this field.
CRIS-Team Scopus Importer:2019-05-17

Novel Associations between Common Breast Cancer Susceptibility Variants and Risk-Predicting Mammographic Density Measures - Stone, Jennifer; Thompson, Deborah J.; Silva, Isabel Dos Santos; Scott, Christopher; Tamimi, Rulla M.; Lindstrom, Sara; Kraft, Peter; Hazra, Aditi; Li, Jingmei; Eriksson, Louise; Czene, Kamila; Hall, Per; et al. (Cancer Research, 2015)
Mammographic density measures adjusted for age and body mass index (BMI) are heritable predictors of breast cancer risk, but few mammographic density-associated genetic variants have been identified. Using data for 10,727 women from two international consortia, we estimated associations between 77 common breast cancer susceptibility variants and absolute dense area, percent dense area and absolute nondense area adjusted for study, age, and BMI using mixed linear modeling. We found strong support for established associations between rs10995190 (in the region of ZNF365), rs2046210 (ESR1), and rs3817198 (LSP1) and adjusted absolute and percent dense areas (all P < 10(-5)). Of 41 recently discovered breast cancer susceptibility variants, associations were found between rs1432679 (EBF1), rs17817449 (MIR1972-2: FTO), rs12710696 (2p24.1), and rs3757318 (ESR1) and adjusted absolute and percent dense areas, respectively. There were associations between rs6001930 (MKL1) and both adjusted absolute dense and nondense areas, and between rs17356907 (NTN4) and adjusted absolute nondense area. Trends in all but two associations were consistent with those for breast cancer risk. Results suggested that 18% of breast cancer susceptibility variants were associated with at least one mammographic density measure. Genetic variants at multiple loci were associated with both breast cancer risk and the mammographic density measures. Further understanding of the underlying mechanisms at these loci could help identify etiologic pathways implicated in how mammographic density predicts breast cancer risk.
EVALuna2:17571

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium - Nagle, C. M.; Dixon, S. C.; Jensen, A.; Kjaer, S. K.; Modugno, F.; Defazio, A.; Fereday, S.; Hung, J.; Johnatty, S. E.; Fasching, Peter; Beckmann, Matthias; Lambrechts, D.; et al. (British Journal of Cancer, 2015)
Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer.We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype.Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ?35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant.Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.
EVALuna2:17568

Occurrence and characteristics of patients with de novo advanced breast cancer according to patient and tumor characteristics – A retrospective analysis of a real world registry - Muller, Volkmar; Hein, Alexander; Hartkopf, Andreas D.; Fasching, Peter; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Häberle, Lothar; Ettl, Johannes; Luftner, Diana; Wallwiener, Markus; Beckmann, Matthias; et al. (European Journal of Cancer, 2022)
Background: Patients with de novo metastatic breast cancer (dnMBC) may have different clinical and pathological characteristics. In studies concerned with first-line metastatic patients, the proportion of these patients without secondary resistance mechanisms may have a large influence ont the study results. The aim of this study was to identify patient and tumor characteristics that are associated with dnMBC vs. recurrent MBC (rMBC). Methods: This is a retrospective analysis of data prospectively collected in the PRAEGNANT metastatic breast cancer registry (NCT02338167). Firs line treated patients were eligible. Patient and tumor characteristics were compared with common disease and tumor characteristics relative to de novo metastatic status, as well as early and late recurrences after primary disease without metastases. Results: Among the 947 patients identified, 355 were included with de novo metastatic disease (37.5%). Older age and HER2-positive disease were significantly associated with a higher frequency of dnMBC. Patients younger than 50, 50–69, or 70 years or older had dnMBC frequencies of 22.7%, 44.0%, and 57.6%, respectively. HER2-positive patients had dnMBC at initial presentation in 49.1% of cases, in comparison with 21.9%, 35.5%, and 37.6% in patients with triple-negative, luminal A–like and luminal B–like breast cancer, respectively. Conclusion: Age and breast cancer subtype are associated with the frequency of first-line MBC patients. Inclusion criteria concerning age or breast cancer subtype can influence the frequency of these patients in a selected patient population and can therefore modify the number of patients with secondary resistance to specific therapies in clinical trials.
CRIS-Team Scopus Importer:2022-07-08
Keywords: Advanced breast cancer; Clinical trials; de novo metastatic breast cancer; Recurrent breast cancer metastases

OLAPARIB IN GERMAN ROUTINE CLINICAL PRACTICE - INTERIM RESULTS OF THE NON-INTERVENTIONAL STUDY C-PATROL - Marme, F.; Sehouli, J.; Welslau, M.; Schinkoethe, T.; El-Balat, A.; Fasching, Peter; Glowik, R.; Hilpert, F. (2017)
EVALuna2:36181

Omics in Seminal Plasma: An Effective Strategy for Predicting Sperm Retrieval Outcome in Non-obstructive Azoospermia - Zarezadeh, Reza; Nikanfar, Saba; Oghbaei, Hajar; Rastgar Rezaei, Yeganeh; Jafari-Gharabaghlou, Davoud; Ahmadi, Yadollah; Nouri, Mohammad; Fattahi, Amir; Dittrich, Ralf (Molecular Diagnosis & Therapy, 2021)
Non-obstructive azoospermia (NOA) is a severe form of male factor infertility resulting from the impairment of sperm production. Surgical sperm retrieval followed by intracytoplasmic sperm injection (ICSI) is the only alternative for NOA patients to have their own genetic children. Nevertheless, due to an approximately 50% chance of success, harvesting sperm from these patients remains challenging. Thus, discovering noninvasive biomarkers, which are able to reliably predict the probability of sperm acquisition, not only can eliminate the risk of surgery but also can lower the costs of NOA diagnosis and treatment. Seminal plasma is the non-cellular and liquid portion of the ejaculate that consists of the secretions originating from testes and male accessory glands. In past years, a wide range of biomolecules including DNAs, RNAs, proteins, and metabolic intermediates have been identified by omics techniques in human seminal plasma. The current review aimed to briefly describe genomic, transcriptomic, proteomic, and metabolomic profiles of human seminal plasma in an attempt to introduce potential candidate noninvasive biomarkers for sperm-retrieval success in men with NOA.
CRIS-Team Scopus Importer:2021-06-11

Oncological heath care networks. The triangle formed by research, quality, and competition - Schrauder, Michael G.; Bamberg, Michael; Beckmann, Matthias (Onkologe, 2016)
The establishment of medical networks has recently gained momentum in health care policy. However, many questions regarding this topic still remain unanswered, including how exactly the terms "supply network" and "network" are defined, and the relevance of such structures in current oncological care in Germany is vague. This manuscript is based on selective literature research in different databases using the search term "networks of medical facilities in oncology". Searching the Internet with the term "supply network" mainly delivers hits related to supply of electricity. Searching for an exact definition of oncological supply networks is largely unfruitful, even when concrete search terms are used. If less vague statements on oncological networks are found, these vary greatly depending on the context. We present an extensive description of the adoption and significance of networking among oncological facilities in the German public health sector. Moreover, the legal requirements as well as future development opportunities of health care services within oncological networks are characterized.
EVALuna2:32990

Operative techniques and complications of extraction and transplantation of ovarian tissue: the Erlangen experience - Beckmann, Matthias; Dittrich, Ralf; Lotz, Laura; Oppelt, Patricia; Findeklee, Sebastian; Hildebrandt, Thomas; Heusinger, Katharina; Cupisti, Susanne; Mueller, Andreas (Archives of Gynecology and Obstetrics, 2017)
PURPOSE: Extracting ovarian tissue before oncologic therapy and transplanting it afterwards are increasingly being used to preserve fertility in women. This study describes standardized and safe operative procedures, with few complications, and reports the resulting ovarian function and pregnancy rates. METHODS: The standardized operative techniques for removing and transplanting ovarian tissue used at the Erlangen center are: for tissue removal, one-third to half of the tissue from one ovary is excised with scissors, without tissue coagulation; for subsequent transplantation, pieces of ovarian tissue are placed in a retroperitoneal pocket without closure of the pocket. RESULTS: Between January 2007 and December 2015, ovarian tissue was extracted in 399 women and transplanted following cancer therapy in 38. No surgical complications were observed within 28 days. To date, there have been ten pregnancies and nine live births after transplantation in seven different women; 26 of the 38 women developed hormonal activity, confirmed by a menstrual cycle or raised serum estradiol levels. CONCLUSIONS: The techniques for laparoscopic removal and transplantation of ovarian tissue described here provide a standardized method with a very low risk of complications. The pregnancy rate after ovarian tissue transplantation, currently 15-30%, can be expected to rise further in the near future.
EVALuna2:36149

Opinion of the German Society of Gynecology and Obstetrics on the Topic - More Knowledge "Risk Factors for Breast Cancer" - Seelbach-Goebel, Birgit; Beckmann, Matthias (Geburtshilfe und Frauenheilkunde, 2017)
EVALuna2:36147

Optimization of Porcine Ovarian Follicle Isolation Methods for Better Developmental Potential - Fattahi, Amir; Liverani, Liliana; Dittrich, Ralf; Hoffmann, Inge; Boccaccini, Aldo R.; Beckmann, Matthias; Bleisinger, Nathalie (Tissue Engineering - Part A, 2020)
In the present study, we present a comparative analysis among the outputs of porcine follicle isolation using either mechanical technique alone or in combination with enzymes, proposing an optimized protocol useful for all further applications related to folliclein vitrogrowth and reproductive tissue engineering. The porcine follicles were isolated using mechanical technique alone (hand blender and scalpels) or in combination with collagenase or Liberase Dispase High (DH) at different doses applying different protocols. Finally, the number, morphology, and stage of isolated follicles were compared between the protocols. Moreover, the follicle viability (live/dead assay) and morphology (rhodamine phalloidin and 4 ',6-diamidino-2-phenylindole staining and scanning electron microscopy analysis) were evaluated after 10 days of culture. We found an optimum protocol for intact follicle isolation using the mechanical technique in combination with enzymes at a concentration of 0.5 mg/mL. However, the number of total isolated follicles and primordial follicles was significantly higher when collagenase was used compared to Liberase DH (p < 0.05), while Liberase DH could isolate a significantly higher percentage of preantral follicles. After 10 days of culture, the morphology and health status of follicles were statistically higher when Liberase DH was used in comparison with collagenase. Moreover, on the follicles extracted with Liberase DH, it was possible to observe theca cells covering part of the follicle surface. In conclusion, we demonstrated that the intact primary or secondary follicles could not be obtained using only mechanical methods, which led to the isolation of denuded oocytes and dramatically damaged follicles. We concluded that the collagenase-based follicle isolation could negatively affect the morphology and developmental potential of the follicles. Moreover, the incubation of ovarian cortex tissues with Liberase DH solution is an optimized protocol for porcine ovarian follicle isolation with developmental competence.
CRIS-Team WoS Importer:2020-07-24

Optimizing R with SparkR on a commodity cluster for biomedical research - Sedlmayr, Martin; Würfl, Tobias; Maier, Christian; Haeberle, Lothar; Fasching, Peter; Prokosch, Hans-Ulrich; Christoph, Jan (Computer Methods and Programs in Biomedicine, 2016)
Medical researchers are challenged today by the enormous amount of data collected in healthcare. Analysis methods such as genome-wide association studies (GWAS) are often computationally intensive and thus require enormous resources to be performed in a reasonable amount of time. While dedicated clusters and public clouds may deliver the desired performance, their use requires upfront financial efforts or anonymous data, which is often not possible for preliminary or occasional tasks. We explored the possibilities to build a private, flexible cluster for processing scripts in R based on commodity, non-dedicated hardware of our department.For this, a GWAS-calculation in R on a single desktop computer, a Message Passing Interface (MPI)-cluster, and a SparkR-cluster were compared with regards to the performance, scalability, quality, and simplicity.The original script had a projected runtime of three years on a single desktop computer. Optimizing the script in R already yielded a significant reduction in computing time (2 weeks). By using R-MPI and SparkR, we were able to parallelize the computation and reduce the time to less than three hours (2.6 h) on already available, standard office computers. While MPI is a proven approach in high-performance clusters, it requires rather static, dedicated nodes. SparkR and its Hadoop siblings allow for a dynamic, elastic environment with automated failure handling. SparkR also scales better with the number of nodes in the cluster than MPI due to optimized data communication.R is a popular environment for clinical data analysis. The new SparkR solution offers elastic resources and allows supporting big data analysis using R even on non-dedicated resources with minimal change to the original code. To unleash the full potential, additional efforts should be invested to customize and improve the algorithms, especially with regards to data distribution.
EVALuna2:174

Orofacial clefts alter early life oral microbiome maturation towards higher levels of potentially pathogenic species: A prospective observational study - Seidel, Corinna L.; Strobel, Karin; Weider, Matthias; Tschaftari, Marco; Unertl, Christoph; Willershausen, Ines; Weber, Manuel; Hörning, André; Morhart, Patrick; Schneider, Michael; Beckmann, Matthias; Bogdan, Christian; et al. (Journal of Oral Microbiology, 2023)
Orofacial clefts (OFC) present different phenotypes with a postnatal challenge for oral microbiota development. In order to investigate the impact of OFC on oral microbiota, smear samples from 15 neonates with OFC and 17 neonates without OFC were collected from two oral niches (tongue, cheek) at two time points, i.e. after birth (T0: Ø3d OFC group; Ø2d control group) and 4–5 weeks later (T1: Ø32d OFC group; Ø31d control group). Subsequently, the samples were analyzed using next-generation sequencing. We detected a significant increase of alpha diversity and anaerobic and Gram-negative species from T0 to T1 in both groups. Further, we found that at T1 OFC neonates presented a significantly lower alpha diversity (lowest values for high cleft severity) and significantly higher levels of Enterobacteriaceae (Citrobacter, Enterobacter, Escherichia-Shigella, Klebsiella), Enterococcus, Bifidobacterium, Corynebacterium, Lactocaseibacillus, Staphylococcus, Acinetobacter and Lawsonella compared to controls. Notably, neonates with unilateral and bilateral cleft lip and palate (UCLP/BCLP) presented similarities in beta diversity and a mixture with skin microbiota. However, significant differences were seen in neonates with cleft palate only compared to UCLP/BCLP with higher levels of anaerobic species. Our findings revealed an influence of OFC as well as cleft phenotype and severity on postnatal oral microbiota maturation.
CRIS-Team Scopus Importer:2023-01-20
Keywords: early life dysbiosis; microbiome maturation; neonates; oral microbiome; Orofacial clefts

Orofacial clefts lead to increased pro-inflammatory cytokine levels on neonatal oral mucosa - Seidel, Corinna L.; Percivalle, Elena; Tschaftari, Marco; Weider, Matthias; Strobel, Karin; Willershausen, Ines; Unertl, Christoph; Schmetzer, Helga M.; Weber, Manuel; Schneider, Michael; Frey, Benjamin; Gaipl, Udo; et al. (Frontiers in Immunology, 2022)
Orofacial clefts (OFC) are frequent congenital malformations characterized by insufficient separation of oral and nasal cavities and require presurgical infant orthopedics and surgical interventions within the first year of life. Wound healing disorders and higher prevalence of gingivitis and plaque levels are well-known challenges in treatment of children with OFC. However, oral inflammatory mediators were not investigated after birth using non-invasive sampling methods so far. In order to investigate the impact of OFC on oral cytokine levels, we collected tongue smear samples from 15 neonates with OFC and 17 control neonates at two time points (T), T0 at first consultation after birth, and T1, 4 to 5 weeks later. The samples were analyzed using multiplex immunoassay. Overall, we found significantly increased cytokine levels (TNF, IL-1β/-2/-6/-8/-10) in tongue smear samples from neonates with OFC compared to controls, especially at T0. The increase was even more pronounced in neonates with a higher cleft severity. Further, we detected a significant positive correlation between cleft severity score and distinct pro-inflammatory mediators (GM-CSF, IL-1β, IL-6, IL-8) at T0. Further, we found that breast-milk (bottle) feeding was associated with lower levels of pro-inflammatory cytokines (IL-6/-8) in neonates with OFC compared to formula-fed neonates. Our study demonstrated that neonates with OFC, especially with high cleft severity, are characterized by markedly increased inflammatory mediators in tongue smear samples within the first weeks of life potentially presenting a risk for oral inflammatory diseases. Therefore, an inflammatory monitoring of neonates with (severe) OFC and the encouragement of mother to breast-milk (bottle) feed might be advisable after birth and/or prior to cleft surgery.
CRIS-Team Scopus Importer:2022-12-16
Keywords: cleft lip and palate; cytokines; mucosal homeostasis; mucosal immunity; neonates; oral; oral inflammation; orofacial clefts

Outcome after neoadjuvant chemotherapy in elderly breast cancer patients - a pooled analysis of individual patient data from eight prospectively randomized controlled trials - von Waldenfels, Gabriel; Loibl, Sibylle; Furlanetto, Jenny; Machleidt, Anna; Lederer, Bianca; Denkert, Carsten; Hanusch, Claus; Kümmel, Sherko; von Minckwitz, Gunter; Schneeweiss, Andreas; Untch, Michael; Rhiem, Kerstin; et al. (Oncotarget, 2018)
Introduction: Recent studies showed the high and independent impact of age (<40 years) on pathologic complete response (pCR) and prognosis for patients undergoing neoadjuvant chemotherapy (NACT). Some physicians might not consider elderly patients (>65 years) for NACT due to poor prognosis or higher toxicity. The aim of this analysis is to help selecting appropriately elderly women who would benefit from NACT. Secondly, survival parameters are investigated in several histological subgroups. Methods: From 1998 to 2010, eight prospectively randomized German Breast Group (GBG) trials of anthracycline- and taxane-based NACT were performed and analyzed in this study. Results: Compared to the overall average, elderly women had significant larger tumors and more overall lymph node involvement. Histologically, they had more G2 tumors, more estrogen-receptor positive tumors. pCR (ypT0 ypN0) was strongly associated with age. The multivariable logistic regression analysis of clinical parameters showed that young age, clinical stage T4, invasive ductal cancer and poor differentiated breast cancer are predictive for high pCR. The multivariate analyses of molecular subgroups showed that age >65years is a predictor of significant lower pCR in HER2- breast cancers. Nonetheless, HER2+ patients showed pCR rates as high- and HR+/HER2+ even higher - pCR rates compared to younger patients. Discussion: This study underlines the unfavorable impact of higher age on pCR, but it shows a realistic chance for pCR if NACT is applied - especially for HER2+ patients. Furthermore, elderly patients with non-TNBC showed a good prognosis (comparable to younger patients) regarding overall survival, even if they do not have pCR.
EVALuna2:210017

Outcome after neoadjuvant chemotherapy in estrogen receptor-positive and progesterone receptor-negative breast cancer patients: a pooled analysis of individual patient data from ten prospectively randomized controlled neoadjuvant trials - Van Mackelenbergh, Marion T.; Denkert, Carsten; Nekljudova, Valentina; Karn, Thomas; Schem, Christian; Marme, Frederik; Stickeler, Elmar; Jackisch, Christian; Hanusch, Claus; Huober, Jens; Fasching, Peter; Blohmer, Jens-Uwe; et al. (Breast Cancer Research and Treatment, 2018)
The estrogen receptor (ER) is involved in control of progesterone receptor (PgR) expression and lack of PgR may be also a surrogate of altered growth factor signaling. The aim of this study was therefore to investigate PgR expression as predictive factor for response to neoadjuvant therapy and long-term outcome.Five thousand and six hundred and thirteen patients with primary breast cancer and positive ER expression from ten German neoadjuvant trials of anthracycline and taxane-based chemotherapy were included. Pathologic complete response (pCR), disease-free survival (DFS), distant disease-free survival (DDFS), overall survival (OS), and local recurrence-free survival (LRFS) were compared according to PgR expression.The lack of PgR expression (1172 patients) was associated with grade 3 (38.4 vs. 26.3%; p < 0.001), nodal involvement (>cN2) (6.8% vs. 4.7%; p = 0.004), and HER2 positivity (36.2 vs. 22.3%; p < 0.001). pCR rates of PgR-negative tumors were higher in the entire cohort (13.8 vs. 7.5%; p < 0.001) and in the HER2-negative subgroup (11.2 vs. 5.8%; p < 0.001). In multivariable logistic regression, PgR negativity was an independent predictive factor for pCR overall (OR 1.76; p < 0.001) and in the HER2-negative patients (OR 1.99; p < 0.001). Patients with PgR-negative disease had significantly worse outcome (p < 0.001, respectively). Multivariable Cox regression analysis revealed that PgR was an independent prognostic factor for DFS, OS, DDFS, and LRFS.ER-positive/PgR-negative breast carcinomas are associated with higher response but also worse long-term outcome after neoadjuvant therapy. PgR negativity is an independent predictive factor for pCR after neoadjuvant chemotherapy in ER-positive HER2-negative breast cancer.
EVALuna2:56119

Outcome and prognosis in uterine sarcoma and malignant mixed Mullerian tumor - Burghaus, Stefanie; Halmen, Sonja; Gaß, Paul; Mehlhorn, Grit; Schrauder, Michael G.; Lux, Michael P.; Renner, Stefan; Beckmann, Matthias; Hein, Alexander; Thiel, Falk (Archives of Gynecology and Obstetrics, 2016)
PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.
EVALuna2:32968

Ovarian function in young patients (pts) treated with postneoadjuvant palbociclib (PAL) and endocrine therapy (ET) for hormone receptor (HR)-positive, HER2-negative early breast cancer (BC): Explorative analysis in Penelope-B - Furlanetto, J.; Marme, F.; Thode, C.; Nekljudova, V.; Liu, Y.; Jimenez, M. Martin; Reimer, T.; Knudsen, E.; Denkert, C.; Bassy, M.; Martin, L-A.; Karn, T.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Ovarian tissue cryopreservation and retransplantation–what do patients think about it? - Lotz, Laura; Maktabi, Amina; Hoffmann, Inge; Findeklee, Sebastian; Beckmann, Matthias; Dittrich, Ralf (Reproductive Biomedicine Online, 2016)
Cryopreservation of ovarian tissue has been successfully applied clinically, with over 60 live births to date. The aim of the present study was to perform a survey of patients who have had ovarian tissue cryopreserved in the Department of Obstetrics and Gynecology, Erlangen University Hospital, in order to obtain information about: why patients opt for fertility preservation; their current fertility; pregnancy attempts and outcomes; and their intended plans for the cryopreserved ovarian tissue. In total, 147 women took part in the survey (average age 25.0 ± 7.0 years; response rate 48%; mean follow-up period 6 years). Sixty-six reported regular menstrual cycles; 48 were amenorrhoeic. Sixty-two women had tried to conceive; 33 reported pregnancies. Twenty-five had delivered healthy children after conceiving naturally; eight had conceived with assisted reproduction. Five patients had had their ovarian tissue retransplanted. Although many patients continued to have ovarian function, none of them regretted choosing cryopreservation of ovarian tissue. Cryopreservation of ovarian tissue is an effective option and is very important for women diagnosed with cancer. Analyses of the clinical outcomes in these patients are essential in order to identify those patients capable of benefiting most from the procedure and in order to improve the technique.
EVALuna2:32986

Ovarian Tissue Transplantation: Experience From Germany and Worldwide Efficacy - Lotz, Laura; Dittrich, Ralf; Hoffmann, Inge; Beckmann, Matthias (Clinical Medicine Insights: Reproductive Health, 2019)
Extraction of ovarian tissue prior to oncologic therapy and subsequent transplantation is being performed increasingly often to preserve fertility in women. The procedure can be performed at any time of the cycle and, therefore, generally does not lead to any delay in oncological therapy. Success rates with transplantation of cryopreserved ovarian tissue have reached promising levels. More than 130 live births have been reported worldwide with the aid of cryopreserved ovarian tissue and the estimated birth rate is currently approximately 30%. In Germany, Austria, and Switzerland, the FertiPROTEKT consortium has successfully achieved 21 pregnancies and 17 deliveries generated after 95 ovarian tissue transplantations by 2015, one of the largest case series worldwide confirming that ovarian tissue cryopreservation and transplantation are successful. Approximately, more than 400 ovarian tissue cryopreservation procedures are performed each year in the FertiPROTEKT consortium. and the request and operations for ovarian tissue transplantation have increased in recent years. Therefore. recommendations for managing transplantation of ovarian tissue to German-speaking reproductive medicine centers were developed. In this overview. these recommendations and our experience in ovarian tissue transplantation are presented and discussed with international procedures.
CRIS-Team WoS Importer:2019-10-22

Ovarian tissue transplantations in 196 women by FertiPROTEKT- live birth rate of 26.5% per woman is associated with female age and first versus repeated transplantation - Lotz, Laura; Bender-Liebenthron, J.; Dittrich, Ralf; Häberle, Lothar; Beckmann, Matthias; Germeyer, A.; Korell, M.; Saenger, N.; Von Wolff, M. (HUMAN REPRODUCTION, 2022)
CRIS-Team WoS Importer:2022-10-21

Overall survival (OS) results of the phase III MONALEESA-3 trial of postmenopausal patients (pts) with hormone receptor-positive (HR plus ), human epidermal growth factor 2-negative (HER2-) advanced breast cancer (ABC) treated with fulvestrant (FUL) (+) ribociclib (RIB) - Slamon, D. J.; Neven, P.; Chia, S.; Fasching, Peter; De Laurentiis, M.; Im, S-A.; Petrakova, K.; Bianchi, G. V.; Esteva, F. J.; Martin, M.; Nusch, A.; Sonke, G. S.; et al. (ANNALS OF ONCOLOGY, 2019)
CRIS-Team WoS Importer:2019-11-08

Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer - Slamon, Dennis J.; Neven, Patrick; Chia, Stephen; Fasching, Peter; De Laurentiis, Michelino; Im, Seock-Ah; Petrakova, Katarina; Bianchi, Giulia V.; Esteva, Francisco J.; Martin, Miguel; Nusch, Arnd; Sonke, Gabe S.; et al. (New England Journal of Medicine, 2020)
BACKGROUND In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor positive, human epidermal growth factor receptor 2 (HER2) negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival. METHODS Patients were randomly assigned in a 2;1 ratio to receive either ribociclib or placebo in addition to fulvestrant as first-line or second-line treatment. Survival was evaluated by means of a stratified log-rank test and summarized with the use of Kaplan Meier methods. RES U ITS This analysis was based on 275 deaths: 167 among 484 patients (34.5%) receiving ribociclib and 108 among 242 (44.6 /o) receiving placebo. Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant. The estimated overall survival at 42 months was 57.8% (95% confidence interval [CI], 52.0 to 63.2) in the ribociclib group and 45.9% (95% CI, 36.9 to 54.5) in the placebo group, for a 28 /0 difference in the relative risk of death (hazard ratio, 0.72; 95% Cl, 0.57 to 0.92; P=0.00455). The benefit was consistent across most subgroups. In a descriptive update, median progression-free survival among patients receiving first-line treatment was 33.6 months (95% CI, 27.1 to 41.3) in the ribociclib group and 19.2 months (95% Cl, 14.9 to 23.6) in the placebo group. No new safety signals were observed. CONCLUSIONS Ribociclib plus fulvestrant showed a significant overall survival benefit over placebo plus fulvestrant in patients with hormone-receptor positive, HER2-negative advanced breast cancer. (Funded by Novartis; MONALEESA-3 ClinicalTrials.gov number, NCT02422615.)
CRIS-Team WoS Importer:2020-02-21

Oxytocin receptor DNA methylation in postpartum depression - Kimmel, Mary; Clive, Makena; Gispen, Fiona; Guintivano, Jerry; Brown, Tori; Cox, Olivia; Beckmann, Matthias; Kornhuber, Johannes; Fasching, Peter; Osborne, Lauren M.; Binder, Elisabeth; Payne, Jennifer L.; et al. (Psychoneuroendocrinology, 2016)
The oxytocin receptor (OXTR) is a key regulator of stress and anxiety and may be regulated by both psychosocial risk factors and gonadal hormones, making it an attractive candidate for study in postpartum depression (PPD). The objective of this study was to investigate both serum hormone and PPD specific DNA methylation variation in the OXTR. Illumina HM450 microarray data generated in a prospective PPD cohort identified significant associations (P=0.014) with PPD in an intronic region in the OXTR located 4bp proximal to an estrogen receptor (ER) binding region. Pyrosequencing confirmed moderate evidence for an interaction of CpGs in the region with childhood abuse status to mediate PPD. These CpGs located on chr3 at positions 8810078 and 8810069 exhibited significant associations with postpartum depression scores from an independent cohort of 240 women with no prior psychiatric history. Hormone analysis suggested a PPD specific negative correlation of DNA methylation in the region with serum estradiol levels. Estradiol levels and OXTR DNA methylation exhibited a significant interaction to associate with the ratio of allopregnanolone to progesterone. Cumulatively, the data corroborate our previous hypotheses of a PPD specific increased sensitivity of epigenetic reprogramming at estrogen target genes and suggests that OXTR epigenetic variation may be an important mediator of mood relevant neuroactive steroid production.
EVALuna2:23775

p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group - Woelber, Linn; Prieske, Katharina; Eulenburg, Christine; Oliveira-Ferrer, Leticia; de Gregorio, Nikolaus; Klapdor, Ruediger; Kalder, Matthias; Braicu, Iona; Fuerst, Sophie; Klar, Maximilian; Strauss, Hans Georg; Beckmann, Matthias; et al. (American Journal of Obstetrics and Gynecology, 2021)
Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma—a human papillomavirus–dependent pathway characterized by p16 overexpression and a human papillomavirus–independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed. Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance. Study Design: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction. Results: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53− (n=132), and p16−/p53− (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53− tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16−/p53− tumors; P<.0001) and showed lower rates of lymph-node involvement (28.0% vs 42.3% for p53+, respectively, 30.2% for p16−/p53− tumors; P=.050). Notably, 2-year-disease-free and overall survival rates were significantly different among the groups: disease-free survival, 47.1% (p53+), 60.2% (p16−/p53−), and 63.9% (p16+/p53−) (P<.001); overall survival, 70.4% (p53+), 75.4% (p16−/p53−), and 82.5% (p16+/p53−) (P=.002). In multivariate analysis, the p16+/p53− phenotype showed a consistently improved prognosis compared with the other groups (hazard ratio, 0.66; 95% confidence interval, 0.44–0.99; P=.042). Conclusion: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53−/p16− phenotype showing an intermediate prognosis that needs to be further characterized.
CRIS-Team Scopus Importer:2021-04-09
Keywords: HPV; p16; p53; prognosis; vulvar cancer

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS - Southey, Melissa C.; Goldgar, David E.; Winqvist, Robert; Pylkas, Katri; Couch, Fergus; Tischkowitz, Marc; Foulkes, William D.; Dennis, Joe; Michailidou, Kyriaki; Van Rensburg, Elizabeth J.; Heikkinen, Tuomas; Nevanlinna, Heli; et al. (Journal of Medical Genetics, 2016)
The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.We genotyped 10 rare mutations using the custom iCOGS array: PALB2 c.1592delT, c.2816T>G and c.3113G>A, CHEK2 c.349A>G, c.538C>T, c.715G>A, c.1036C>T, c.1312G>T, and c.1343T>G and ATM c.7271T>G. We assessed associations with breast cancer risk (42 671 cases and 42 164 controls), as well as prostate (22 301 cases and 22 320 controls) and ovarian (14 542 cases and 23 491 controls) cancer risk, for each variant.For European women, strong evidence of association with breast cancer risk was observed for PALB2 c.1592delT OR 3.44 (95% CI 1.39 to 8.52, p=7.1×10(-5)), PALB2 c.3113G>A OR 4.21 (95% CI 1.84 to 9.60, p=6.9×10(-8)) and ATM c.7271T>G OR 11.0 (95% CI 1.42 to 85.7, p=0.0012). We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p<=0.017). Evidence for prostate cancer risk was observed for CHEK2 c.1343T>G OR 3.03 (95% CI 1.53 to 6.03, p=0.0006) for African men and CHEK2 c.1312G>T OR 2.21 (95% CI 1.06 to 4.63, p=0.030) for European men. No evidence of association with ovarian cancer was found for any of these variants.This report adds to accumulating evidence that at least some variants in these genes are associated with an increased risk of breast cancer that is clinically important.
EVALuna2:6832

Palliative therapy concepts for pancreatic carcinoma - Brunner, Michaela; Grützmann, Robert; Weber, Georg (Chirurg, 2018)
The majority of patients with ductal pancreatic adenocarcinoma are already in a locally advanced or metastatic stage at the time of diagnosis and require palliative therapy. Interventional and operative measures are available for the restoration of biliary outflow in bile duct obstruction and the continuity of the upper intestinal lumen in duodenal or gastric outlet obstruction. In the presence of tumor-related pain, pain therapy according to the World Health Organization (WHO) scheme or a truncus coeliacus blockade, in cachexia a nutritional therapy and in thromboembolic events an anticoagulant therapy are used. An individualized palliative chemotherapy regimen should be selected for each patient, taking into account the patient's general condition and the side effects profile of the chemotherapeutic agents. Radiochemotherapy and local ablative therapies should currently only be used within the framework of studies. A palliative resection is not recommended according to current knowledge.
EVALuna2:212624

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche - Perry, John R. B.; Day, Felix; Elks, Cathy E.; Sulem, Patrick; Thompson, Deborah J.; Ferreira, Teresa; He, Chunyan; Chasman, Daniel I.; Esko, Toenu; Thorleifsson, Gudmar; Albrecht, Eva; Ang, Wei Q.; et al. (Nature, 2014)
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and ?-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
EVALuna2:17437

Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis - Cortazar, Patricia; Zhang, Lijun; Untch, Michael; Mehta, Keyur; Costantino, Joseph P.; Wolmark, Norman; Bonnefoi, Herve; Cameron, David; Gianni, Luca; Valagussa, Pinuccia; Swain, Sandra M.; Prowell, Tatiana; et al. (Lancet, 2014)
Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS.We searched PubMed, Embase, and Medline for clinical trials of neoadjuvant treatment of breast cancer. To be eligible, studies had to meet three inclusion criteria: include at least 200 patients with primary breast cancer treated with preoperative chemotherapy followed by surgery; have available data for pathological complete response, EFS, and OS; and have a median follow-up of at least 3 years. We compared the three most commonly used definitions of pathological complete response–ypT0 ypN0, ypT0/is ypN0, and ypT0/is–for their association with EFS and OS in a responder analysis. We assessed the association between pathological complete response and EFS and OS in various subgroups. Finally, we did a trial-level analysis to assess whether pathological complete response could be used as a surrogate endpoint for EFS or OS.We obtained data from 12 identified international trials and 11 955 patients were included in our responder analysis. Eradication of tumour from both breast and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) was better associated with improved EFS (ypT0 ypN0: hazard ratio [HR] 0·44, 95% CI 0·39-0·51; ypT0/is ypN0: 0·48, 0·43-0·54) and OS (0·36, 0·30-0·44; 0·36, 0·31-0·42) than was tumour eradication from the breast alone (ypT0/is; EFS: HR 0·60, 95% CI 0·55-0·66; OS 0·51, 0·45-0·58). We used the ypT0/is ypN0 definition for all subsequent analyses. The association between pathological complete response and long-term outcomes was strongest in patients with triple-negative breast cancer (EFS: HR 0·24, 95% CI 0·18-0·33; OS: 0·16, 0·11-0·25) and in those with HER2-positive, hormone-receptor-negative tumours who received trastuzumab (EFS: 0·15, 0·09-0·27; OS: 0·08, 0·03, 0·22). In the trial-level analysis, we recorded little association between increases in frequency of pathological complete response and EFS (R(2)=0·03, 95% CI 0·00-0·25) and OS (R(2)=0·24, 0·00-0·70).Patients who attain pathological complete response defined as ypT0 ypN0 or ypT0/is ypN0 have improved survival. The prognostic value is greatest in aggressive tumour subtypes. Our pooled analysis could not validate pathological complete response as a surrogate endpoint for improved EFS and OS.US Food and Drug Administration.
EVALuna2:17518

Pathological Response in the Breast and Axillary Lymph Nodes after Neoadjuvant Systemic Treatment in Patients with Initially Node-Positive Breast Cancer Correlates with Disease Free Survival: An Exploratory Analysis of the GeparOcto Trial - Gerber, Bernd; Schneeweiss, Andreas; Möbus, Volker; Golatta, Michael; Tesch, Hans; Krug, David; Hanusch, Claus; Denkert, Carsten; Lübbe, Kristina; Heil, Jörg; Huober, Jens; Ataseven, Beyhan; et al. (Cancers, 2022)
Background: The conversion of initially histologically confirmed axillary lymph node-positive (pN+) to ypN0 after neoadjuvant systemic treatment (NAST) is an important prognostic factor in breast cancer (BC) patients and may influence surgical de-escalation strategies. We aimed to determine pCR rates in lymph nodes (pCR-LN), the breast (pCR-B), and both (tpCR) in women who present with pN+ BC, to assess predictors for response and the impact of pCR-LN, pCR-B, and tpCR on invasive disease-free survival (iDFS). Methods: Retrospective, exploratory analysis of 242 patients with pN+ at diagnosis from the multicentric, randomized GeparOcto trial. Results: Of 242 patients with initially pN+ disease, 134 (55.4%) had a pCR-LN, and 109 (45.0%) a pCR-B. Of the 109 pCR-B patients, 9 (8.3%) patients had involved LN, and 100 (41.3%) patients had tpCR. Those with involved LN still had a bad prognosis. As expected, pCR-B and intrinsic subtypes (TNBC and HER2+) were identified as independent predictors of pCR-LN. pCR-LN (ypN0; hazard ratio 0.42; 95%, CI 0.23–0.75; p = 0.0028 for iDFS) was the strongest independent prognostic factor. Conclusions: In initially pN+ patients undergoing NAST, the conversion to ypN0 is of high prognostic value. Surgical axillary staging after NAST is still essential in these patients to offer tailored treatment.
CRIS-Team Scopus Importer:2022-01-28
Keywords: Axillary surgery; Breast cancer; Lymph node; Neoadjuvant therapy; Pathological complete response; Prognosis

Pathology of Tumors Associated With Pathogenic Germline Variants in 9 Breast Cancer Susceptibility Genes - Mavaddat, Nasim; Dorling, Leila; Carvalho, Sara; Allen, Jamie; Gonzalez-Neira, Anna; Keeman, Renske; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Ahearn, Thomas U.; Andrulis, Irene L.; Beckmann, Matthias; et al. (JAMA Oncology, 2022)
IMPORTANCE Rare germline genetic variants in several genes are associated with increased breast cancer (BC) risk, but their precise contributions to different disease subtypes are unclear. This information is relevant to guidelines for gene panel testing and risk prediction.
CRIS-Team WoS Importer:2022-02-11

Pathway-Based Analysis of Genome-Wide Association Data Identified SNPs in as Biomarker for Chemotherapy- Induced Neutropenia in Breast Cancer Patients - Bidadi, Behzad; Liu, Duan; Kalari, Krishna R.; Rübner, Matthias; Hein, Alexander; Beckmann, Matthias; Rack, Brigitte; Janni, Wolfgang; Fasching, Peter; Weinshilboum, Richard M.; Wang, Liewei (Frontiers in Pharmacology, 2018)
Neutropenia secondary to chemotherapy in breast cancer patients can be life-threatening and there are no biomarkers available to predict the risk of drug-induced neutropenia in those patients. We previously performed a genome-wide association study (GWAS) for neutropenia events in women with breast cancer who were treated with 5-fluorouracil, epirubicin and cyclophosphamide and recruited to the SUCCESS-A trial. A genome-wide significant single-nucleotide polymorphism (SNP) signal in the tumor necrosis factor superfamily member 13B () gene, encoding the cytokine B-cell activating factor (BAFF), was identified in that GWAS. Taking advantage of these existing GWAS data, in the present study we utilized a pathway-based analysis approach by leveraging knowledge of the pharmacokinetics and pharmacodynamics of drugs and breast cancer pathophysiology to identify additional SNPs/genes associated with the underlying etiology of chemotherapy-induced neutropenia. We identified three SNPs in the hyaluronan mediated motility receptor ( gene that were significantly associated with neutropenia ( < 1.0E-04). Those three SNPs were trans-expression quantitative trait loci for the expression of ( < 1.0E-04). The minor allele of these SNPs was associated with a decreased mRNA level. Additional functional studies performed with lymphoblastoid cell lines (LCLs) demonstrated that LCLs possessing the minor allele for the SNPs were more sensitive to drug treatment. Knock-down of in LCLs and HL-60 promyelocytic cells and treatment of those cells with BAFF modulated the cell sensitivity to chemotherapy treatment. These results demonstrate that SNP-dependent cytotoxicity of these chemotherapeutic agents might be related to expression level. In summary, utilizing a pathway-based approach for the analysis of GWAS data, we identified additional SNPs in the gene that were associated with neutropenia and also were correlated with expression.
EVALuna2:56169

Patient quality of life (QoL) from the GeparX trial on the addition of denosumab (Dmab) added to two different nab-paclitaxel (nP) regimens as neoadjuvant chemotherapy (NACT) in primary breast cancer (BC) - Reinisch, M.; Blohmer, J-U.; Link, T.; Just, M.; Untch, M.; Stoetzer, O.; Fasching, Peter; Schneeweiss, A.; Wimberger, P.; Seiler, S.; Huober, J.; Thill, M.; et al. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Patient-reported outcomes and hospitalization data in patients with HER2-positive metastatic breast cancer receiving trastuzumab deruxtecan or trastuzumab emtansine in the phase III DESTINY-Breast03 study - Curigliano, G.; Dunton, K.; Rosenlund, M.; Janek, M.; Cathcart, J.; Liu, Y.; Fasching, Peter; Iwata, H. (Annals of Oncology, 2023)
Background: In the DESTINY-Breast03 clinical trial, trastuzumab deruxtecan (T-DXd) showed superior progression-free survival and overall survival versus trastuzumab emtansine (T-DM1) and manageable safety in patients with human epidermal growth factor receptor 2 (HER2)-positive (HER2+) metastatic breast cancer. Here, patient-reported outcomes (PROs) are reported along with hospitalization data. Patients and methods: Patients in DESTINY-Breast03 were assessed for prespecified PRO measures, including European Organization for Research and Treatment of Cancer quality of life (EORTC-QoL) questionnaires [the oncology-specific EORTC Quality of Life Questionnaire Core 30 (QLQ-C30) and breast cancer-specific EORTC QLQ-BR45] and the generic EuroQol 5-dimension 5-level questionnaire (EQ-5D-5L) visual analogue scale. Analyses included change from baseline, time to definitive deterioration (TDD), and hospitalization-related endpoints. Results: EORTC QLQ-C30 baseline global health status (GHS) scores for T-DXd (n = 253) and T-DM1 (n = 260) were similar, with no clinically meaningful change (<10-point change from baseline) while on either treatment (median treatment duration: T-DXd, 14.3 months; T-DM1, 6.9 months). TDD analyses of QLQ-C30 GHS (primary PRO variable) and all other prespecified PROs (QLQ-C30 subscales, the QLQ-BR45 arm symptoms scale, and the EQ-5D-5L visual analogue scale) suggested T-DXd was numerically favored over T-DM1 based on TDD hazard ratios. Of all randomized patients, 18 (6.9%) receiving T-DXd versus 19 (7.2%) receiving T-DM1 were hospitalized, and the median time to first hospitalization was 219.5 versus 60.0 days, respectively. Conclusions: In DESTINY-Breast03, EORTC GHS/QoL was maintained on both therapies throughout treatment, indicating that despite the longer treatment duration with T-DXd versus T-DM1, health-related QoL did not worsen on T-DXd. Furthermore, TDD hazard ratios numerically favored T-DXd over T-DM1 in all prespecified variables of interest including pain, suggesting T-DXd may delay time until health-related QoL deterioration compared with T-DM1. Median time to first hospitalization was three times longer with T-DXd versus T-DM1. Together with reported improved efficacy and manageable toxicity, these results support the overall benefit of T-DXd for patients with HER2+ metastatic breast cancer.
CRIS-Team Scopus Importer:2023-06-30
Keywords: breast cancer; hospitalization; quality of life; trastuzumab deruxtecan; trastuzumab emtansine

Patient-reported outcomes (PRO) focused on adverse events (PRO-AEs) in adjuvant and metastatic breast cancer: clinical and translational implications - Stefanovic, Stefan; Wallwiener, Markus; Karic, Uros; Domschke, Christoph; Katic, Luka; Taran, Florin-Andrei; Pesic, Aleksandra; Hartkopf, Andreas; Hadji, Peyman; Teufel, Martin; Schuetz, Florian; Sohn, Christof; et al. (Supportive Care in Cancer, 2017)
PURPOSE: The capture of adequate treatment outcomes and quality of life (QOL) of advanced breast cancer patients in clinical routine represents a great challenge. Patient-reported outcomes (PROs) are data elements directly reported by patients about experiences with care, including symptoms, functional status, or quality of life. There is growing interest in the medical community for the evaluation and implementation of PROs of adverse events (PRO-AEs). Recent interest in PROs in health care has evolved in the context of patient centeredness. Our primary objective was to identify trials that had implemented PRO-AEs in the breast cancer treatment setting, thereby demonstrating its feasibility. We aimed to identify published studies that used patient reports to assess AEs during and after breast cancer treatment, to identify clinician underreported and modifiable AEs that are important to patients, and to analyze the feasibility and usefulness of PRO instrument implementation in everyday oncological practice with special attention given to electronic-based PRO instruments. METHODS: We conducted a systematic search of PubMed for studies that used PRO instruments to assess AEs of breast cancer treatment in the metastatic and adjuvant settings. Two authors independently reviewed the search results and decided which studies fully met the predefined inclusion criteria. RESULTS: The search yielded 606 publications. The two reviewers found that 9 studies met the inclusion criteria. Three AEs were identified as important to patients but inadequately reported by health care providers, namely hot flushes, vaginal dryness, and weight gain. CONCLUSIONS: PROs and PRO-AEs are the consequence of contemporary concepts of patient-centered medicine and the growing feasibility, utility, and implications of collecting data using modern technology. Furthermore, the willingness of patients to utilize innovative applications for their own health has been increasing in parallel to the enhanced impact of the World Wide Web. Especially, the coverage of the metastatic situation promises numerous findings on the structure and quality of health care, enabling implementation of individually tailored interventions. Remote electronic self-reporting (i.e., home reporting) is feasible and is associated with high compliance levels.
EVALuna2:36208

Patient-reported outcomes (PROs) from DESTINY-Breast03, a randomized phase III study of trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (MBC) - Curigliano, G.; Dunton, K.; Rosenlund, M.; Janek, M.; Cathcart, J.; Liu, Y.; Fasching, Peter; Iwata, H. (ANNALS OF ONCOLOGY, 2022)
CRIS-Team WoS Importer:2022-06-03

Patient-reported outcomes (PROs) in advanced breast cancer (ABC) treated with ribociclib plus fulvestrant: Results from MONALEESA-3 - Fasching, Peter; Esteva, F. J.; Pivot, X.; Nusch, A.; Beck, J. T.; Chan, A.; Pieris-Gunatilaka, A.; Wang, Y.; Lanoue, B.; Chandiwana, D.; Neven, P. (ANNALS OF ONCOLOGY, 2018)
CRIS-Team WoS Importer:2019-03-08

Patient-reported outcomes (PROs) in advanced breast cancer (ABC) treated with ribociclib (RIB) plus fulvestrant (FUL) as first-line (1L) and second-line (2L) therapy in MONALEESA-3 (ML-3) - Fasching, Peter; Neven, P.; Jerusalem, G.; Beck, J. T.; Chan, A.; De Laurentiis, M.; Bianchi, G. V.; Martin Jimenez, M.; Chia, S.; Gaur, A.; Sondhi, M.; Rodriguez-Lorenc, K.; et al. (ANNALS OF ONCOLOGY, 2020)
CRIS-Team WoS Importer:2020-06-26

Patient survival and tumor characteristics associated with CHEK2:p.I157T - findings from the Breast Cancer Association Consortium - Muranen, Taru A.; Blomqvist, Carl; Doerk, Thilo; Jakubowska, Anna; Heikkila, Paivi; Fagerholm, Rainer; Greco, Dario; Aittomaki, Kristiina; Bojesen, Stig E.; Shah, Mitul; Dunning, Alison M.; Rhenius, Valerie; et al. (Breast Cancer Research, 2016)
BACKGROUND: P.I157T is a CHEK2 missense mutation associated with a modest increase in breast cancer risk. Previously, another CHEK2 mutation, the protein truncating c.1100delC has been associated with poor prognosis of breast cancer patients. Here, we have investigated patient survival and characteristics of breast tumors of germ line p.I157T carriers. METHODS: We included in the analyses 26,801 European female breast cancer patients from 15 studies participating in the Breast Cancer Association Consortium. We analyzed the association between p.I157T and the clinico-pathological breast cancer characteristics by comparing the p.I157T carrier tumors to non-carrier and c.1100delC carrier tumors. Similarly, we investigated the p.I157T associated risk of early death, breast cancer-associated death, distant metastasis, locoregional relapse and second breast cancer using Cox proportional hazards models. Additionally, we explored the p.I157T-associated genomic gene expression profile using data from breast tumors of 183 Finnish female breast cancer patients (ten p.I157T carriers) (GEO: GSE24450). Differential gene expression analysis was performed using a moderated t test. Functional enrichment was investigated using the DAVID functional annotation tool and gene set enrichment analysis (GSEA). The tumors were classified into molecular subtypes according to the St Gallen 2013 criteria and the PAM50 gene expression signature. RESULTS: P.I157T was not associated with increased risk of early death, breast cancer-associated death or distant metastasis relapse, and there was a significant difference in prognosis associated with the two CHEK2 mutations, p.I157T and c.1100delC. Furthermore, p.I157T was associated with lobular histological type and clinico-pathological markers of good prognosis, such as ER and PR expression, low TP53 expression and low grade. Gene expression analysis suggested luminal A to be the most common subtype for p.I157T carriers and CDH1 (cadherin 1) target genes to be significantly enriched among genes, whose expression differed between p.I157T and non-carrier tumors. CONCLUSIONS: Our analyses suggest that there are fundamental differences in breast tumors of CHEK2:p.I157T and c.1100delC carriers. The poor prognosis associated with c.1100delC cannot be generalized to other CHEK2 mutations.
EVALuna2:32945

Pattern of invasion in stage I mucinous ovarian cancer is prognostic within 2-years of diagnosis - Meagher, Nicola; Koebel, Martin; Anderson, Lyndal; Tan, Adeline; Bolithon, Adelyn; Anglesio, Michael; Cohen, Paul; Crowe, Philip; Doherty, Jennifer; Fasching, Peter; Harris, Holly; Hogdall, Estrid; et al. (ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, 2021)
CRIS-Team WoS Importer:2021-09-24

Pattern of SMARCB1 (INI1) and SMARCA4 (BRG1) in poorly differentiated endometrioid adenocarcinoma of the uterus: analysis of a series with emphasis on a novel SMARCA4-deficient dedifferentiated rhabdoid variant - Strehl, Johanna D.; Wachter, David; Fiedler, Jutta; Heimerl, Engelbert; Beckmann, Matthias; Hartmann, Arndt; Agaimy, Abbas (Annals of Diagnostic Pathology, 2015)
The role of the switch/sucrose nonfermenting chromatin remodeling complex in the initiation and progression of cancer is emerging. In the female genital tract, only ovarian small cell carcinoma, hypercalcemic type harbors recurrent inactivating SMARCA4 mutations. Otherwise, only rare case reports documented SMARCB1 involvement in endometrial cancer. We analyzed 24 grade 3 uterine endometrioid adenocarcinomas and 2 undifferentiated carcinomas for immunohistochemical expression of SMARCB1 and SMARCA4. All tumors showed high-grade nuclear features with a predominance of solid growth pattern. All cases showed intact nuclear SMARCB1 expression in all tumor cells. However, 1 case of a 78-year-old woman showed complete loss of SMARCA4 in 90% of the tumor with retained expression in 10% of the tumor. The SMARCA4-intact component was a moderate-to-poorly differentiated endometrioid adenocarcinoma. The SMARCA4-deficient dominating component showed solid growth of highly anaplastic undifferentiated large cells with prominent rhabdoid features. None of the 25 SMARCA4-intact cases showed rhabdoid cell morphology. To our knowledge, this is the first systematic study of SMARCB1 and SMARCA4 expression in endometrioid adenocarcinoma of uterus and the first description of a novel SMARCA4-deficient variant of dedifferentiated/undifferentiated endometrial carcinoma. The presence of a differentiated SMARCA4-intact endometrioid component points to a novel pathway of dedifferentiation in endometrioid adenocarcinoma as a consequence of a "second hit." This case further underlines the close link between the "rhabdoid phenotype" and the SWI/SNF pathway.
EVALuna2:6700

Patterns and Trends of Herbal Medicine Use among Patients with Gynecologic Cancer - Theuser, Anna Katharin; Hack, Carolin; Fasching, Peter; Antoniadis, Sophia; Grasruck, Katharina; Wasner, Sonja; Knoll, Stefanie; Sievers, Hartwig; Beckmann, Matthias; Thiel, Falk C. (Geburtshilfe und Frauenheilkunde, 2021)
Background More and more information about complementary and integrative medicine is becoming available, especially among cancer patients. However, little is known about the use of herbal medicine by patients with gynecologic cancers. This study aimed to assess the use of herbal products by gynecologic cancer patients compared with healthy controls. Methods This cross-sectional study was conducted at the Department for Gynecology and Obstetrics of Erlangen University Hospital and included 201 patients with gynecologic cancer and 212 healthy controls. Use of herbal medicines was evaluated using a standardized questionnaire. Medical information on cancer patients was collected from hospital records. Group comparisons were done using a logistic regression model. Risk ratios were assessed using a Poisson regression model. Results Gynecologic cancer patients used herbal medicine significantly less often than healthy persons. 69% of gynecologic cancer patients and 81% of healthy participants reported using herbal products. 40% of cancer patients and 56% of healthy persons reported using plants for medicinal purposes. Motives of cancer patients for using herbal medicine included treatment of cancer-related symptoms. The major source of information for both groups was family and friends. Conclusions Although herbal medicine was used less by patients with gynecologic cancer, herbal products were used by both cancer patients and healthy individuals. To provide cancer patients with optimal therapy, oncologists should be informed about the herbal products used by their patients as this will allow them to take their patients' self-medication with herbal medicine into account. Counseling by oncologists on the use of herbal medicine should be encouraged.
CRIS-Team Scopus Importer:2021-07-02
Keywords: cancer; complementary and alternative medicine; gynecologic oncology; herbal medicine; integrative medicine

Pelvic Lymphadenectomy in Vulvar Cancer – Does it make sense? - Woelber, Linn; Bommert, Mareike; Prieske, Katharina; Fischer, Inger; Zu Eulenburg, Christine; Vettorazzi, Eik; Harter, Philipp; Jueckstock, Julia; Hilpert, Felix; De Gregorio, Niko; Iborra, Severine; Sehouli, Jalid; et al. (Geburtshilfe und Frauenheilkunde, 2020)
Since the publication of the updated German guideline in 2015, the recommendations for performing pelvic lymphadenectomy (LAE) in patients with vulvar cancer (VSCC) have changed considerably. The guideline recommends surgical lymph node staging in all patients with a higher risk of pelvic lymph node involvement. However, the current data do not allow the population at risk to be clearly defined, therefore, the indication for pelvic lymphadenectomy is still not clear. There are currently two published German patient populations who had pelvic LAE which can be used to investigate both the prognostic effect of histologically verified pelvic lymph node metastasis and the relation between inguinal and pelvic lymph node involvement. A total of 1618 patients with primary FIGO stage ≥ IB VSCC were included in the multicenter AGO CaRE-1 study (1998-2008), 70 of whom underwent pelvic LAE. During a retrospective single-center evaluation carried out at the University Medical Center Hamburg-Eppendorf (UKE), a total of 514 patients with primary VSCC treated between 1996-2018 were evaluated, 21 of whom underwent pelvic LAE. In both cohorts, around 80% of the patients who underwent pelvic LAE were inguinally node-positive, with a median number of three affected groin lymph nodes. There were no cases of pelvic lymph node metastasis without inguinal lymph node metastasis in either of the two cohorts. Between 33-35% of the inguinal node-positive patients also had pelvic lymph node metastasis; the median number of affected groin lymph nodes in these patients was high (> 4), and the maximum median diameter of the largest inguinal metastasis was > 40 mm in both cohorts. Pelvic lymph node staging and pelvic radiotherapy is therefore probably not necessary for the majority of node-positive patients with VSCC, as the relevant risk of pelvic lymph node involvement was primarily found in node-positive patients with high-grade disease. More, ideally prospective data collections are necessary to validate the relation between inguinal and pelvic lymph node involvement.
CRIS-Team Scopus Importer:2020-12-25
Keywords: lymph node metastasis; pelvic lymphadenectomy; prognosis; recurrence; vulvar cancer

Pembrolizumab for early triple-negative breast cancer - Schmid, P.; Cortes, J.; Pusztai, L.; McArthur, H.; Kümmel, S.; Bergh, J.; Denkert, C.; Park, Y. H.; Hui, R.; Harbeck, N.; Takahashi, M.; Foukakis, T.; et al. (New England Journal of Medicine, 2020)
Background: Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear. Methods: In this phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with previously untreated stage II or stage III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) every 3 weeks plus paclitaxel and carboplatin (784 patients; the pembrolizumab-chemotherapy group) or placebo every 3 weeks plus paclitaxel and carboplatin (390 patients; the placebo-chemotherapy group); the two groups then received an additional four cycles of pembrolizumab or placebo, and both groups received doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, the patients received adjuvant pembrolizumab or placebo every 3 weeks for up to nine cycles. The primary end points were a pathological complete response at the time of definitive surgery and event-free survival in the intention-to-treat population. Results: At the first interim analysis, among the first 602 patients who underwent randomization, the percentage of patients with a pathological complete response was 64.8% (95% confidence interval [CI], 59.9 to 69.5) in the pembrolizumab-chemotherapy group and 51.2% (95% CI, 44.1 to 58.3) in the placebo-chemotherapy group (estimated treatment difference, 13.6 percentage points; 95% CI, 5.4 to 21.8; P<0.001). After a median follow-up of 15.5 months (range, 2.7 to 25.0), 58 of 784 patients (7.4%) in the pembrolizumab-chemotherapy group and 46 of 390 patients (11.8%) in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause (hazard ratio, 0.63; 95% CI, 0.43 to 0.93). Across all treatment phases, the incidence of treatment-related adverse events of grade 3 or higher was 78.0% in the pembrolizumab-chemotherapy group and 73.0% in the placebo-chemotherapy group, including death in 0.4% (3 patients) and 0.3% (1 patient), respectively. Conclusions: Among patients with early triple-negative breast cancer, the percentage with a pathological complete response was significantly higher among those who received pembrolizumab plus neoadjuvant chemotherapy than among those who received placebo plus neoadjuvant chemotherapy.
CRIS-Team Scopus Importer:2020-03-17

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer – A single-arm phase II trial (NeoImmunoboost, AGO-B-041) - Fasching, Peter; Hein, Alexander; Kolberg, Hans Christian; Häberle, Lothar; Uhrig, Sabrina; Rübner, Matthias; Belleville, Erik; Hack, Carolin; Fehm, Tanja N.; Janni, Wolfang; Hartmann, Arndt; Erber, Ramona; et al. (European Journal of Cancer, 2023)
Background: Pembrolizumab is approved for the neoadjuvant/adjuvant treatment of early triple-negative breast cancer (TNBC) patients in combination with chemotherapy. The Keynote-522 trial used platinum chemotherapy. As neoadjuvant nab-paclitaxel (nP) is also highly effective in triple-negative breast cancer patients, this study investigates the response to nP-containing neoadjuvant chemotherapy in combination with pembrolizumab. Patients and methods: NeoImmunoboost (AGO-B-041/NCT03289819) is a multicenter, prospective single-arm phase II trial. Patients were treated with 12 weekly cycles of nP followed by four three-weekly cycles of epirubicin/cyclophosphamide. Pembrolizumab was given three-weekly in combination with these chemotherapies. The study was planned for 50 patients. After 25 patients, the study was amended to include a pre-chemotherapy single application of pembrolizumab. The primary aim was pathological complete response (pCR), and the secondary aims were safety and quality of life. Results: Of 50 included patients, 33 (66.0%; 95%confidence interval: 51.2%–78.8%) had a (ypT0/is ypN0) pCR. The pCR rate in the per-protocol population (n = 39) was 71.8% (95%confidence interval: 55.1%–85.0%). The most common adverse events of any grade were fatigue (58.5%), peripheral sensory neuropathy (54.7%) and neutropenia (52.8%). The pCR rate in the cohort of 27 patients with a pre-chemotherapy pembrolizumab dose was 59.3%, and 73.9% in the 23 patients without pre-chemotherapy dose. Conclusions: pCR rates after NACT with nP and anthracycline combined with pembrolizumab are encouraging. With acceptable side-effect profiles, this treatment might be a reasonable alternative to platinum-containing chemotherapy in cases of contraindications. However, without data from randomised trials and long-term follow up, platinum/anthracycline/taxane-based chemotherapy remains the standard combination chemotherapy for pembrolizumab.
CRIS-Team Scopus Importer:2023-03-24
Keywords: Neoadjuvant chemotherapy; PD-L1; Pembrolizumab; Triple-negative

Percent mammographic density and dense area as risk factors for breast cancer - Rauh, C.; Hack, Caroline; Häberle, Lothar; Hein, Alexander; Engel, Anne; Schrauder, Michael G.; Fasching, Peter; Jud, Sebastian; Ekici, Arif Bülent; Loehberg, C. R.; Meier-Meitinger, Martina; Ozan-Mergner, Sevil Julia; et al. (Geburtshilfe und Frauenheilkunde, 2012)
Purpose: Mammographic characteristics are known to be correlated to breast cancer risk. Percent mammographic density (PMD), as assessed by computer-assisted methods, is an established risk factor for breast cancer. Along with this assessment the absolute dense area (DA) of the breast is reported as well. Aim of this study was to assess the predictive value of DA concerning breast cancer risk in addition to other risk factors and in addition to PMD. Methods: We conducted a case control study with hospital-based patients with a diagnosis of invasive breast cancer and healthy women as controls. A total of 561 patients and 376 controls with available mammographic density were included into this study. We describe the differences concerning the common risk factors BMI, parital status, use of hormone replacement therapy (HRT) and menopause between cases and controls and estimate the odds ratios for PMD and DA, adjusted for the mentioned risk factors. Furthermore we compare the prediction models with each other to find out whether the addition of DA improves the model. Results: Mammographic density and DA were highly correlated with each other. Both variables were as well correlated to the commonly known risk factors with an expected direction and strength, however PMD (ρ = 0.56) was stronger correlated to BMI than DA (ρ = 0.11). The group of women within the highest quartil of PMD had an OR of 2.12 (95 % CI: 1.25-3.62). This could not be seen for the fourth quartile concerning DA. However the assessment of breast cancer risk could be improved by including DA in a prediction model in addition to common risk factors and PMD. Conclusions: The inclusion of the parameter DA into a prediction model for breast cancer in addition to established risk factors and PMD could improve the breast cancer risk assessment. As DA is measured together with PMD in the process of computer-assisted assessment of PMD it might be considered to include it as one additional breast cancer risk factor that is obtained from breast imaging. © Georg Thieme Verlag KG Stuttgart · New York.
CRIS-Team Scopus Importer:2021-07-19
Keywords: breast cancer; mammographic density; risk

Performance of Photon-Counting Breast Computed Tomography, Digital Mammography, and Digital Breast Tomosynthesis in Evaluating Breast Specimens - Rößler, Ann-Christin; Kalender, Willi Alfred; Kolditz, Daniel; Steiding, Christian; Ruth, Veikko; Preuss, Caroline; Peter, Sandra Christina; Brehm, Barbara; Hammon, Matthias; Schulz-Wendtland, Rüdiger; Wenkel, Evelyn (Academic Radiology, 2017)
This study compared a novel photon-counting breast computed tomography (pcBCT) system with digital mammography (DM) and digital breast tomosynthesis (DBT) systems. For this reason, surgical specimens were examined with all three techniques and rated by three observers.A total of 30 surgical specimens were investigated with DM, DBT, and pcBCT; the associated images were shown to three experienced radiologists. Findings (22 microcalcifications and 23 mass lesions) were recorded and compared to the results of the pathological examination. Sensitivity and specificity for detection of microcalcifications and lesions were calculated and displayed using receiver operating characteristic curves.Sensitivity for microcalcifications was 82% for DM, 70% for DBT, and 85% for pcBCT. Specificity for microcalcifications was 71% for DM, 75% for DBT, and 83% for pcBCT. Sensitivity for lesions was 45% for DM, 62% for DBT, and 65% for pcBCT. Specificity for lesions was 76% for DM, 62% for DBT, and 76% for pcBCT.pcBCT showed a comparable or superior performance compared to the clinically approved DM and DBT systems. Mass lesion detectability can be increased further by the use of contrast media.
EVALuna2:14619